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Niculescu AG, Mitache MM, Grumezescu AM, Chifiriuc MC, Mihai MM, Tantu MM, Tantu AC, Popa LG, Grigore GA, Cristian RE, Popa MI, Vrancianu CO. From Microbial Ecology to Clinical Challenges: The Respiratory Microbiome's Role in Antibiotic Resistance. Pathogens 2025; 14:355. [PMID: 40333133 PMCID: PMC12030467 DOI: 10.3390/pathogens14040355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 04/01/2025] [Accepted: 04/03/2025] [Indexed: 05/09/2025] Open
Abstract
Antibiotic resistance represents a growing public health threat, with airborne drug-resistant strains being especially alarming due to their ease of transmission and association with severe respiratory infections. The respiratory microbiome plays a pivotal role in maintaining respiratory health, influencing the dynamics of antibiotic resistance among airborne pathogenic microorganisms. In this context, this review proposes the exploration of the complex interplay between the respiratory microbiota and antimicrobial resistance, highlighting the implications of microbiome diversity in health and disease. Moreover, strategies to mitigate antibiotic resistance, including stewardship programs, alternatives to traditional antibiotics, probiotics, microbiota restoration techniques, and nanotechnology-based therapeutic interventions, are critically presented, setting an updated framework of current management options. Therefore, through a better understanding of respiratory microbiome roles in antibiotic resistance, alongside emerging therapeutic strategies, this paper aims to shed light on how the global health challenges posed by multi-drug-resistant pathogens can be addressed.
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Affiliation(s)
- Adelina-Gabriela Niculescu
- Department of Science and Engineering of Oxide Materials and Nanomaterials, National University of Science and Technology POLITEHNICA Bucharest, 011061 Bucharest, Romania; (A.-G.N.); (A.M.G.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050663 Bucharest, Romania; (G.A.G.)
| | - Mihaela Magdalena Mitache
- Department of Preclinical Disciplines, Faculty of Medicine, Titu Maiorescu University, 031593 Bucharest, Romania;
| | - Alexandru Mihai Grumezescu
- Department of Science and Engineering of Oxide Materials and Nanomaterials, National University of Science and Technology POLITEHNICA Bucharest, 011061 Bucharest, Romania; (A.-G.N.); (A.M.G.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050663 Bucharest, Romania; (G.A.G.)
| | - Mariana Carmen Chifiriuc
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050663 Bucharest, Romania; (G.A.G.)
- Microbiology-Immunology Department, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
- Biological Sciences Division, Romanian Academy, Calea Victoriei 125, Sector 1, 010071 Bucharest, Romania
| | - Mara Madalina Mihai
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- Department of Oncologic Dermatology, “Elias” University Emergency Hospital, 010024 Bucharest, Romania
| | - Monica Marilena Tantu
- Department of Medical Assistance and Physical Therapy, Pitesti University Center, Târgu din Vale 1, 110040 Pitești, Romania;
- Faculty of Science, Physical Education and Informatics, National University of Science and Technology, Politehnica, Splaiul Independenței 313, District 6, 060042 Bucharest, Romania
| | - Ana Catalina Tantu
- Doctoral School, University of Medicine and Pharmacy of Craiova, Petru Rareș 2, 200349 Craiova, Romania;
- Emergency Clinical County Hospital of Craiova, Tabaci 1, 200642 Craiova, Romania
| | - Loredana Gabriela Popa
- Microbiology Discipline II, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (M.I.P.)
| | - Georgiana Alexandra Grigore
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050663 Bucharest, Romania; (G.A.G.)
- Microbiology-Immunology Department, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
- National Institute of Research and Development for Biological Sciences, 296 Splaiul Independentei, District 6, 060031 Bucharest, Romania
| | - Roxana-Elena Cristian
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050663 Bucharest, Romania; (G.A.G.)
- National Institute of Research and Development for Biological Sciences, 296 Splaiul Independentei, District 6, 060031 Bucharest, Romania
| | - Mircea Ioan Popa
- Microbiology Discipline II, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (M.I.P.)
- Preclinical Testing Unit, Cantacuzino National Military Medical Institute for Research and Development, 050096 Bucharest, Romania
| | - Corneliu Ovidiu Vrancianu
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050663 Bucharest, Romania; (G.A.G.)
- National Institute of Research and Development for Biological Sciences, 296 Splaiul Independentei, District 6, 060031 Bucharest, Romania
- Doctoral School, Carol Davila University of Medicine and Pharmacy, Eroii Sanitari 8, District 5, 050474 Bucharest, Romania
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2
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Caselli L, Malmsten M. Combining functionalities-nanoarchitectonics for combatting bacterial infection. Adv Colloid Interface Sci 2025; 337:103385. [PMID: 39721197 DOI: 10.1016/j.cis.2024.103385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 12/28/2024]
Abstract
New antimicrobial and anti-inflammatory therapeutics are needed because of antibiotic resistance development and resulting complications such as inflammation, ultimately leading to septic shock. The antimicrobial effects of various nanoparticles (NPs) are currently attracting intensive research interest. Although various NPs display potent antimicrobial effects against strains resistant to conventional antibiotics, the therapeutic use of such materials is restricted by poor selectivity between bacteria and human cells, leading to adverse side effects. As a result, increasing research efforts during the last few years have focused on targeting NPs against bacteria and other components in the infection micro-environment. Examples of approaches explored include peptide-, protein- and nucleic acid-based NP coatings for bacterial membrane recognition, as well as NP conjugation with enzyme substrates or other moieties that respond to bacterial or other enzymes present in the infection micro-environment. In general, this study aims to add to the literature on the antimicrobial effects of nanomaterials by discussing surface modification strategies for targeting bacterial membranes and membrane components, as well as how such surface modifications can improve the antimicrobial effects of nanomaterials and simultaneously decrease toxicity towards human cells and tissues. In doing so, the biological effects observed are related throughout to the physico-chemical modes of action underlying such effects.
