Background/Objectives: [6]-Gingerol ([6]-G), a bioactive compound derived from Zingiber officinale (ginger), exhibits strong anticancer potential but is hindered by poor aqueous solubility and low bioavailability. This study aimed to develop and evaluate PEGylated liposomal [6]-G (6-G-Lip) to enhance its stability, bioavailability, and chemopreventive efficacy in benzo[a]pyrene (BaP)-induced lung carcinogenesis. Methods: 6-G-Lip was synthesized using a modified thin-film hydration technique and characterized for size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE%), and release kinetics. The chemopreventive effects were assessed in BaP-induced lung cancer in Swiss albino mice, with prophylactic 6-G-Lip administration from two weeks before BaP exposure through 21 weeks. Cancer biomarkers, antioxidant enzyme activity, reactive oxygen species (ROS) generation, induction of apoptosis, and histopathological alterations were analyzed. Results: 6-G-Lip exhibited a particle size of 129.7 nm, a polydispersity index (PDI) of 0.16, a zeta potential of -18.2 mV, and an encapsulation efficiency (EE%) of 91%, ensuring stability and effective drug loading. The formulation exhibited a controlled release profile, with 26.5% and 47.5% of [6]-G released in PBS and serum, respectively, at 72 h. 6-G-Lip significantly lowered cancer biomarkers, restored antioxidant defenses (SOD: 5.60 U/min/mg protein; CAT: 166.66 μm H2O2/min/mg protein), reduced lipid peroxidation (MDA: 3.3 nm/min/mg protein), and induced apoptosis (42.2%), highlighting its chemopreventive efficacy. Conclusions: This study is the first to prepare, characterize, and evaluate PEGylated [6]-G-Lip for the chemoprevention of lung cancer. It modulates oxidative stress, restores biochemical homeostasis, and selectively induces apoptosis. These findings support 6-G-Lip as a promising nanotherapeutic strategy for cancer prevention.

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the development of effective preventive strategies. Fenugreek (Trigonella foenum-graecum) possesses well-documented pharmacological properties; however, its chemopreventive potential in colorectal cancer (CRC) remains unexplored. This study evaluates the efficacy of methanolic fenugreek seed extract (FSE) in an azoxymethane (AOM)-induced murine colorectal cancer (CRC) model, focusing on the modulation of oxidative stress, regulation of biomarkers, induction of apoptosis, and maintenance of epithelial integrity. Methods: FSE was extracted using cold maceration (yield: 24%) and analyzed by gas chromatography-mass spectrometry (GC-MS), identifying 13 bioactive compounds, including benzene, 1,3-dimethyl-; 1,3-cyclopentadiene, 5-(1-methylethylidene)-; o-Xylene; benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-; and benzene, 1,2,3-trimethyl-. All 13 compounds identified were matched with the NIST library with high confidence. Molecular docking was used to assess the interactions of FSE bioactives with E-cadherin-β-catenin complexes. Swiss albino mice received an FSE pre-treatment before AOM induction and continued this treatment three times weekly for 21 weeks. Key assessments included survival analysis, body weight changes, serum biomarker levels (GGT, 5'-NT, LDH), antioxidant enzyme activities (SOD, CAT, GPx1, MDA), reactive oxygen species (ROS) quantification, apoptosis detection via flow cytometry, and immunofluorescence-based evaluation of E-cadherin dynamics. Results: FSE improved survival rates, mitigated AOM-induced weight loss, and dose-dependently reduced serum biomarker levels. Antioxidant enzyme activity was restored, while MDA levels declined. A dose-dependent increase in ROS facilitated apoptosis, as confirmed by flow cytometry (16.7% in the low-dose FSE group and 34.5% in the high-dose FSE group). Immunofluorescence studies revealed that FSE-mediated restoration of E-cadherin localization counteracted AOM-induced epithelial disruptions. Conclusions: FSE exhibits potent chemopreventive potential against CRC by modulating oxidative stress, regulating key biomarkers, inducing apoptosis, and restoring epithelial integrity. These findings support further investigations into its clinical relevance for CRC prevention.

