Recently, cancer therapy has witnessed remarkable advancements with a growing focus on precision medicine and targeted drug delivery strategies. The application of anionic polysaccharides has gained traction in various drug delivery systems. Anionic polysaccharides have emerged as promising delivery carriers in cancer therapy and theranostics, offering numerous advantages such as biocompatibility, low toxicity, and the ability to encapsulate and deliver therapeutic agents to tumor sites with high specificity. This review underscores the significance of anionic polysaccharides as essential components of the evolving landscape of cancer therapy and theranostics. These polymers can be tailored to carry a wide range of therapeutic cargo, including chemotherapeutic agents, nucleic acids, and imaging agents. Their negative charge enables electrostatic interactions with positively charged drugs and facilitates the formation of stable nanoparticles, liposomes, or hydrogels for controlled drug release. Additionally, their hydrophilic nature aids in prolonging circulation time, reducing drug degradation, and minimizing off-target effects. Besides, some of them could act as targeting agents or therapeutic compounds that lead to improved therapeutic performance. This review offers valuable information for researchers, clinicians, and biomedical engineers. It provides insights into the recent progress in the applications of anionic polysaccharide-based delivery platforms in cancer theranostics to transform patient outcomes.

Surgical resection and postoperative adjuvant chemotherapy have enhanced the outlook for breast cancer patients. However, tumor relapse and serious side effects of chemotherapy continue to impact patients' quality of life. Designing injectable composite hydrogel made of biodegradable polymers providing sustained release of antiangiogenic and chemotherapeutic agents might play a vital role in elimination of cancer cells. In this regard, we developed dextran based composite hydrogel incorporating doxorubicin-loaded dual-sensitive pH-redox nanogels (DOX-DSNG) and combretastatin A4 (CA4) loaded liposomes which undergo rapid disassembly in cancer cells. CA4 prevents tubulin polymerization and thus inhibits angiogenesis by binding to vascular endothelial tubulin. The results showed that DOX-DSNGs were negatively charged and 144.8 ± 0.85 nm in size. Besides, the size of CA4 loaded liposomes were 102.35 ± 4.22 nm and were negatively charged. Encapsulation efficiency of DOX-DSNGs and CA4 loaded liposomes were 100 % and 89 %, respectively. After loading into the hydrogel structure, doxorubicin and CA4 were gradually released from the composite hydrogel for up to 21 days. DOX-DSNGs and CA4 loaded liposomes showed a dose-dependent cytotoxic effect against 4 T1 breast cancer cells. Thereafter, the anti-neoplastic effect and survival study of the composite hydrogel was evaluated in vivo in tumor-bearing mice. The composite hydrogel significantly reduced tumor volume (from 116 mm3 to 38 mm3) with negligible organ damage, while showed lower cardiotoxicity in 28 days. In conclusion, our results revealed that injectable composite dextran-based hydrogel incorporated with DOX-DSNG and CA4 loaded liposomes could be used as an efficient delivery platform for combination therapies in treatment of solid tumors.

Cancer represents a significant societal, public health, and economic challenge. Conventional chemotherapy is based on systemic administration; however, it has current limitations, including poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, and the development of multiple drug resistance. These factors underscore the need for innovative strategies to enhance drug delivery directly to tumours. However, local treatment also presents significant challenges, including the penetration of the drug through endothelial layers, tissue density in the tumour microenvironment, tumour interstitial fluid pressure, physiological conditions within the tumour, and permanence at the site of action. Nanotechnology represents a promising alternative for addressing these challenges. This narrative review elucidates the potential of nanostructured formulations for local cancer treatment, providing illustrative examples and an analysis of the advantages and challenges associated with this approach. Among the nanoformulations developed for the local treatment of breast, bladder, colorectal, oral, and melanoma cancer, polymeric nanoparticles, liposomes, lipid nanoparticles, and nanohydrogels have demonstrated particular efficacy. These systems permit mucoadhesion and enhanced tissue penetration, thereby increasing the drug concentration at the tumour site (bioavailability) and consequently improving anti-tumour efficacy and potentially reducing adverse effects. In addition to studies indicating chemotherapy, nanocarriers can be used as a theranostic approach and in combination with irradiation methods.