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Affiliation(s)
| | - Martin Malmsten
- Physical Chemistry 1, University of Lund, S-221 00 Lund, Sweden; Department of Pharmacy, University of Copenhagen, DK-2100 Copenhagen, Denmark.
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Qamar W, Gulia S, Athar M, Ahmad R, Imam MT, Chandra P, Singh BP, Haque R, Hassan MI, Rahman S. An insight into impact of nanomaterials toxicity on human health. PeerJ 2024; 12:e17807. [PMID: 39364370 PMCID: PMC11448750 DOI: 10.7717/peerj.17807] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 07/03/2024] [Indexed: 10/05/2024] Open
Abstract
In recent years, advances in nanotechnology have significantly influenced electronics manufacturing, industrial processes, and medical research. Various industries have seen a surge in the use of nanomaterials. However, several researchers have raised the alarm about the toxicological nature of nanomaterials, which appear to be quite different from their crude forms. This altered nature can be attributed to their unique physicochemical profile. They can adversely affect human health and the environment. Nanomaterials that have been released into the environment tend to accumulate over time and can cause a significant impact on the ecosystem and organisms with adverse health effects. Increased use of nanoparticles has led to increased human exposure in their daily lives, making them more vulnerable to nanoparticle toxicity. Because of their small size, nanomaterials can readily cross biological membranes and enter cells, tissues, and organs. Therefore, the effect of nanomaterials on the human environment is of particular concern. The toxicological effects of nanomaterials and their mechanisms of action are being researched worldwide. Technological advances also support monitoring new nanomaterials marketed for industrial and household purposes. It is a challenging area because of the exceptional physicochemical properties of nanomaterials. This updated review focuses on the diverse toxicological perspective of nanomaterials. We have discussed the use of different types of nanoparticles and their physiochemical properties responsible for toxicity, routes of exposure, bio-distribution, and mechanism of toxicity. The review also includes various in vivo and in vitro methods of assessing the toxicity of nanomaterials. Finally, this review will provide a detailed insight into nano material-induced toxicological response, which can be beneficial in designing safe and effective nanoparticles.
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Affiliation(s)
- Wajhul Qamar
- Department of Pharmacology and Toxicology and Central Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shweta Gulia
- Department of Biotechnology, Delhi Technological University, New Delhi, India
| | - Mohammad Athar
- Department of Medical Genetics, Umm Al-Qura University, Makkah, Saudi Arabia
- Science and Technology Unit, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Razi Ahmad
- Department of Chemistry, Indian Institute of Technology, Delhi, New Delhi, India
| | - Mohammad Tarique Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia
| | - Prakash Chandra
- Department of Biotechnology, Delhi Technological University, New Delhi, India
| | - Bhupendra Pratap Singh
- Department of Environmental Studies, Deshbandhu College, University of Delhi, New Delhi, India
| | - Rizwanul Haque
- Department of Biotechnology, Central University of South Bihar, Gaya, Bihar, India
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia University, New Delhi, India
| | - Shakilur Rahman
- Department of Medical Elementology and Toxicology, Jamia Hamdard University, New Delhi, India
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Mukherjee S, Verma A, Kong L, Rengan AK, Cahill DM. Advancements in Green Nanoparticle Technology: Focusing on the Treatment of Clinical Phytopathogens. Biomolecules 2024; 14:1082. [PMID: 39334849 PMCID: PMC11430415 DOI: 10.3390/biom14091082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 08/08/2024] [Accepted: 08/21/2024] [Indexed: 09/30/2024] Open
Abstract
Opportunistic pathogenic microbial infections pose a significant danger to human health, which forces people to use riskier, more expensive, and less effective drugs compared to traditional treatments. These may be attributed to several factors, such as overusing antibiotics in medicine and lack of sanitization in hospital settings. In this context, researchers are looking for new options to combat this worrying condition and find a solution. Nanoparticles are currently being utilized in the pharmaceutical sector; however, there is a persistent worry regarding their potential danger to human health due to the usage of toxic chemicals, which makes the utilization of nanoparticles highly hazardous to eukaryotic cells. Multiple nanoparticle-based techniques are now being developed, offering essential understanding regarding the synthesis of components that play a crucial role in producing anti-microbial nanotherapeutic pharmaceuticals. In this regard, green nanoparticles are considered less hazardous than other forms, providing potential options for avoiding the extensive harm to the human microbiome that is prevalent with existing procedures. This review article aims to comprehensively assess the current state of knowledge on green nanoparticles related to antibiotic activity as well as their potential to assist antibiotics in treating opportunistic clinical phytopathogenic illnesses.