Since its first written description around 3000 BC until the present day, cancer has stood as a leading global cause of death, claiming the lives of 1 in 6 individuals. Due to its widespread impact and lethality, it remains one of the most explored yet most challenging disease for the global scientific community. Throughout history, various plant extracts have been used in treating numerous diseases, including cancer. These natural extracts are regaining attention due to their therapeutic benefits and lesser side effects. Thymoquinone, chemically 2-isopropyl-5-methylbenzo-1,4-quinone, constitutes the primary bioactive component of the plant Nigella sativa. Extensive research across in vivo, in vitro models, and clinical trials has revealed Thymoquinone's noteworthy therapeutic potential against cancer. Thymoquinone has shown promising anti-cancer activity in various cancers including breast cancer, lung cancer, prostate cancer, colorectal cancer, cervical cancer, pancreatic cancer, gastric cancer and blood cancers. However, there are challenges such as limited clinical trials, low bioavailability, and the need for more research to understand its long-term safety and effectiveness. This article provides a comprehensive and thorough review of thymoquinone, covering its effectiveness across various malignancies, the molecular signalling pathways it influences, and its role in triggering apoptosis and inhibiting inflammation, angiogenesis, and metastasis. Additionally, the review includes a thorough examination of thymoquinone's pharmacokinetics and safety, making it the first of its kind in its comprehensiveness.

Lung cancer is the leading cause of fatalities related to cancer globally. There are numerous ways to treat lung cancer, including surgery, chemotherapy, and radiation. Since these treatments have not yet shown satisfactory results, more research into the underlying mechanisms and different approaches to therapy and prevention are needed. Animal models are essential to the study of lung cancer because they offer priceless information about the etiology, course, and possible treatments for the illness. The therapeutic application of phytochemicals and medicinal plants to treat cancer-related compounds has gained attention subsequently. In addition to discussing the molecular carcinogenic and antitumor effects of the herbal treatment Ocimum sanctum (OS) in connection to lung cancer, this review will address the current awareness regarding lung cancer in animal models. The multitude of animal models used in lung cancer research-such as genetically modified mice, carcinogen-induced models, and xenograft induction-provides a solid foundation for understanding the illness. By easing the examination of the environmental and genetic factors involved and enhancing the analysis of possibilities for treatment, these models eventually assist in the further development of lung cancer therapy. Additionally, using the herb plant OS is essential for both treating and preventing lung cancer. Standardizing dosages and enforcing laws on the use of herbal medications require more in-depth investigation.

Background/Objectives: Colorectal cancer (CRC) remains a major global health burden, necessitating innovative preventive approaches. Artemisia annua (A. annua), known for its extensive pharmacological properties, has shown potential in cancer therapy. This study investigates the chemopreventive efficacy of methanolic extract of A. annua (MEA) in an azoxymethane (AOM)-induced murine model of CRC, with a focus on its antioxidant, biomarker modulation, and pro-apoptotic activities. Methods: MEA was obtained via cold solvent extraction, yielding 39%, and demonstrated potent in vitro cytotoxicity against HCT116 and RKO colon cancer cell lines, with IC50 values of 20 µg/mL and 15 µg/mL, respectively. Swiss albino mice were treated with MEA beginning two weeks before AOM induction, with treatment continuing for 21 weeks. Survival was monitored for 40 weeks. Key outcomes included serum biomarker levels (ADA, GGT, CD73, LDH), antioxidant enzyme activities (SOD, CAT, GPx1, MDA), reactive oxygen species (ROS) modulation, apoptosis induction, and histopathological evaluation. Results: MEA significantly improved survival rates, reduced AOM-induced weight loss, and modulated cancer biomarkers, with marked reductions in ADA, GGT, CD73, and LDH levels. Antioxidant defenses were restored, as evidenced by increased SOD, CAT, and GPx1 activities and decreased MDA levels. ROS levels were significantly reduced, and apoptosis in colonic cells was effectively induced. Histopathological analysis revealed substantial mitigation of CRC-associated morphological abnormalities. Conclusions: MEA exhibits robust chemopreventive properties, demonstrating its potential to reduce oxidative stress, modulate key biomarkers, and induce apoptosis in CRC. These findings position MEA as a promising natural candidate for CRC prevention and therapy, warranting further exploration for clinical application.

