Parasuraman Pavadai

Globally, breast cancer is the most common cause of cancer‐related deaths in women. Despite considerable scientific advancements in drug design and discovery, the mortality rate has increased. However, finding precision breast cancer therapy and high‐efficiency anticancer drug delivery is still a considerable difficulty. A major challenge in cancer therapy is the lack of a highly selective drug‐delivery system that targets malignant cells without damaging healthy cells, thereby minimizing off‐target effects. Recently, novel drug delivery platforms based on plant‐derived polymeric materials have been rapidly developed, improving pharmacokinetic and therapeutic benefits for breast cancer treatment. Plant‐derived polymers can enable selective targeting, prolonged circulation, enhance drug delivery, and regulate cargo release through various methods with little or no toxicity. Polysaccharides, proteins, and gums are plant‐derived polymers that can self‐assemble and encapsulate both hydrophobic and hydrophilic chemotherapeutic agents. They can also protect drugs from harsh environmental conditions, such as ultraviolet light, enzymes, temperature fluctuations, gastric acid, and pH changes. The biomimetic and bio‐inspired, technology‐enabled, plant‐derived, polymer‐based nanocarriers hold promise for successful drug delivery and can help overcome these challenges. Furthermore, the surface modification of plant‐derived polymer‐based nanoparticles (NPs) enables them to respond to stimuli and deliver drugs efficiently. As a result, plant‐derived polymers are ideal nanocarriers for the targeted delivery of chemotherapies to treat breast cancer. This review summarizes recent developments in plant‐derived polymer‐based drug delivery systems for breast cancer therapy and discusses their future potential for designing safer, more effective anticancer treatments.

Breast cancer is a prevalent and aggressive tumor affecting women, known for its molecular diversity and treatment resistance. This study investigates the anticancer potential of Icariin (ICA), a flavonol glycoside derived from Herba epimedii, against breast cancer using network pharmacology and molecular simulation. Using the SwissTargetPrediction database and GeneCards, the researchers identified 98 common targets shared by ICA and breast cancer. Gene ontology (GO) and KEGG enrichment analyses highlighted the targets' roles in the regulation of apoptosis, inflammatory signaling, receptor tyrosine kinase activity, chemokine signaling, sphingolipid metabolism, and VEGF pathways. Molecular docking revealed ICA's strong binding affinity for key oncogenic proteins, with binding energies ranging from −12 to −7.5 kcal/mol, particularly to SER783, THR862, ASP863, LYS753, and ARG849. Molecular dynamics (MD) simulations demonstrated the structural stability of the ICA‐HER2 complex, which maintained strong hydrogen bonds and exhibited minimal conformational changes over a 1000 ns trajectory, with average RMSD values of 1.7 Å for the protein and 1.0 Å for the protein‐ligand complex. Furthermore, ICA exhibited favorable pharmacokinetic properties, including moderate solubility and negligible inhibition of cytochrome P450. These findings support the hypothesis that ICA may serve as a valuable natural compound for treating HER2‐driven breast cancer; it requires further experimental validation.

The incidence of chronic kidney disease (CKD), which is believed to be between 10% and 14% worldwide, is a growing public health concern. The study’s main objective was to investigate the nephroprotective and nephrocurative properties of the folk plant Orthosiphon stamineus using molecular docking and dynamics analyses to assess its potential for treating CKD. Graph-theoretical network analysis identified the transcription factor Krüppel-like factor 4 (KLF4) as a significant therapeutic target for CKD. Eighty-four phytochemicals were identified from public repositories and docked against the KLF4 protein, and their binding affinities were compared with those of the standard CKD drug Furosemide. Based on the docking results Neoschaftoside (−6.9 kcal/mol), Hederagenin (−6.8 kcal/mol), Stigmasterol (−6.8 kcal/mol), Orthosiphol D (−6.8 kcal/mol), Beta-Sitosterol (−6.6 kcal/mol), Eupatorin (−6.4 kcal/mol), Sinensitin (−6.4 kcal/mol) having a higher binding affinity than the standard drug Furosemide (−6.2 kcal/mol), were chosen for further studies among the 84 compounds from Orthosiphon stamineus. Furthermore, the Eupatorin and Sinensetin molecules exhibited substantial drug-likeness and Absorption, Distribution, Metabolism, and Excretion (ADME) properties, along with reduced toxicity profiles. Neoschaftoside, Eupatorin, and Sinensetin appear to establish robust and specific interactions with KLF4 that are comparable to, or even better than, those of the common medication Furosemide, according to MD simulation results. Hence, the Eupatorin and Sinensetin molecules, with further in vitro and in vivo analyses, can be used as potent and safe drug candidates for managing CKD.