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Affiliation(s)
- Sunny Mukherjee
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502284, Telangana, India
- Institute for Frontier Materials, Deakin University, Geelong, VIC 3216, Australia
| | - Anamika Verma
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502284, Telangana, India
| | - Lingxue Kong
- Institute for Frontier Materials, Deakin University, Geelong, VIC 3216, Australia
| | - Aravind Kumar Rengan
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502284, Telangana, India
| | - David Miles Cahill
- School of Life and Environmental Sciences, Deakin University, Waurn Ponds, VIC 3216, Australia
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5
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Khatana K, Gupta A, Ghosal A, Dey P, Zafar F, Srivastava A, Verma P. In silico identification and validation of phenolic lipids as potential inhibitor against bacterial and viral strains. J Biomol Struct Dyn 2024; 42:2525-2538. [PMID: 37211872 DOI: 10.1080/07391102.2023.2212811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 04/16/2023] [Indexed: 05/23/2023]
Abstract
The recurrence of coronavirus disease and bacterial resistant strains has drawn attention to naturally occurring bioactive molecules that can demonstrate broad-spectrum efficacy against bacteria as well as viral strains. The drug-like abilities of naturally available "anacardic acids" (AA) and their derivatives against different bacterial and viral protein targets through in-silico tools were explored. Three viral protein targets [P DB: 6Y2E (SARS-CoV-2), 1AT3 (Herpes) and 2VSM (Nipah)] and four bacterial protein targets [P DB: 2VF5 (Escherichia coli), 2VEG (Streptococcus pneumoniae), 1JIJ (Staphylococcus aureus) and 1KZN (E. coli)] were selected to evaluate the activity of bioactive AA molecules. The potential ability to inhibit the progression of microbes has been discussed based on the structure, functionality and interaction ability of these molecules on the selected protein targets for multi-disease remediation. The number of interactions, full-fitness value and energy of the ligand-target system were determined from the docked structure in SwissDock and Autodock Vina. In order to compare the efficacy of these active derivatives to that of commonly used drugs against bacteria and viruses, a few of the selected molecules were subjected to 100 ns long MD simulations. It was found that the phenolic groups and alkyl chains of AA derivatives are more likely to bind with microbial targets, that could be responsible for the improved activity against these targets. The results suggest that the proposed AA derivatives have demonstrated potential to become active drug ingredients against microbial protein targets. Further, experimental investigations are essential for clinical verification of the drug-like abilities of AA derivatives.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Kavita Khatana
- Department of Chemical Engineering, School of Engineering, Shiv Nadar Institutions of Eminence Deemed to be University, Greater Noida, India
| | - Anjali Gupta
- School of Basic and Applied Science, Galgotias University, Greater Noida, India
| | - Anujit Ghosal
- Department of Chemistry, Jamia Millia Islamia, New Delhi, India
- Department of Food and Human Nutritional Sciences, The University of Manitoba, Winnipeg, MB, Canada
- Richardson Centre for Functional Foods and Nutraceuticals, The University of Manitoba, Winnipeg, MB, Canada
| | - Pinki Dey
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Fahmina Zafar
- Department of Chemistry, Jamia Millia Islamia, New Delhi, India
| | | | - Priya Verma
- Department of Physics, University of Lucknow, Lucknow, India
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6
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Alavi M, Nokhodchi A. Micro- and nanoformulations of antibiotics against Brucella. Drug Discov Today 2023; 28:103809. [PMID: 37923166 DOI: 10.1016/j.drudis.2023.103809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 10/24/2023] [Accepted: 10/27/2023] [Indexed: 11/07/2023]
Abstract
Brucellosis, a zoonotic intracellular bacterial infection primarily transmitted through the consumption of unpasteurized milk from infected animals, remains a challenging condition to clinically control. This is mainly because of the limited effectiveness of conventional antibiotics in targeting intracellular Brucella. Micro- and nanoformulations of antibiotics, whether used as a mono- or combination therapy, have the potential to reduce the antibiotic doses required and treatment duration. Extensive research has been conducted on various organic, semiorganic, and inorganic nanomaterials with different morphologies, such as nanoparticles (NPs), nanotubes, nanowires, and nanobelts. Metal/metal oxide, lipidic, polymeric, and carbonic NPs have been widely explored to overcome the limitations of traditional formulations. In this review, we discuss the advances and challenges of these novel formulations based on recent investigations.
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Affiliation(s)
- Mehran Alavi
- Department of Biological Science, Faculty of Science, University of Kurdistan, Sanandaj, Kurdistan, Iran.
| | - Ali Nokhodchi
- School of Life Sciences, University of Sussex, Brighton, UK; Lupin Research Inc, Lupin Pharmaceuticals, Coral Springs, FL, USA; Daru Vira Iranian Pharmaceutical Group, Isfahan, Iran.
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7
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Serna N, López-Laguna H, Aceituno P, Rojas-Peña M, Parladé E, Voltà-Durán E, Martínez-Torró C, Sánchez JM, Di Somma A, Carratalá JV, Livieri AL, Ferrer-Miralles N, Vázquez E, Unzueta U, Roher N, Villaverde A. Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation. Pharmaceutics 2023; 15:2632. [PMID: 38004610 PMCID: PMC10674355 DOI: 10.3390/pharmaceutics15112632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 10/31/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023] Open
Abstract
Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.