Lung inflammation involves the activation of immune cells and inflammatory mediators in response to injury and infection. When inflammation persists, fibroblasts, which are resident lung cells, become activated, leading to pulmonary fibrosis (PF), abnormal wound healing, and long-term damage to the alveolar epithelium. This persistent inflammation and fibrosis can also elevate the risk of lung cancer, emphasizing the need for innovative treatments. Current therapies, such as inhaled corticosteroids (ICS) and chemotherapy, have significant limitations. Although conventional nanoparticles (NPs) provide a promising avenue for treating lung disorders, they have limited selectivity and stability. Polyethylene glycol (PEG) grafting can prevent NP aggregation and phagocytosis, thus prolonging their circulation time. When combined with targeting ligands, PEGylated NPs can deliver drugs precisely to specific cells or tissues. Moreover, pH-sensitive NPs offer the advantage of selective drug delivery to inflammatory or tumor-acidic environments, reducing side effects. These NPs can change their size, shape, or surface charge in response to pH variations, improving drug delivery efficiency. This review examines the techniques of PEGylation, the polymers used in pH-sensitive NPs, and their therapeutic applications for lung inflammation, fibrosis, and cancer. By harnessing innovative NP technologies, researchers can develop effective therapies for respiratory conditions, addressing unmet medical needs and enhancing patient outcomes.

In this study, we have investigated the chemopreventive role of 6-shogaol (6-SGL) on benzopyrene (BaP) exposed lung carcinogenesis by modulating PRDX1-associated oxidative stress, inflammation, and proliferation in Swiss albino mouse models. Mice were exposed to BaP (50 mg/kg b.wt) orally twice a week for four consecutive weeks and maintained for 16 weeks, respectively. 6-SGL (30 mg/kg b.wt) were orally administered to mouse 1 h before BaP exposure for 16 weeks. After the experiment's termination, 6-SGL (30 mg/kg b.wt) prevented the loss in body weight, increased lung weight, and the total number of tumors in the mice. Moreover, we observed that 6-SGL treatment reverted the activity of BaP-induced lipid peroxidation and antioxidants in mice. Also, 6-SGL impeded the phosphorylation of MAPK family proteins such as Erk1, p38, and Jnk1 in BaP-exposed mice. PRDX1 is an essential antioxidant protein that scavenges toxic radicals and enhances several antioxidant proteins. Overexpression of PRDX1 substantially inhibits MAPKs, proliferation, and inflammation signaling axis. Hence, PRDX1 is thought to be a novel targeting protein for preventing BaP-induced lung cancer. In this study, we have obtained the 6-SGL treatment in a mouse model that reverted BaP-induced depletion of PRDX1 expression. Moreover, pretreatment of 6-SGL (30 mg/kg b.wt) significantly inhibited enhanced proinflammatory cytokines (TNF-α, IL-6, IL-β1, IL-10) and proliferative markers (Cyclin-D1, Cyclin-D2, and PCNA) in BaP-exposed mice. The histopathological studies also confirmed that 6-SGL effectively protected the cells with less damage. Thus, the study demonstrated that 6-SGL could be a potential phytochemical and act as a chemopreventive agent in BaP-induced lung cancer by enhancing PRDX1 expression.

Targeted gemcitabine (GEB) loaded 5-N-acetyl-neuraminic acid (Neu5Ac) assembled chitosan nanoparticles (CA-NPs) were formulated by ionotropic gelation process and evaluated for physicochemical and morphological characterization, in vitro and in vivo studies in A-549 cells and lung cancer mice model, respectively. The mean diameter of GEB-CA-Neu5Ac-NPs determined by dynamic light scattering was 161.16 ± 7.70 nm with a polydispersity index (PDI) value of 0.303 ± 0.011 and its zeta potential and entrapment efficiency (%EE) were 40.3 ± 3.45 mv and 66.11 ± 1.94%, respectively. The in vitro cellular uptake studies showed that glycan receptor-targeted nanoparticles deliver significantly more amount (p < 0.001) of GEB into the A-549 lung cancerous cells than non-targeted nanoparticles. The cytotoxicity study using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay clearly demonstrated that GEB-CA-Neu5Ac-NPs have lower IC50 value (6.39 ± 3.78 µg/ml) than others groups that showed that the greater lung cancerous cells inhibition potential of targeted nanoparticles. The in vivo biodistribution of the GEB-loaded 5-N-acetyl-neuraminic acid conjugated chitosan nanoparticles was revealed that targeted nanoparticles showed higher accumulation and retention for an extended period of time due to the active targeting ability of Neu5Ac to glycan receptors. Histopathological examination showed significant recovery in the physiological architecture upon administration of targeted nanoparticles. The glycan receptor-targeted nanoparticles treated groups showed a significant decline in the number of metastatic lung epithelial cells, as compared to the untreated positive control group (p < 0.001) confirming higher anticancer efficacy of the GEB-CA-Neu5Ac-NPs.