Combination therapy using chemo-photothermal therapy (chemo-PTT) shows great efficacy toward tumor ablation in preclinical studies. Besides, lipopolymersomes as a hybrid nanocarriers, integrate advantages of liposomes and polymersomes in a single platform in order to provide tremendous biocompatibility, biodegradability, noteworthy loading efficacy for both hydrophobic and hydrophilic drugs with adjustable drug release and high stability. In this study, a multipurpose lipopolymersome was fabricated for guided chemotherapy-PTT and NIR-imaging of melanoma. A lipopolymerosomal hybrid nanovesicle consisting of equal molar ratio of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) diblock copolymer (molar ratio 1:1) was fabricated. The nanoparticulate system was prepared through film rehydration technique for encapsulation of doxorubicin (DOX) and indocyanine green (ICG) to form DOX-ICG-LP platform. At the next stage, AS1411 DNA aptamer was conjugated to the surface of lipopolymersome (Apt-DOX-ICG-LP) for selective delivery. The sizes of DOX-ICG-LP and Apt-DOX-ICG-LP were obtained through DLS analysis (61.0 ± 6 and 74 ± 5, respectively). Near Infrared-responsive release pattern of the prepared lipopolymersome was verified in vitro. The formulated platform showed efficient photothermal conversion, and superior stability with acceptable encapsulation efficiency. Consistent with the in vitro studies, NIR-responsive lipopolymersome exhibited significantly higher cellular toxicity for Chemo-PTT versus single anti-cancer treatment. Moreover, superlative tumor shrinkage with favorable survival profile were attained in B16F10 tumor-bearing mice received Apt-DOX-ICG-LP and irradiated with 808 nm laser compared to those treated with either DOX-ICG-LP or Apt-DOX-ICG-LP without laser irradiation. The diagnostic capability of Apt-DOX-ICG-LP was addressed using in vivo NIR imaging, 6 and 24 h post-intravenous administration. The results indicated desirable feature of an established targeted theranostic capability of Apt-DOX-ICG-LP for both diagnostics and dual chemo-PTT of melanoma.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

Achieving targeted, customized, and combination therapies with clarity of the involved molecular pathways is crucial in the treatment as well as overcoming multidrug resistance (MDR) in cancer. Nanotechnology has emerged as an innovative and promising approach to address the problem of drug resistance. Developing nano-formulation-based therapies using therapeutic agents poses a synergistic effect to overcome MDR in cancer. In this review, we aimed to highlight the important pathways involved in the progression of MDR in cancer mediated through nanotechnology-based approaches that have been employed to circumvent them in recent years. Here, we also discussed the potential use of marine metabolites to treat MDR in cancer, utilizing active drug-targeting nanomedicine-based techniques to enhance selective drug accumulation in cancer cells. The discussion also provides future insights for developing complex targeted, multistage responsive nanomedical drug delivery systems for effective cancer treatments. We propose more combinational studies and their validation for the possible marine-based nanoformulations for future development.

To improve the anticancer properties of elesclomol (ELC), targeted theranostic nanoparticles (NPs; APT-PEG-Au-MMNPs@ELC) were designed to increase the selectivity of the drug delivery system (DDS).

ELC was synthesized and entrapped in the open porous structure of magnetic mesoporous silica nanoparticles (MMNPs). The pore entrance of MMNPs was then blocked using gold gatekeepers. Finally, the external surfaces of the particles were grafted with functional polyethylene glycol (PEG) and EpCAM aptamer to generate biocompatible and targeted NPs. In the next step, the physicochemical properties of prepared NPs were fully evaluated and their anticancer potential was evaluated both in vitro and in vivo.

The targeted NPs were successfully synthesized with a final size diameter of 81.13 ± 7.41 nm. The results indicated a pH-dependent release pattern, which sustained for 72 h despite an initial rapid release. Upon exposure to APT-PEG-Au-MMNPs@ELC, higher cytotoxicity was observed in human prostate cancer cells (PC-3) as compared with control Chinese hamster ovary (CHO) cells, indicating higher specificity of targeted NPs against EpCAM-positive cancerous cells. Moreover, APT-PEG-Au-MMNPs@ELC could induce apoptosis in PC-3 cells. In vivo results on a PC-3 xenograft tumor model demonstrated that targeted NPs could significantly inhibit tumor growth and diminish severe side effects of ELC, compared to the free drug.

Collectively, APT-PEG-Au-MMNPs@ELC could be considered a promising theranostic platform for the targeted delivery of ELC to improve its therapeutic effects in prostate cancer.

Colorectal cancer (CRC) is a common malignant tumor, and traditional treatments include surgical resection and radiotherapy. However, local recurrence, distal metastasis, and intestinal obstruction are significant problems. Oral nano-formulation is a promising treatment strategy for CRC. This study introduces physiological and environmental factors, the main challenges of CRC treatment, and the need for a novel oral colon-targeted drug delivery system (OCDDS). This study reviews the research progress of controlled-release, responsive, magnetic, targeted, and other oral nano-formulations in the direction of CRC treatment, in addition to the advantages of oral colon-targeted nano-formulations and concerns about the oral delivery of related therapeutic agents to inspire related research.

Mesenchymal stem cell membrane (MSCM)-coated biomimetic doxorubicin-loaded hollow gold nanoparticles were fabricated and decorated with MUC1 aptamer in order to provide smart theranostic platform. The prepared targeted nanoscale biomimetic platform was extensively characterized and evaluated in terms of selective delivery of DOX and CT-scan imaging. The fabricated system illustrated spherical morphology with 118 nm in diameter. Doxorubicin was loaded into the hollow gold nanoparticles through physical absorption technique with encapsulation efficiency and loading content of 77%±10 and 31%±4, respectively. The in vitro release profile demonstrated that the designed platform could respond to acidic environment, pH 5.5 and release 50% of the encapsulated doxorubicin during 48 h, while 14% of the encapsulated doxorubicin was released in physiological condition, pH 7.4 up to 48 h. The in vitro cytotoxicity experiments on 4T1 as MUC1 positive cell line illustrated that the targeted formulation could significantly increase mortality at 0.468 and 0.23 µg/ml of equivalent DOX concentration compared to non-targeted formulation while this cytotoxicity was not observed in CHO as MUC1 negative cell line. Furthermore, in vivo experiments showed high tumor accumulation of the targeted formulation even 24 h after intravenous injection which induced effective tumor growth suppression against 4T1 tumor bearing mice. On the other hand, existence of hollow gold in this platform provided CT scan imaging capability of the tumor tissue in 4T1 tumor bearing mice up to 24 h post-administration. The obtained results indicated that the designed paradigm are promising and safe theranostic system for fighting against metastatic breast cancer.