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Affiliation(s)
- Naroa Serna
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Hèctor López-Laguna
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Patricia Aceituno
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Biologia Cel·lular, Fisiologia Animal i Immunologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - Mauricio Rojas-Peña
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Biologia Cel·lular, Fisiologia Animal i Immunologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - Eloi Parladé
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Eric Voltà-Durán
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Carlos Martínez-Torró
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Julieta M. Sánchez
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
- Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT), (CONICET-Universidad Nacional de Córdoba), ICTA, FCEFyN, UNC. Av. Velez Sarsfield 1611, Córdoba X 5016GCA, Argentina
| | - Angela Di Somma
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
| | - Jose Vicente Carratalá
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Andrea L. Livieri
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
| | - Neus Ferrer-Miralles
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Esther Vázquez
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
| | - Ugutz Unzueta
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
- Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain
| | - Nerea Roher
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
- Departament de Biologia Cel·lular, Fisiologia Animal i Immunologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
| | - Antonio Villaverde
- Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; (N.S.); (P.A.); (M.R.-P.); (E.P.); (E.V.-D.); (C.M.-T.); (J.M.S.); (A.D.S.); (J.V.C.); (A.L.L.); (N.F.-M.); (E.V.); (N.R.)
- Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Barcelona, Spain
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8
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Antropenko A, Caruso F, Fernandez-Trillo P. Stimuli-Responsive Delivery of Antimicrobial Peptides Using Polyelectrolyte Complexes. Macromol Biosci 2023; 23:e2300123. [PMID: 37449448 DOI: 10.1002/mabi.202300123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 06/27/2023] [Accepted: 07/06/2023] [Indexed: 07/18/2023]
Abstract
Antimicrobial peptides (AMPs) are antibiotics with the potential to address antimicrobial resistance. However, their translation to the clinic is hampered by issues such as off-target toxicity and low stability in biological media. Stimuli-responsive delivery from polyelectrolyte complexes offers a simple avenue to address these limitations, wherein delivery is triggered by changes occurring during microbial infection. The review first provides an overview of pH-responsive delivery, which exploits the intrinsic pH-responsive nature of polyelectrolytes as a mechanism to deliver these antimicrobials. The examples included illustrate the challenges faced when developing these systems, in particular balancing antimicrobial efficacy and stability, and the potential of this approach to prepare switchable surfaces or nanoparticles for intracellular delivery. The review subsequently highlights the use of other stimuli associated with microbial infection, such as the expression of degrading enzymes or changes in temperature. Polyelectrolyte complexes with dual stimuli-response based on pH and temperature are also discussed. Finally, the review presents a summary and an outlook of the challenges and opportunities faced by this field. This review is expected to encourage researchers to develop stimuli-responsive polyelectrolyte complexes that increase the stability of AMPs while providing targeted delivery, and thereby facilitate the translation of these antimicrobials.
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Affiliation(s)
- Alexander Antropenko
- School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
- Department of Chemical Engineering, The University of Melbourne, Parkville, VIC, 3010, Australia
| | - Frank Caruso
- Department of Chemical Engineering, The University of Melbourne, Parkville, VIC, 3010, Australia
| | - Paco Fernandez-Trillo
- School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
- Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
- Departamento de Química, Facultade de Ciencias and Centro de Investigacións Cientı́ficas Avanzadas (CICA), Universidade da Coruña, A Coruña, 15071, Spain
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9
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Gupta J, Quadros M, Momin M. Mesoporous silica nanoparticles: Synthesis and multifaceted functionalization for controlled drug delivery. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023]
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10
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Geng Z, Cao Z, Liu J. Recent advances in targeted antibacterial therapy basing on nanomaterials. EXPLORATION (BEIJING, CHINA) 2023; 3:20210117. [PMID: 37323620 PMCID: PMC10191045 DOI: 10.1002/exp.20210117] [Citation(s) in RCA: 89] [Impact Index Per Article: 44.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 05/19/2022] [Indexed: 06/17/2023]
Abstract
Bacterial infection has become one of the leading causes of death worldwide, particularly in low-income countries. Despite the fact that antibiotics have provided successful management in bacterial infections, the long-term overconsumption and abuse of antibiotics has contributed to the emergence of multidrug resistant bacteria. To address this challenge, nanomaterials with intrinsic antibacterial properties or that serve as drug carriers have been substantially developed as an alternative to fight against bacterial infection. Systematically and deeply understanding the antibacterial mechanisms of nanomaterials is extremely important for designing new therapeutics. Recently, nanomaterials-mediated targeted bacteria depletion in either a passive or active manner is one of the most promising approaches for antibacterial treatment by increasing local concentration around bacterial cells to enhance inhibitory activity and reduce side effects. Passive targeting approach is widely explored by searching nanomaterial-based alternatives to antibiotics, while active targeting strategy relies on biomimetic or biomolecular surface feature that can selectively recognize targeted bacteria. In this review article, we summarize the recent developments in the field of targeted antibacterial therapy based on nanomaterials, which will promote more innovative thinking focusing on the treatment of multidrug-resistant bacteria.
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Affiliation(s)
- Zhongmin Geng
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
- The Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdaoChina
- Qingdao Cancer InstituteQingdao UniversityQingdaoChina
| | - Zhenping Cao
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Jinyao Liu
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
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11
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Feng W, Chittò M, Moriarty TF, Li G, Wang X. Targeted Drug Delivery Systems for Eliminating Intracellular Bacteria. Macromol Biosci 2023; 23:e2200311. [PMID: 36189899 DOI: 10.1002/mabi.202200311] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/08/2022] [Indexed: 01/19/2023]
Abstract
The intracellular survival of pathogenic bacteria requires a range of survival strategies and virulence factors. These infections are a significant clinical challenge, wherein treatment frequently fails because of poor antibiotic penetration, stability, and retention in host cells. Drug delivery systems (DDSs) are promising tools to overcome these shortcomings and enhance the efficacy of antibiotic therapy. In this review, the classification and the mechanisms of intracellular bacterial persistence are elaborated. Furthermore, the systematic design strategies applied to DDSs to eliminate intracellular bacteria are also described, and the strategies used for internalization, intracellular activation, bacterial targeting, and immune enhancement are highlighted. Finally, this overview provides guidance for constructing functionalized DDSs to effectively eliminate intracellular bacteria.