Lung cancer (LC), related with the enhanced expression of epidermal growth factor receptor (EGFR) and sialic acid binding receptors (glycan) brought about the development of EGFR and glycan receptor specific anticancer therapeutics. The current study assessed the formulation, physiochemical characterization, in vitro and in vivo effects of sialic acid (SA) and cetuximab (Cxmab) decorated chitosan nanoparticles (CSN-NPs) loaded with gemcitabine (GMC) targeted to glycan and EGFR over-expressing non-small-cell lung-cancer (NSCLC) A-549 cells. Chitosan (CSN) was conjugated with sialic acid via EDC/NHS chemistry followed by gemcitabine loaded sialic acid conjugated chitosan nanoparticles (GMC-CSN-SA-NPs) were prepared by ionic gelation method decorated with Cxmab by electrostatic interaction. In vitro cytotoxicity of NPs quantified using cell based MTT, DAPI and Annexing-V/PI apoptosis assays showed superior antiproliferative activity of targeted nanoformulations (GMC-CSN-SA-Cxmab-NPs ≫ GMC-CSN-SA-NPs, GMC-CSN-Cxmab-NPs) over non-targeted nanoformulation (GMC-CSN-NPs) against A-549 cells. In vivopharmacokinetic study showed superior bioavailability and in vivo therapeutic efficacy investigation exhibited strongest anticancer activity of glycan and EGFR targeted NPs (GMC-CSN-SA-Cxmab-NPs). GMC-CSN-SA-Cxmab-NPs demonstrated enhanced cellular internalization and better therapeutic potential, by specifically targeting glycan and EGFR on NSCLC A-549 cells and B[a]P induced lung cancer mice model, hence it might be a good substitute for non-targeted, conventional chemotherapy.

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators.

Although various treatments are currently being developed, lung cancer still has a very high mortality rate. Moreover, while various strategies for the diagnosis and treatment of lung cancer are being used in clinical settings, in many cases, lung cancer does not respond to treatment and presents reducing survival rates. Cancer nanotechnology, also known as nanotechnology in cancer, is a relatively new topic of study that brings together scientists from a variety of fields, including chemistry, biology, engineering, and medicine. The use of lipid-based nanocarriers to aid drug distribution has already had a significant impact in several scientific fields. Lipid-based nanocarriers have been demonstrated to help stabilize therapeutic compounds, overcome barriers to cellular and tissue absorption, and improve in vivo drug delivery to specific target areas. For this reason, lipid-based nanocarriers are being actively researched and used for lung cancer treatment and vaccine development. This review discusses the improvements in drug delivery achieved with lipid-based nanocarriers, the obstacles that still exist with in vivo applications, and the current clinical and experimental applications of lipid-based nanocarriers in lung cancer treatment and management.

Tendinopathies represent about 45% of musculoskeletal lesions and they are a big burden in clinics characterized by activity-related pain, focal tendon tenderness and intra-tendinous imaging changes. Many approaches have been proposed for tendinopathies' management (e.g., nonsteroidal anti-inflammatory drugs, corticosteroids, eccentric exercises, laser therapy), unfortunately with very little support of efficacy or serious side effects, thus making the identification of new treatments fundamental. The aim of the study was to test the protective and pain reliever effect of thymoquinone (TQ)-loaded formulations in a rat model of tendinopathy induced by carrageenan intra-tendon injection (20 µL of carrageenan 0.8% on day 1). Conventional (LP-TQ) and hyaluronic acid (HA)-coated TQ liposomes (HA-LP-TQ) were characterized and subjected to in vitro release and stability studies at 4 °C. Then, TQ and liposomes were peri-tendon injected (20 µL) on days 1, 3, 5, 7 and 10 to evaluate their antinociceptive profile using mechanical noxious and non-noxious stimuli (paw pressure and von Frey tests), spontaneous pain (incapacitance test) and motor alterations (Rota rod test). Liposomes containing 2 mg/mL of TQ and covered with HA (HA-LP-TQ2) reduced the development of spontaneous nociception and hypersensitivity for a long-lasting effect more than the other formulations. The anti-hypersensitivity effect matched with the histopathological evaluation. In conclusion, the use of TQ encapsulated in HA-LP liposomes is suggested as a new treatment for tendinopathies.