DNA nanotechnology has significantly advanced and might be used in biomedical applications, drug delivery, and cancer treatment during the past few decades. DNA nanomaterials are widely used in biomedical research involving biosensing, bioimaging, and drug delivery since they are remarkably addressable and biocompatible. Gradually, modified nucleic acids have begun to be employed to construct multifunctional DNA nanostructures with a variety of architectural designs. Aptamers are single-stranded nucleic acids (both DNAs and RNAs) capable of self-pairing to acquire secondary structure and of specifically binding with the target. Diagnosis and tumor therapy are prospective fields in which aptamers can be applied. Many DNA nanomaterials with three-dimensional structures have been studied as drug delivery systems for different anticancer medications or gene therapy agents. Different chemical alterations can be employed to construct a wide range of modified DNA nanostructures. Chemically altered DNA-based nanomaterials are useful for drug delivery because of their improved stability and inclusion of functional groups. In this work, the most common oligonucleotide nanomaterials were reviewed as modern drug delivery systems in tumor cells.

Cancer stem cells (CSCs) are believed to be the main cause of chemotherapy resistance and tumor relapse. Various therapeutic strategies to eliminate CSCs have been developed recently. Aptamers, also called "chemical antibodies", can specifically bind with their molecular targets through special tertiary structures. The advantages of aptamers, such as lower immunogenicity and smaller size, make them superior to conventional antibodies. Therefore, aptamers have been used widely as targeting ligands for CSC-targeted therapeutic strategies in different tumor types. To date, various therapeutic cargoes have been conjugated to aptamers to kill CSCs, such as chemotherapy drugs, small interfering RNAs, and microRNAs. Aptamer-based targeted therapies for CSCs have made great progress in recent years, especially the development of multifunctional aptamer-based therapeutic strategies. Besides, cell-systematic evolution of ligands by exponential enrichment has been applied to screen new aptamers that might have a higher binding ability for CSCs. In this review, we focus on recent advances and introduce some new modalities of aptamer-drug conjugates against CSCs. Some considerations of the advantages and limitations of different aptamer-based targeted therapies for CSCs are also discussed.

Peptosomes, as a vesicular polypeptide-based system and a versatile carrier for co-delivery of hydrophilic and hydrophobic materials, provide great delivery opportunities due to the intrinsic biocompatibility and biodegradability of the polypeptides backbone. In the current study, a novel poly(L-glutamic acid)-block-polylactic acid di-block copolymer (PGA-PLA) was synthesized in two steps. Firstly, γ-benzyl L-glutamate-N-carboxy anhydride (BLG-NCA) and 3,6-dimethyl-1,4-dioxane-2,5-dione were polymerized using N-hexylamine and benzyl alcohol as initiators to produce poly(γ-benzyl L-glutamate (PBLG) and polylactic acid. Then, PBLG was deprotected to produce PGA. Secondly, PGA was conjugated to the benzyl-PLGA to fabricate PGA-PLA diblock copolymer. The synthesized diblock copolymer was used for the encapsulation of doxorubicin, as hydrophilic anticancer and ultra-small superparamagnetic iron oxide nanoparticles (USPIONs) as hydrophobic contrast agent within aqueous core and bilayer of vesicular peptosome, respectively via double emulsion method. The prepared peptosomes (Pep@USPIONs-DOX) controlled the release of DOX (<15 % of the encapsulated DOX release up to 240 h of incubation at the physiological conditions) while increasing the stability and solubility of the hydrophobic USPIONs. Then, AS1411 DNA aptamer was decorated on the surface of the PGA-PLA peptosomes (Apt-Pep@USPIONs-DOX). The prepared targeted and non-targeted platforms showed spherical morphology with hydrodynamic sizes of 265 ± 52 and 229 ± 44 nm respectively. In vitro cellular cytotoxicity and cellular uptake were studied in nucleolin positive (4T1) and nucleolin negative (CHO) cell lines. Cellular uptake of the targeted formulation was greater than that of non-targeted peptosome, while cellular internalization of these peptosomes was identical in CHO cells. Moreover, targeted peptosomes showed greater toxicity than non-targeted peptosome in 4T1 cell line. The prepared theranostic targeted peptosomes demonstrated improved capability in terms of survival rate, biodistribution, tumor suppression efficiency, and MR imaging in the 4T1 tumor-bearing mice.