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Affiliation(s)
- Wenli Feng
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.,AO Research Institute Davos, Davos, 7270, Switzerland
| | - Marco Chittò
- AO Research Institute Davos, Davos, 7270, Switzerland
| | | | - Guofeng Li
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Xing Wang
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
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12
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Quaternary Ammonium-Tethered Phenylboronic Acids Appended Supramolecular Nanomicelles as a Promising Bacteria Targeting Carrier for Nitric Oxide Delivery. Polymers (Basel) 2022; 14:polym14204451. [PMID: 36298029 PMCID: PMC9611690 DOI: 10.3390/polym14204451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/13/2022] [Accepted: 10/19/2022] [Indexed: 11/05/2022] Open
Abstract
The delivery of drugs to focal sites is a central goal and a key challenge in the development of nanomedicine carriers. This strategy can improve the selectivity and bioavailability of the drug while reducing its toxicity. To ensure the specific release of nitric oxide at the site of a bacterial infection without damaging the surrounding normal tissue, we designed a host-guest molecule containing a host molecule with a target moiety and a nitric oxide donor to release nitric oxide. The boronic acid group in the structure of this nanoparticle interacts strongly and specifically with the surface of E. coli. In addition, the quaternary amine salt can interact electrostatically with bacteria, indicating a large number of negatively charged cell membranes; altering the molecular structure of the cell membrane; increasing the permeability of the cell membrane; and causing cytoplasmic diffusion and cell lysis, resulting in lethal activity against most bacteria. The synthesised molecules were characterised by 1H NMR and mass spectrometry. The strong specific interaction of the boronic acid moiety with the surface of E. coli and the electrostatic interaction of the quaternary amine salt with the cell membrane were confirmed by antibacterial experiments on molecules with and without the targeting moiety. The targeting group-modified micelles enhanced the antibacterial effect of the micelles very effectively through specific interactions and electrostatic interactions. In addition, in vitro skin wound healing experiments also confirmed the targeting and antimicrobial effect of micelles. These results suggest that the specific release of nitric oxide at the site of bacterial infection is an important guide to further address the emergence of antibiotic-resistant strains of bacteria.
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13
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Wang YF, Zhou Y, Sun J, Wang X, Jia Y, Ge K, Yan Y, Dawson KA, Guo S, Zhang J, Liang XJ. The Yin and Yang of the protein corona on the delivery journey of nanoparticles. NANO RESEARCH 2022; 16:715-734. [PMID: 36156906 PMCID: PMC9483491 DOI: 10.1007/s12274-022-4849-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/30/2022] [Accepted: 08/01/2022] [Indexed: 06/12/2023]
Abstract
Nanoparticles-based drug delivery systems have attracted significant attention in biomedical fields because they can deliver loaded cargoes to the target site in a controlled manner. However, tremendous challenges must still be overcome to reach the expected targeting and therapeutic efficacy in vivo. These challenges mainly arise because the interaction between nanoparticles and biological systems is complex and dynamic and is influenced by the physicochemical properties of the nanoparticles and the heterogeneity of biological systems. Importantly, once the nanoparticles are injected into the blood, a protein corona will inevitably form on the surface. The protein corona creates a new biological identity which plays a vital role in mediating the bio-nano interaction and determining the ultimate results. Thus, it is essential to understand how the protein corona affects the delivery journey of nanoparticles in vivo and what we can do to exploit the protein corona for better delivery efficiency. In this review, we first summarize the fundamental impact of the protein corona on the delivery journey of nanoparticles. Next, we emphasize the strategies that have been developed for tailoring and exploiting the protein corona to improve the transportation behavior of nanoparticles in vivo. Finally, we highlight what we need to do as a next step towards better understanding and exploitation of the protein corona. We hope these insights into the "Yin and Yang" effect of the protein corona will have profound implications for understanding the role of the protein corona in a wide range of nanoparticles.
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Affiliation(s)
- Yi-Feng Wang
- Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260 China
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190 China
| | - Yaxin Zhou
- Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China
| | - JiaBei Sun
- China National Institute of Food and Drug Control, Beijing, 100061 China
| | - Xiaotong Wang
- Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002 China
| | - Yaru Jia
- Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002 China
| | - Kun Ge
- Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002 China
| | - Yan Yan
- Centre for BioNano Interactions, School of Chemistry, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, D04V1W8 Ireland
| | - Kenneth A. Dawson
- Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260 China
- Centre for BioNano Interactions, School of Chemistry, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, D04V1W8 Ireland
| | - Shutao Guo
- Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China
| | - Jinchao Zhang
- Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002 China
| | - Xing-Jie Liang
- Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260 China
- Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190 China
- Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002 China
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14
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Bhattacharjee R, Dey T, Kumar L, Kar S, Sarkar R, Ghorai M, Malik S, Jha NK, Vellingiri B, Kesari KK, Pérez de la Lastra JM, Dey A. Cellular landscaping of cisplatin resistance in cervical cancer. Biomed Pharmacother 2022; 153:113345. [PMID: 35810692 DOI: 10.1016/j.biopha.2022.113345] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/22/2022] [Accepted: 06/24/2022] [Indexed: 12/11/2022] Open
Abstract
Cervical cancer (CC) caused by human papillomavirus (HPV) is one of the largest causes of malignancies in women worldwide. Cisplatin is one of the widely used drugs for the treatment of CC is rendered ineffective owing to drug resistance. This review highlights the cause of resistance and the mechanism of cisplatin resistance cells in CC to develop therapeutic ventures and strategies that could be utilized to overcome the aforementioned issue. These strategies would include the application of nanocarries, miRNA, CRIPSR/Cas system, and chemotherapeutics in synergy with cisplatin to not only overcome the issues of drug resistance but also enhance its anti-cancer efficiency. Moreover, we have also discussed the signaling network of cisplatin resistance cells in CC that would provide insights to develop therapeutic target sites and inhibitors. Furthermore, we have discussed the role of CC metabolism on cisplatin resistance cells and the physical and biological factors affecting the tumor microenvironments.