The temperature sensitive liposomal formulations are a promising tool to improve the therapeutic index of the drugs with minimal toxicity. The aim of this study was to investigate the potential of concomitant delivery of cisplatin (Cis) and doxorubicin (Dox) containing thermosensitive liposomes (TSLs) with mild hyperthermia against cancer in vitro and in vivo. The polyethylene glycol coated DPPC/DSPC, thermosensitive and DSPC, non-thermosensitive liposomes incorporating Cis and Dox were prepared and characterized. A conventional Differential Scanning Calorimetry (DSC) technique and Fourier Transform Infrared Spectroscopy (FT-IR) were applied to study drug-phospholipid interaction and compatibility. The chemotherapeutic efficacy of these formulations was evaluated in benzo[a]pyrene (BaP) induced fibrosarcoma under hyperthermic condition. The size diameter of prepared thermosensitive liposomes was measured to be 120 ± 10 nm. The DSC data exhibited the changes in the curves of DSPC + Dox and DSPC + Cis while comparing the pure DSPC and drugs. However, the FITR showed same spectrum of phospholipids and drugs individually and in the mixture as well. The data showed higher efficacy of Cis-Dox-TSL as 84% inhibition in tumor growth was recorded in this group of animals in hyperthermic condition. The Kaplan-Meir curve revealed, 100% and 80% survival of the animals in the groups treated with Cis-Dox-TSL under hyperthermia and Cis-Dox-NTSL without hyperthermia, respectively. However, Cis-TSL as well as Dox-TSL exhibited 50% survival, while only 20% survival was recorded in the groups of animals treated with Dox-NTSL and Cis-NTSL. The flow cytometry analysis revealed that Cis-Dox-NTSL augments the induction of apoptosis in the tumor cells which was recorded as 18%. As expected, Cis-Dox-TSL showed great potential as 39% of cells were measured as apoptotic cells, significantly very high in comparison to Cis-Dox-NTSL, Dox-TSL and Cis-TSL as well. The apoptotic analysis of the cells by flow cytometry clearly indicated the effect of hyperthermia during the treatment while Cis-Dox-TSL formulation was administered. Finally, the immunohistochemical analysis of the tumor tissues by confocal microscopy exhibited several fold increases in the expression of pAkt in the animals treated with vehicles in Sham-NTSL as well as Sham-TSL. However, Cis-Dox-TSL showed great reduction in the expression of Akt, as it declined by 11-fold. The results of the present study directed the role of concomitant delivery doxorubicin and cisplatin containing thermosensitive liposomes under hyperthermic conditions for the development of a novel therapeutic strategy for the treatment of cancer.

Artemisia annua (A. annua) has been used as a medicinal plant in the treatment of several infectious and non-infectious diseases in the forms of tea and press juice since ancient times. The aim of this study was to evaluate the aqueous extract of A. annua (AAE) as an antimicrobial agent in vitro and to evaluate its chemopreventive efficacy in vivo in a small-cell lung cancer (SCLC) animal model. The dried powder of AAE was prepared using the Soxhlet extraction system from the leaves of Artemisia annua. The in vitro activity of AAE was determined against Candida albicans (C. albicans), Enterococcus faecalis (E. faecalis), Klebsiella pneumoniae (K. pneumoniae), and methicillin-resistant Staphylococcus aureus (MRSA) using the agar well diffusion method and propidium iodide (PI)-stained microbial death under a confocal microscope. The pretreatment of mice with AAE was initiated two weeks before the first dose of benzo[a]pyrene and continued for 21 weeks. The chemopreventive potential of the extract was evaluated by flow cytometry and biochemical and histopathological analyses of the tissues and serum accordingly, after sacrificing the mice. The data revealed the antimicrobial potential of AAE against all the species investigated, as it showed growth-inhibitory activity by MIC, as well as confocal microscopy. The pretreatment of AAE exhibited significant protection in carcinogen-modulated, average body weight (ABW), and relative organ weight (ROW) cancer biomarkers in the serum and antioxidants in the lungs. The hematoxylin and eosin (H&E) staining of the tissues revealed that AAE prevented malignancy in the lungs. AAE also induced apoptosis and decreased intracellular reactive oxygen species (ROS) in the lung cells analyzed by flow cytometry. The current findings demonstrated the use of AAE as an alternative medicine in the treatment of infectious disease and the chemoprevention of lung cancer. To our knowledge, this is the first study that summarizes the chemopreventive potential of AAE in a lung cancer model in vivo. However, further investigations are suggested to understand the role of AAE to potentiate the therapeutic index of the commercially available drugs that show multiple drug resistance against microbial growth and high toxicity during cancer chemotherapy.