Cancer is a complex disease associated with a combination of abnormal physiological process and exhibiting dysfunctions in multiple systems. To provide effective treatment and diagnosis for cancer, current treatment strategies simultaneously focus on various tumor targets. Based on the rapid development of nanotechnology, nanocarriers have been shown to exhibit excellent potential for cancer therapy. Compared with nanoparticles with single functions, multifunctional nanoparticles are believed to be more aggressive and potent in the context of tumor targeting. However, the development of multifunctional nanoparticles is not simply an upgraded version of the original function, but involves a sophisticated system with a proper backbone, optimized modification sites, simple preparation method, and efficient function integration. Despite this, many well-designed multifunctional nanoparticles with promising therapeutic potential have emerged recently. Here, to give a detailed understanding and analyzation of the currently developed multifunctional nanoparticles, their platform structures with organic or inorganic backbones were systemically generalized. We emphasized on the functionalization and modification strategies, which provide additional functions to the nanoparticle. We also discussed the application combination strategies that were involved in the development of nanoformulations with functional crosstalk. This review thus provides an overview of the construction strategies and application advances of multifunctional nanoparticles.

In recent years, the functionalization of mesoporous silica nanoparticles (MSNs) with different types of responsive pore gatekeepers have shown great potential for the formulation of drug delivery systems (DDS) with minimal premature leakage and site-specific controlled release. New nanotechnological approaches have been developed with the objective of utilizing natural biopolymers as smart materials in drug delivery applications. Natural biopolymers are sensitive to various physicochemical and biological stimuli and are endowed with intrinsic biodegradability, biocompatibility, and low immunogenicity. Their use as biocompatible smart coatings has extensively been investigated in the last few years. This review summarizes the MSNs coating procedures with natural polysaccharides and protein-based biopolymers, focusing on their application as responsive materials to endogenous stimuli. Biopolymer-coated MSNs, which conjugate the nanocarrier features of mesoporous silica with the biocompatibility and controlled delivery provided by natural coatings, have shown promising therapeutic outcomes and the potential to emerge as valuable candidates for the selective treatment of various diseases.

Designing and fabrication of theranostic systems based on nanoscale gaseous vesicular systems, named nanobubbles (NBs), attracted enormous interest in recent years. Biomimetic vesicular platform (V-RBC-M) can improve the pharmacokinetics of the prepared platform due to augmented circulation half-life, desirable biodegradability and biocompatibility and reduced immunogenicity.

V-RBC-M were used for the encapsulation of lipophilic camptothecin (CPT) in the bilayer of vesicles through top-down method, followed by filling the core of V-RBC-M with inert SF6 gas to fabricate NBs with ultrasonic contrast enhancement capability (SF6-NB-CPT). In the next step, targeted NBs were formed via decoration of MUC1 aptamer on the surface of NBs (Apt-SF6-NB-CPT).

The designed bio-NBs indicated high encapsulation efficiency and the sustained release of CPT at pH 7.4. In vitro study demonstrated higher cellular uptake and cytotoxicity of Apt-SF6-NB-CPT compared to SF6-NB-CPT in MUC1-overexpressing cells (C26). In vivo antitumor efficacy of the prepared NBs on C26 bearing BALB/c mice showed greater therapeutic efficacy and survival rate for Apt-SF6-NB-CPT. In this regard, SF6-NB-CPT showed 58% tumor growth suppression while Apt-SF6-NB-CPT system provided 95% tumor growth suppression. Furthermore, echogenic capability of SF6-NB-CPT was demonstrated through in vitro and in vivo ultrasonic imaging.

Our finding demonstrated that the prepared targeted NBs are a promising theranostic platform with effective therapeutic and diagnotic potentials.

Undesirable side effects and multidrug tolerance are the main holdbacks to the treatment of cancer in conventional chemotherapy. Fortunately, targeted drug delivery can improve the enrichment of drugs at the target site and reduce toxicity to normal tissues and cells. A targeted drug delivery system is usually composed of a nanocarrier and a targeting component. The targeting component is called a "ligand". Aptamers have high target affinity and specificity, which are identified as attractive and promising ligands. Therefore, aptamers have potential application in the development of smart targeting systems. For instance, aptamers are able to efficiently recognize tumor markers such as nucleolin, mucin, and epidermal growth factor receptor (EGFR). Besides, aptamers can also identify glycoproteins on the surface of tumor cells. Thus, the aptamer-mediated targeted drug delivery system has received extensive attention in the application of cancer therapy. This article reviews the application of aptamers as smart ligands for targeted drug delivery in cancer therapy. Special interest is focused on aptamers as smart ligands, aptamer-conjugated nanocarriers, aptamer targeting strategy for tumor microenvironment (TME), and aptamers that are specified to crucial cancer biomarkers for targeted drug delivery.