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Affiliation(s)
- Rahul Bhattacharjee
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar 751024, Odisha, India
| | - Tanima Dey
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar 751024, Odisha, India
| | - Lamha Kumar
- School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram 695551, Kerala, India
| | - Sulagna Kar
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar 751024, Odisha, India
| | - Ritayan Sarkar
- KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar 751024, Odisha, India
| | - Mimosa Ghorai
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, West Bengal, India
| | - Sumira Malik
- Amity Institute of Biotechnology, Amity University Jharkhand, Ranchi, Jharkhand 834001, India
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering and Technology (SET), Sharda University, Greater Noida, Uttar Pradesh 201310, India; Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun 248007, India; Department of Biotechnology Engineering and Food Technology, Chandigarh University, Mohali 140413, India.
| | - Balachandar Vellingiri
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641-046, India
| | - Kavindra Kumar Kesari
- Department of Applied Physics, School of Science, Aalto University, Espoo 00076, Finland; Department of Bio-products and Bio-systems, School of Chemical Engineering, Aalto University, Espoo 00076, Finland
| | - José M Pérez de la Lastra
- Biotechnology of Macromolecules, Instituto de Productos Naturales y Agrobiología, IPNA (CSIC), Avda. Astrofísico Francisco Sánchez, 3, 38206 San Cristóbal de la Laguna (Santa Cruz de Tenerife), Spain.
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, West Bengal, India.
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15
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Anand U, Carpena M, Kowalska-Góralska M, Garcia-Perez P, Sunita K, Bontempi E, Dey A, Prieto MA, Proćków J, Simal-Gandara J. Safer plant-based nanoparticles for combating antibiotic resistance in bacteria: A comprehensive review on its potential applications, recent advances, and future perspective. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 821:153472. [PMID: 35093375 DOI: 10.1016/j.scitotenv.2022.153472] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/22/2022] [Accepted: 01/24/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Antibiotic resistance is one of the current threats to human health, forcing the use of drugs that are more noxious, costlier, and with low efficiency. There are several causes behind antibiotic resistance, including over-prescription of antibiotics in both humans and livestock. In this scenario, researchers are shifting to new alternatives to fight back this concerning situation. SCOPE AND APPROACH Nanoparticles have emerged as new tools that can be used to combat deadly bacterial infections directly or indirectly to overcome antibiotic resistance. Although nanoparticles are being used in the pharmaceutical industry, there is a constant concern about their toxicity toward human health because of the involvement of well-known toxic chemicals (i.e., sodium/potassium borohydride) making their use very risky for eukaryotic cells. KEY FINDINGS AND CONCLUSIONS Multiple nanoparticle-based approaches to counter bacterial infections, providing crucial insight into the design of elements that play critical roles in the creation of antimicrobial nanotherapeutic drugs, are currently underway. In this context, plant-based nanoparticles will be less toxic than many other forms, which constitute promising candidates to avoid widespread damage to the microbiome associated with current practices. This article aims to review the actual knowledge on plant-based nanoparticle products for antibiotic resistance and the possible replacement of antibiotics to treat multidrug-resistant bacterial infections.
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Affiliation(s)
- Uttpal Anand
- Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
| | - M Carpena
- Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, E32004 Ourense, Spain.
| | - Monika Kowalska-Góralska
- Department of Limnology and Fisheries, Institute of Animal Husbandry and Breeding, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland.
| | - P Garcia-Perez
- Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, E32004 Ourense, Spain.
| | - Kumari Sunita
- Department of Botany, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, Uttar Pradesh 273009, India
| | - Elza Bontempi
- INSTM and Chemistry for Technologies Laboratory, Department of Mechanical and Industrial Engineering, University of Brescia, Via Branze, 38, 25123 Brescia, Italy.
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, West Bengal, India.
| | - Miguel A Prieto
- Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, E32004 Ourense, Spain.
| | - Jarosław Proćków
- Department of Plant Biology, Institute of Environmental Biology, Wrocław University of Environmental and Life Sciences, ul. Kożuchowska 7a, 51-631 Wrocław, Poland.
| | - Jesus Simal-Gandara
- Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, E32004 Ourense, Spain.