Checkpoint 1 kinase (Chk1) regulates the cell cycle and facilitates DNA repair processes, which are essential for maintaining genomic integrity. In breast cancer, Chk1 is frequently overexpressed, enabling tumor cells to endure DNA damage. By blocking Chk1, a crucial regulator of the development and spread of malignancies, the current study investigates the potential of natural products to identify different treatment approaches for breast cancer. Based on the molecular docking, absorption, distribution, metabolism, excretion, and toxicity profiling and molecular dynamics simulations, hesperidin (NP621) interacted with important Chk1 residues, demonstrated good stability over 800 ns, and had a favorable binding energy of -9.6 kcal/mol. Liposomal encapsulation was employed to overcome hesperidin's low solubility and poor bioavailability, thereby enhancing its stability and therapeutic potential in cancer treatment. The liposomal formulations were characterized by Fourier transform infrared, X-ray diffraction, and transmission electron microscopy (FTIR, XRD, particle size analysis, and TEM), confirming successful liposomal binding. Hesperidin encapsulated liposomes (HSP-LLPs) displayed remarkable cytotoxicity against the MCF-7 breast cancer cells (IC₅₀ of 13.52 μg/mL) and significantly inhibited angiogenesis in the chorioallantoic membrane assay. HSP-LLPs reduced tumor burden, restored hematological and biochemical parameters, and improved tissue architecture in a 7,12-dimethylbenz[α]anthracene-induced rat model of breast cancer. These findings demonstrate that Chk1-targeted hesperidin liposomes represent a promising translational nanomedicine approach for breast cancer therapy.

Infected wound healing is delayed due to compromised immunity and antimicrobial resistance. Antibiotic resistance is an emerging threat due to the unnecessary use of antibiotics. Current wound dressings that promote chronic wound healing either require additional processes, such as photothermal irradiation, or leave behind large amounts of undesirable residues. Gramicidin D (GCN), a mixture of gramicidin A, B, and C derived from Bacillus brevis, is a linear antimicrobial peptide that has been shown to exhibit wound healing properties in recent studies. In silico molecular docking simulations of GCN were conducted to preliminarily explore its potential interactions with proteins associated with the wound-healing process. The analysis suggested possible binding interactions with MMP3 and MMP7, indicating a hypothetical mechanism that may warrant further experimental validation, rather than establishing a direct role in the observed wound-healing effects. Therefore, in this study, we report a dual-functionality chitosan (CS) hydrogel dressing enriched with GCN and a multifunctional, non-reducing carbohydrate moiety called trehalose (TH) for combating antimicrobial resistance and accelerating infected wound healing. The GCN- and TH-enriched hydrogel matrix was successfully developed using an ionic-crosslinking method and optimised with the Box-Behnken Design (BBD) approach using Design Expert Software. The developed hydrogel formulation demonstrated controlled GCN release, suitable physicochemical properties, and excellent antibacterial and antibiofilm potential. Moreover, the in vitro cell line data on HaCaT cells indicated suitable biocompatibility, non-toxic behaviour and enhanced cell migration. Additionally, an in vivo chronic infectious wound healing study confirmed that the GCN and TH dual-functional hydrogel promotes accelerated healing in rats. This approach represents a potential therapeutic strategy for the rapid healing of chronically infected wounds in a multifunctional manner.

Breast cancer, particularly the Human Epidermal Growth Factor Receptor 2 (HER2)-positive subtype, remains a significant clinical challenge due to its aggressive nature and the frequent development of resistance to targeted therapy. In this study, we created a comprehensive machine-learning (ML)-based drug repurposing framework to identify new HER2 inhibitors among FDA-approved drugs. A carefully curated dataset of 13,944 HER2 bioactivity records from BindingDB was used to build high-accuracy predictive models. This involved optimizing descriptors, reducing dimensionality, and selecting key features. The Random Forest model trained on 75 optimized descriptors demonstrated the best performance (R² = 0.81, RMSE = 0.86, MAE = 0.6483). This allowed us to understand structure-activity relationships and perform reliable virtual screening of 4,099 FDA-approved drugs. Docking studies against HER2 wild-type (7PCD) revealed strong interactions, with scores from -10.5 to -7.5 kcal/mol. For the exon-20 insertion mutant (8U8X), the affinities were even higher (-11.6 to -8.0 kcal/mol), exceeding the reference co-crystal ligand in both cases. FDA0870 (Timolol maleate) consistently ranked as a top dual inhibitor, forming stable hydrogen bonds and hydrophobic contacts with key catalytic residues of both wild-type and mutant HER2. Molecular dynamics simulations supported its stability, with wild-type HER2-FDA0870 complexes showing an average protein RMSD of 3.4 Å and a ligand RMSD of 2.9 Å, whereas mutant complexes had an average protein RMSD of 3.9 Å and a ligand RMSD of 2.1 Å over extended trajectories. Persistent interactions with residues such as ASP863/ASP867, THR862/THR866, and LYS753 were observed. ADMET analysis indicated that the drug had good drug-like properties, moderate permeability, a high unbound fraction, and acceptable safety features, suggesting its potential for further development. This integrated ML, docking, MD, and ADMET approach demonstrates that FDA0870 is a promising repurposed dual inhibitor for HER2-positive and HER2-mutant breast cancer, highlighting the value of computational pipelines in speeding up the search for targeted cancer therapies.