Nanomaterials are developing rapidly in the medical field, bringing new hope for treating various refractory diseases. Among them, polymer nanomaterials, with their excellent properties, have been used to treat various diseases, such as malignant tumors, diabetes, and nervous system diseases. Gastrointestinal cancer is among the cancers with the highest morbidity and mortality worldwide. Cancer stem cells are believed to play an important role in the occurrence and development of tumors. This article summarizes the characteristics of gastrointestinal cancer stem cells and reviews the latest research progress in treating gastrointestinal malignant tumors using polymer nanoparticles to target cancer stem cells. In addition, the review article highlights the potential of polymer nanoparticles in targeting gastrointestinal cancer stem cells.

Targeted drug-delivery systems are a growing research topic in tumor treatment. In recent years, mesoporous silica nanoparticles (MSNs) have been extensively studied and applied in noninvasive and biocompatible drug-delivery systems for tumor therapy due to their outstanding advantages, which include high surface area, large pore volume, tunable pore size, easy surface modification and stable framework. The advances in the application of MSNs for anticancer drug targeting are covered and highlighted in this review, and the challenges and prospects of MSN-based targeted drug-delivery systems are discussed. This review provides new insights for researchers interested in targeted drug-delivery systems against cancer.

Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced drug efflux, cell death inhibition, and various other molecular and cellular mechanisms, are responsible for the development of resistance against anticancer agents. Drug resistance can also depend on cellular autophagic and hypoxic status. The expression of drug-resistant genes and the regulatory mechanisms that determine drug resistance are also discussed. Methods to circumvent MDR, including immunoprevention, the use of microparticles and nanomedicine might result in better strategies for fighting cancer.

Nanoscale coordination polymers (nCP) have exhibited a great potential in designing of the theranostic platforms in the latest years. However, they have low selectivity for cancerous tissues and require to be modified for becoming effective cancer therapeutics. In this study, a novel nanoscale pH and redox-responsive coordination polymer with high selectivity was synthesized.

The nCP was synthesized by iron(III) chloride and dithiodiglycolic acid. After loading the prepared nCP with doxorubicin (DOX), nCP was coated with an amphiphilic copolymer composed of α-tocopheryl succinate-polyethylene glycol (VEP). Next, AS1411 aptamer was decorated on the VEP shell of the DOX-loaded nCP (Apt-VEP-nCP@DOX) to provide a guided drug delivery platform.

The prepared platform demonstrated high DOX loading capacity and pH and redox-responsive DOX release. Apt-VEP-nCP@DOX displayed greater DOX internalization and toxicity towards breast cancer cells of 4T1 and MCF7 compared with that of non-targeted VEP-nCP@DOX. Also, the intravenous injection of Apt-VEP-nCP@DOX (a single dose) considerably suppressed the 4T1 tumor growth in vivo. Moreover, Apt-VEP-nCP@DOX showed outstanding magnetic resonance (MR) imaging capability for 4T1 adenocarcinoma diagnosis in ectopic 4T1 tumor model in mice.

The developed innovative intelligent Apt-VEP-nCP@DOX could serve as a safe and biocompatible theranostic platform appropriate for further translational purposes against breast cancer.

Dendritic fibrous nanosilica (DFNS) is a suitable nano-carrier for loading pesticides with radially oriented pores and a large surface area. The microemulsion method is standard method to prepare DFNS, and 1-pentanol is taken to replace cyclohexane as an oil solvent due to its high stability and nontoxic property. The results showed that the volume ratio of 1-pentanol (oil) to water (O/W) and the molar ratio of hexadecyltrimethylammonium bromide (CTAB) to tetraethylorthosilicate (TEOS) had effected on morphology and adsorption properties of DFNS in the water-CTAB-1-pentanol-ethanol-trimethylbenzene (TMB) microemulsion system. DFNS with bicontinuous concentric lamellar morphologies can be synthesized in this microemulsion at the meager O/W volume ratio (0.025-0.045). It features a tight mesoporous structure with a thin dendritic fibrous in 0.03 to 0.04 O/W volume ratio. The particle sizes, surface areas, and porosity of DFNS were positively correlated with the addition of the silica precursor TEOS. The size of DFNS increased from 123 to about 220 nm with the CTAB/TEOS molar ratio decreasing from 0.119 to 0.050. When the molar ratio of CTAB to TEOS  = 0.119, DFNS has a smaller particle size (123 nm) with a larger surface area and abundant honeycomb mesopores; the low O/W volume ratio strategy provides theoretical support for the industrialization development of DFNS and nano-pesticides, which plays a profound role in promoting the sustainable development of pesticide reduction, efficiency and green agriculture.

Small-molecular drugs are extensively used in cancer therapy, while they have issues of nonspecific distribution and consequent side effects. Nanomedicines that incorporate chemotherapeutic drugs have been developed to enhance the therapeutic efficacy of these drugs and reduce their side effects. One of the promising strategies is to prepare nanomedicines by harnessing the unique tumor microenvironment (TME).

The TME contains numerous cell types that specifically express specific antibodies on the surface including tumor vascular endothelial cells, tumor-associated adipocytes, tumor-associated fibroblasts, tumor-associated immune cells and cancer stem cells. The physicochemical environment is characterized with a low pH, hypoxia, and a high redox potential resulting from tumor-specific metabolism. The intelligent nanomedicines can be categorized into two groups: the first group which is rapidly responsive to extracellular chemical/biological factors in the TME and the second one which actively and/or specifically targets cellular components in the TME.