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16
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Tuchin VV, Genina EA, Tuchina ES, Svetlakova AV, Svenskaya YI. Optical clearing of tissues: Issues of antimicrobial phototherapy and drug delivery. Adv Drug Deliv Rev 2022; 180:114037. [PMID: 34752842 DOI: 10.1016/j.addr.2021.114037] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 09/23/2021] [Accepted: 10/28/2021] [Indexed: 02/08/2023]
Abstract
This review presents principles and novelties in the field of tissue optical clearing (TOC) technology, as well as application for optical monitoring of drug delivery and effective antimicrobial phototherapy. TOC is based on altering the optical properties of tissue through the introduction of immersion optical cleaning agents (OCA), which impregnate the tissue of interest. We also analyze various methods and kinetics of delivery of photodynamic agents, nanoantibiotics and their mixtures with OCAs into the tissue depth in the context of antimicrobial and antifungal phototherapy. In vitro and in vivo studies of antimicrobial phototherapies, such as photodynamic, photothermal plasmonic and photocatalytic, are summarized, and the prospects of a new TOC technology for effective killing of pathogens are discussed.
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17
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Fadaka AO, Sibuyi NRS, Madiehe AM, Meyer M. Nanotechnology-Based Delivery Systems for Antimicrobial Peptides. Pharmaceutics 2021; 13:pharmaceutics13111795. [PMID: 34834210 PMCID: PMC8620809 DOI: 10.3390/pharmaceutics13111795] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 12/14/2022] Open
Abstract
Antimicrobial resistance (AMR) is a significant threat to global health. The conventional antibiotic pool has been depleted, forcing the investigation of novel and alternative antimicrobial strategies. Antimicrobial peptides (AMPs) have shown potential as alternative diagnostic and therapeutic agents in biomedical applications. To date, over 3000 AMPs have been identified, but only a fraction of these have been approved for clinical trials. Their clinical applications are limited to topical application due to their systemic toxicity, susceptibility to protease degradation, short half-life, and rapid renal clearance. To circumvent these challenges and improve AMP’s efficacy, different approaches such as peptide chemical modifications and the development of AMP delivery systems have been employed. Nanomaterials have been shown to improve the activity of antimicrobial drugs by providing support and synergistic effect against pathogenic microbes. This paper describes the role of nanotechnology in the targeted delivery of AMPs, and some of the nano-based delivery strategies for AMPs are discussed with a clear focus on metallic nanoparticle (MNP) formulations.
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Affiliation(s)
| | | | | | - Mervin Meyer
- Correspondence: (A.O.F.); (N.R.S.S.); (A.M.M.); (M.M.)
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18
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Marrazzo P, Pizzuti V, Zia S, Sargenti A, Gazzola D, Roda B, Bonsi L, Alviano F. Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome. Antibiotics (Basel) 2021; 10:750. [PMID: 34206190 PMCID: PMC8300685 DOI: 10.3390/antibiotics10070750] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/11/2021] [Accepted: 06/18/2021] [Indexed: 02/06/2023] Open
Abstract
Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advantageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms.
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Affiliation(s)
- Pasquale Marrazzo
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy; (V.P.); (L.B.); (F.A.)
| | - Valeria Pizzuti
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy; (V.P.); (L.B.); (F.A.)
| | - Silvia Zia
- Stem Sel S.r.l., 40127 Bologna, Italy; (S.Z.); (B.R.)
| | | | - Daniele Gazzola
- Cell Dynamics i.S.r.l., 40129 Bologna, Italy; (A.S.); (D.G.)
| | - Barbara Roda
- Stem Sel S.r.l., 40127 Bologna, Italy; (S.Z.); (B.R.)
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy
| | - Laura Bonsi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy; (V.P.); (L.B.); (F.A.)
| | - Francesco Alviano
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy; (V.P.); (L.B.); (F.A.)
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19
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Spirescu VA, Chircov C, Grumezescu AM, Andronescu E. Polymeric Nanoparticles for Antimicrobial Therapies: An Up-To-Date Overview. Polymers (Basel) 2021; 13:724. [PMID: 33673451 PMCID: PMC7956825 DOI: 10.3390/polym13050724] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 02/23/2021] [Accepted: 02/24/2021] [Indexed: 12/20/2022] Open
Abstract
Despite the many advancements in the pharmaceutical and medical fields and the development of numerous antimicrobial drugs aimed to suppress and destroy pathogenic microorganisms, infectious diseases still represent a major health threat affecting millions of lives daily. In addition to the limitations of antimicrobial drugs associated with low transportation rate, water solubility, oral bioavailability and stability, inefficient drug targeting, considerable toxicity, and limited patient compliance, the major cause for their inefficiency is the antimicrobial resistance of microorganisms. In this context, the risk of a pre-antibiotic era is a real possibility. For this reason, the research focus has shifted toward the discovery and development of novel and alternative antimicrobial agents that could overcome the challenges associated with conventional drugs. Nanotechnology is a possible alternative, as there is significant evidence of the broad-spectrum antimicrobial activity of nanomaterials and nanoparticles in particular. Moreover, owing to their considerable advantages regarding their efficient cargo dissolving, entrapment, encapsulation, or surface attachment, the possibility of forming antimicrobial groups for specific targeting and destruction, biocompatibility and biodegradability, low toxicity, and synergistic therapy, polymeric nanoparticles have received considerable attention as potential antimicrobial drug delivery agents. In this context, the aim of this paper is to provide an up-to-date overview of the most recent studies investigating polymeric nanoparticles designed for antimicrobial therapies, describing both their targeting strategies and their effects.