In this paper, we review recent progress of nanomedicines by harnessing the TME and illustrate the principles and advantages of different strategies for designing nanomedicines, which are of great significance for exploring novel nanomedicines or translating current nanomedicines into clinical practice. We will discuss the challenges and prospects of preparing nanomedicines to utilize or alter the TME for achieving effective, safe anticancer treatment.

Mesoporous silica nanoparticles (MSNs) have been well-researched in the design and fabrication of advanced drug delivery systems (DDSs) due to their advantages such as good biocompatibility, large specific surface area and pore volume for drug loading, easily surface modification, adjusted size and good thermal/chemical stability. For MSN-based DDSs, gate materials are also necessary. And natural polysaccharides, one kind of the most abundant natural resource, have been widely applied as the "gatekeepers" in MSN-based DDSs. Polysaccharides are cheap and rich in sources with good biocompatibility, and some of them have important biological functions. In this review article, polysaccharides including chitosan, hyaluronic acid, sodium alginate and dextran, et al. are briefly introduced. And the preparation processes and properties such as controlled drug release, cancer targeting and disease diagnosis of functional polysaccharide/MSN-based DDSs are discussed.

This study aimed to synthesize a star-shaped micelle using 3-azido-2,2-bis(azidomethyl)propan-1-ol (pentaerythritol triazide) core, as an initiator for the synthesis of three-arm polylactic acid (PLA) block. Then, the ends of the PLA arms were converted to PLA triazide followed by conjugation to the three alkyne-PEG-maleamide through click reaction. The maleamide ends were available for coupling with sulfhydryl-modified DNA aptamer against epithelial cell adhesion molecule in order to offer targeted delivery of encapsulated drug, camptothecin to the site of action. The successful synthesis of the star-shaped polymers was confirmed via¹HNMR. Hydrophobic anti-cancer drug, camptothecin was encapsulated into the micelles core implementing solvent switching method providing loading content (LC%) and encapsulation efficiency (EE%) of 3.7 ± 0.4 and 73.7 ± 8.2, respectively. The size of both non-targeted and aptamer-targeted micelles was determined to be 154 and 192 nm, respectively with polydispersity index below 0.3. In vitro drug release evaluation at 37 °C, pH 7.4 showed a controlled release pattern for camptothecin during 72 h. In vitro cytotoxicity of the prepared non-targeted and targeted micelles was carried out on human colorectal adenocarcinoma (HT29) and mouse colon carcinoma (C26) as EpCAM positive cell lines and Chinese hamster ovary (CHO) as EpCAM negative cell line. The results verified significantly higher cytotoxicity of the targeted micelles on HT29 and C26 cell lines, while no obvious difference was observed between targeted and non-targeted formulation on CHO cell line. The in vivo therapeutic efficiency investigation on BALB/c C26 tumor-bearing mice showed superior capability of the targeted formulation on tumor suppression and survival rate of the treated mice. The developed platform exhibited excellent characteristics to diminish camptothecin drawbacks and its adverse effects while considerably increasing its therapeutic index.

Due to the high frequency and mortality of breast cancer, developing efficient targeted drug delivery systems for frightening against this malignancy is among cancer research priorities. The aim of this study was to synthesize a targeted micellar formulation of docetaxel (DTX) using DTX, folic acid (FA) and polyethylene glycol (PEG) conjugates as building blocks. In the current study, two therapeutic polymers consisting of FA-PEG-DTX and PEG-DTX conjugates were synthesized and implemented to form folate-targeted and non-targeted micelles. Dissipative particle dynamics (DPD) method was used to simulate the behavior of the nanoparticle. The anti-cancer drug, DTX was loaded in to the micelles via solvent switching method in order to increase its solubility and stability. The cytotoxicity of the targeted and non-targeted formulations was evaluated against 4T1 and CHO cell lines. In vivo therapeutic efficiency was studied using ectopic tumor model of metastatic breast cancer, 4T1, in Female BALB/c mice. The successful synthesis of therapeutic polymers, FA-PEG-DTX and PEG-DTX were confirmed implementing ¹HNMR spectral analysis. The size of DTX-loaded non-targeted and targeted micelles were 176.3 ± 8.3 and 181 ± 10.1 nm with PDI of 0.23 and 0.17, respectively. Loading efficiencies of DTX in non-targeted and targeted micelles were obtained to be 85% and 82%, respectively. In vitro release study at pH = 7.4 and pH = 5.4 showed a controlled and continuous drug release for both formulations, that was faster at pH = 5.4 (100% drug release within 120 h) than at pH = 7.4 (80% drug release within 150 h). The targeted formulation showed a significant higher cytotoxicity against 4T1 breast cancer cells (high expression of folate receptor) within the range of 12.5 to 200 μg/mL in comparison with no-targeted one. However, there was no significant difference between the cytotoxicity of the targeted and non-targeted formulations against CHO cell line as low-expressed cell line. In accordance with in vitro investigation, in vivo studies verified the ideal anti-tumor efficacy of the targeted formulation compared to Taxotere and non-targeted formulation. Based on the obtained data, FA-targeted DTX-loaded nano-micelles significantly increased the therapeutic efficacy of DTX and therefore can be considered as a new potent platform for breast cancer chemotherapy.

In this study, a dual-receptor doxorubicin-targeted delivery system based on mesoporous silica nanoparticles (MSNs) modified with mucine-1 and ATP aptamers (DOX@MSNs-Apts) was developed. An amine-modified mucine-1 (MUC1) aptamer was covalently anchored on the surface of carboxyl-functionalized MSNs. Then, ATP aptamers (ATP1 and ATP2 aptamers) were immobilized on the surface of MSNs through partial hybridization with the MUC1 aptamer by forming a Y-shaped DNA structure on the MSNs surface (DOX@MSNs-Apts) as a gatekeeper. The developed DOX@MSNs-Apts exhibited high DOX loading capacity. In addition, it indicated an ATP-responsive feature, leading to the release of DOX in the environment with high ATP concentration (10 mM), similar to the intracellular environment of tumor cells. This property demonstrated that anticancer drug (DOX) could be entrapped inside the nanocarrier with nearly no leakage in blood and a very low concentration of ATP (1 μM). It was found that after the internalization of DOX@MSNs-MUC1 by cancer cells via the MUC1 receptor-mediated endocytosis, the ATP aptamers left the surface of the nanocarrier, allowing for rapid DOX release. DOX@MSNs-Apts indicated higher cellular uptake in MCF-7 and C26 cancer cells (MUC1+), rather than CHO cells (MUC1-). The in vitro cytotoxicity and the in vivo antitumor efficacy of DOX@MSNs-Apts showed greater cytotoxicity than the nanoparticles decorated with scrambled ATP aptamers (DOX@MSNs-Apts scrambled) in C26 and MCF-7 cell lines (MUC1+). The biodistribution and in vivo anticancer efficacy on the C26 tumor bearing mice indicated that the DOX@MSNs-Apts had a higher tumor accumulation and superior tumor growth inhibitory effect compared to free DOX and their scrambled aptamers, DOX@MSNs-Apts scrambled. Overall, the obtained results indicated that the prepared smart platform could reveal new insights into the treatment of cancer.

The development of drug resistance is one of the main causes of cancer treatment failure. This phenomenon occurs very frequently in different types of cancer, including colon and pancreatic cancers. However, the underlying molecular mechanisms are not fully understood. In recent years, nanomedicine has improved the delivery and efficacy of drugs, and has decreased their side effects. In addition, it has allowed to design drugs capable of avoiding certain resistance mechanisms of tumors. In this article, we review the main resistance mechanisms in colon and pancreatic cancers, along with the most relevant strategies offered by nanodrugs to overcome this obstacle. These strategies include the inhibition of efflux pumps, the use of specific targets, the development of nanomedicines affecting the environment of cancer-specific tissues, the modulation of DNA repair mechanisms or RNA (miRNA), and specific approaches to damage cancer stem cells, among others. This review aims to illustrate how advanced nanoformulations, including polymeric conjugates, micelles, dendrimers, liposomes, metallic and carbon-based nanoparticles, are allowing to overcome one of the main limitations in the treatment of colon and pancreatic cancers. The future development of nanomedicine opens new horizons for cancer treatment.

Inorganic/organic hybrid nanosystems have been increasingly developed for their versatility and efficacy at overcoming obstacles not readily surmounted by nonhybridized counterparts. Currently, hybrid nanosystems are implemented for gene therapy, drug delivery, and phototherapy in addition to tissue regeneration, vaccines, antibacterials, biomolecule detection, imaging probes, and theranostics. Though diverse, these nanosystems can be classified according to foundational inorganic/organic components, accessory moieties, and architecture of hybridization. Within this Review, we begin by providing a historical context for the development of biomedical hybrid nanosystems before describing the properties, synthesis, and characterization of their component building blocks. Afterward, we introduce the architectures of hybridization and highlight recent biomedical nanosystem developments by area of application, emphasizing hybrids of distinctive utility and innovation. Finally, we draw attention to ongoing clinical trials before recapping our discussion of hybrid nanosystems and providing a perspective on the future of the field.

Mesoporous silica nanoparticles (MSNs) offer many advantageous properties for applications in the field of nanobiotechnology. Loading of small molecules into MSNs is straightforward and widely applied, but with the upswing of both research and commercial interest in biological drugs in recent years, also biomacromolecules have been loaded into MSNs for delivery purposes. MSNs possess many critical properties making them a promising and versatile carrier for biomacromolecular delivery. In this chapter, we review the effects of the various structural parameters of MSNs on the effective loading of biomacromolecular therapeutics, with focus on maintaining stability and drug delivery performance. We also emphasize recent studies involving the use of MSNs in the delivery of biomacromolecular drugs, especially for cancer treatment.