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Affiliation(s)
- Vera Alexandra Spirescu
- Department of Science and Engineering of Oxide Materials and Nanomaterials, University Politehnica of Bucharest, 011061 Bucharest, Romania; (V.A.S.); (C.C.); (E.A.)
| | - Cristina Chircov
- Department of Science and Engineering of Oxide Materials and Nanomaterials, University Politehnica of Bucharest, 011061 Bucharest, Romania; (V.A.S.); (C.C.); (E.A.)
| | - Alexandru Mihai Grumezescu
- Department of Science and Engineering of Oxide Materials and Nanomaterials, University Politehnica of Bucharest, 011061 Bucharest, Romania; (V.A.S.); (C.C.); (E.A.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
| | - Ecaterina Andronescu
- Department of Science and Engineering of Oxide Materials and Nanomaterials, University Politehnica of Bucharest, 011061 Bucharest, Romania; (V.A.S.); (C.C.); (E.A.)
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20
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Juárez-Maldonado A, Tortella G, Rubilar O, Fincheira P, Benavides-Mendoza A. Biostimulation and toxicity: The magnitude of the impact of nanomaterials in microorganisms and plants. J Adv Res 2021; 31:113-126. [PMID: 34194836 PMCID: PMC8240115 DOI: 10.1016/j.jare.2020.12.011] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 12/22/2020] [Accepted: 12/26/2020] [Indexed: 01/02/2023] Open
Abstract
Background Biostimulation and toxicity constitute the continuous response spectrum of a biological organism against physicochemical or biological factors. Among the environmental agents capable of inducing biostimulation or toxicity are nanomaterials. On the < 100 nm scale, nanomaterials impose both physical effects resulting from the core’s and corona’s surface properties, and chemical effects related to the core’s composition and the corona’s functional groups. Aim of Review The purpose of this review is to describe the impact of nanomaterials on microorganisms and plants, considering two of the most studied physical and chemical properties: size and concentration. Key Scientific Concepts of Review Using a graphical analysis, the presence of a continuous biostimulation-toxicity spectrum is shown considering different biological responses. In microorganisms, the results showed high susceptibility to nanomaterials. Simultaneously, in plants, a hormetic response was found related to nanomaterials concentration and, in a few cases, a positive response in the smaller nanomaterials when these were applied at a higher level. With the above, it is concluded that: (1) microorganisms are more susceptible to nanomaterials than plants, (2) practically all nanomaterials seem to induce responses from biostimulation to toxicity in plants, and (3) the kind of response observed will depend in a complex way on the nanomateriaĺs physical and chemical characteristics, of the biological species with which they interact, and of the form and route of application and on the nature of the medium -soil, soil pore water, and biological surfaces- where the interaction occurs.
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Affiliation(s)
| | - Gonzalo Tortella
- Centro de Excelencia en Investigación Biotecnológica Aplicada al Medio Ambiente (CIBAMA), Facultad de Ingeniería y Ciencias, Universidad de La Frontera, 4811230 Temuco, Chile
| | - Olga Rubilar
- Centro de Excelencia en Investigación Biotecnológica Aplicada al Medio Ambiente (CIBAMA), Facultad de Ingeniería y Ciencias, Universidad de La Frontera, 4811230 Temuco, Chile
| | - Paola Fincheira
- Centro de Excelencia en Investigación Biotecnológica Aplicada al Medio Ambiente (CIBAMA), Facultad de Ingeniería y Ciencias, Universidad de La Frontera, 4811230 Temuco, Chile
| | - Adalberto Benavides-Mendoza
- Departamento de Horticultura, Universidad Autónoma Agraria Antonio Narro, 25315 Saltillo, Mexico
- Corresponding author.
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21
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Carvalho GC, Sábio RM, de Cássia Ribeiro T, Monteiro AS, Pereira DV, Ribeiro SJL, Chorilli M. Highlights in Mesoporous Silica Nanoparticles as a Multifunctional Controlled Drug Delivery Nanoplatform for Infectious Diseases Treatment. Pharm Res 2020; 37:191. [PMID: 32895867 PMCID: PMC7476752 DOI: 10.1007/s11095-020-02917-6] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/25/2020] [Indexed: 12/19/2022]
Abstract
Infectious diseases are a major global concern being responsible for high morbidity and mortality mainly due to the development and enhancement of multidrug-resistant microorganisms exposing the fragility of medicines and vaccines commonly used to these treatments. Taking into account the scarcity of effective formulation to treat infectious diseases, nanotechnology offers a vast possibility of ground-breaking platforms to design new treatment through smart nanostructures for drug delivery purposes. Among the available nanosystems, mesoporous silica nanoparticles (MSNs) stand out due their multifunctionality, biocompatibility and tunable properties make them emerging and actual nanocarriers for specific and controlled drug release. Considering the high demand for diseases prevention and treatment, this review exploits the MSNs fabrication and their behavior in biological media besides highlighting the most of strategies to explore the wide MSNs functionality as engineered, smart and effective controlled drug release nanovehicles for infectious diseases treatment. Graphical Abstract Schematic representation of multifunctional MSNs-based nanoplatforms for infectious diseases treatment.
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Affiliation(s)
- Gabriela Corrêa Carvalho
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, 14800-903, Brazil
| | - Rafael Miguel Sábio
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, 14800-903, Brazil.
| | - Tais de Cássia Ribeiro
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, 14800-903, Brazil
| | - Andreia Sofia Monteiro
- Institute of Chemistry, São Paulo State University (UNESP), Araraquara, 14800-060, Brazil
| | | | | | - Marlus Chorilli
- School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, 14800-903, Brazil
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