Infectious or immune diseases have caused serious threat to human health due to their complexity and specificity, and emerging drug delivery systems (DDSs) have evolved into the most promising therapeutic strategy for drug-targeted therapy. Various mesoporous biomaterials are exploited and applied as efficient nanocarriers to loading drugs by virtue of their large surface area, high porosity, and prominent biocompatibility. Nanosized mesoporous nanocarriers show great potential in biomedical research, and it has become the research hotspot in the interdisciplinary field. Herein, recent progress and assembly mechanisms on mesoporous inorganic biomaterials (e.g., silica, carbon, metal oxide) are summarized systematically, and typical functionalization methods (i.e., hybridization, polymerization, and doping) for nanocarriers are also discussed in depth. Particularly, structure-activity relationship and the effect of physicochemical parameters of mesoporous biomaterials, including morphologies (e.g., hollow, core-shell), pore textures (e.g., pore size, pore volume), and surface features (e.g., roughness and hydrophilic/hydrophobic) in DDS application are overviewed and elucidated in detail. As one of the important development directions, advanced stimuli-responsive DDSs (e.g., pH, temperature, redox, ultrasound, light, magnetic field) are highlighted. Finally, the prospect of mesoporous biomaterials in disease therapeutics is stated, and it will open a new spring for the development of mesoporous nanocarriers.

Simultaneous drug and gene delivery to cancer cells has been introduced to provide advantages of the synergistic effects of gene to sensitize the cancer cells to chemotherapeutic agent. In the current study, nucleolin-targeted co-delivery system, based on PEGylated rod-shaped mesoporous silica NPs was developed as a biocompatible nanocarrier for simultaneous delivery of camptothecin and survivin shRNA-expressing plasmid (iSur-DNA) to colon adenocarcinoma. The structural characterization including hydrodynamic radius and morphological characteristics of the prepared system demonstrated the mesoporous rod-shaped structure of the prepared system with 100-150 nm diameter. Camptothecin was loaded into the rod-shaped MSN NPs with encapsulation efficiency of 32%. At the next stage, the prepared camptothecin-loaded system was PEGylated and then iSur-DNA was condensed with C/P ratio of 6 to form PEG@MSNR-CPT/Sur. Then, the prepared camptothecin-iSur-DNA loaded PEGylated rod-shaped mesoporous silica NPs were tagged with AS1411 DNA aptamer (Apt-PEG@MSNR-CPT/Sur) in order to provide selective therapy against colorectal adenocarcinoma. The obtained results showed that the prepared platform controlled the release of anticancer drug, camptothecin. The experimental results indicated potent synergistic effect of iSur-pDNA and CPT in in vitro cytotoxicity, apoptosis induction and in vivo antitumor effect. In addition, tagging the system with AS1411 DNA aptamer facilitated drug uptake into nucleolin positive colorectal cancer cells leading to higher cellular toxicity and apoptosis induction in C26 cells compared to nucleolin-negative CHO cell line. Apt-PEG@MSNR-CPT/Sur system significantly supressed tumor growth rate in C26 tumor bearing mice while improving survival rate and pharmacokinetics of the platform in comparison with PEG@MSNR-CPT and PEG@MSNR-CPT/Sur. It could be concluded that the developed nucelolin targeted nanomedicine for co-delivery of camptothecin and iSur-DNA could serve as a versatile nanotherapeutic system against colorectal cancer.

First-line chemotherapeutic agents lead to remarkable activation treatment in cancers, but the side effects of these drugs also damage healthy cells. In some cases, drug resistance to chemotherapeutic agents is induced in cancer cells. The molecular mechanisms underlying such a side effect have been studied in a range of cancer types, yet little is known about how the adverse effects of chemotherapeutic drugs can be diminished by targeting bromodomain-containing protein 9 (BRD9) in gastric cancers.

We used two gastric cancer cell lines (MGC-803 and AGS) for comparison. We applied molecular and cellular techniques to measure cell survival and mRNA expression, investigated clinical data in the consensus of The Cancer Genome Atlas, and utilized high-throughput sequencing in MGC-803 cells and AGS cells for global gene expression analysis in inhibiting BRD9 conditions.

Our studies showed that cancer cells with BRD9 overexpression, MGC-803 cells, were more sensitive to BRD9 inhibitors (i.e., BI9564 or BI7273) than AGS cells. The mechanism of BRD9 was related to the regulation of calcium voltage-gated channel auxiliary subunit alpha2 delta 4 (CANA2D4), calmodulin-like 6 (CALML6), guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O (GNAO1) and Potassium Inwardly Rectifying Channel Subfamily J, Member 5 (KCNJ5) oncogenes in the oxytocin signaling pathway. BRD9 inhibitors could enhance the sensitivity of gastric cancer MGC-803 cells to adriamycin and cisplatin, so we may reduce the dosage of chemotherapeutic agents in curing gastric cancers with BRD9 over expression by combining BI9564 or BI7273 with adriamycin or cisplatin.

Our study elucidated the feasibility and effectiveness of inhibiting BRD9 to reduce the adverse effects of first-line chemotherapeutic agents in treating gastric cancer with BRD9 overexpression. This study provides a scientific theoretical basis for a chemotherapy regimen in gastric cancer with BRD9 overexpression.