Phytochemicals, naturally occurring compounds in plants, possess a wide range of therapeutic properties, including antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. However, their clinical application is often hindered by poor water solubility, low bioavailability, rapid metabolism, and instability under physiological conditions. Polymer lipid hybrid nanoparticles (PLHNPs) have emerged as a novel delivery system that combines the advantages of both polymeric and lipid-based nanoparticles to overcome these challenges. This review explores the potential of PLHNPs to enhance the delivery and efficacy of phytochemicals for biomedical applications. We discuss the obstacles in the conventional delivery of phytochemicals, the fundamental architecture of PLHNPs, and the types of PLHNPs, highlighting their ability to improve encapsulation efficiency, stability, and controlled release of the encapsulated phytochemicals. In addition, the surface modification strategies to improve overall therapeutic efficacy by site-specific delivery of encapsulated phytochemicals are also discussed. Furthermore, we extensively discuss the preclinical studies on phytochemical encapsulated PLHNPs for the management of different diseases. Additionally, we explore the challenges ahead and prospects of PLHNPs regarding their widespread use in clinical settings. Overall, PLHNPs hold strong potential for the effective delivery of phytochemicals for biomedical applications. As per the findings from pre-clinical studies, this may offer a promising strategy for managing various diseases.

The death rate from breast cancer (BC) has dropped due to early detection and sophisticated therapeutic options, yet drug resistance and relapse remain barriers to effective, systematic treatment. Multiple mechanisms underlying miRNAs appear crucial in practically every aspect of cancer progression, including carcinogenesis, metastasis, and drug resistance, as evidenced by the elucidation of drug resistance. Non-coding RNAs called microRNAs (miRNAs) attach to complementary messenger RNAs and degrade them to inhibit the expression and translation to proteins. Evidence suggests that miRNAs play a vital role in developing numerous diseases, including cancer. They affect genes critical for cellular differentiation, proliferation, apoptosis, and metabolism. Recently studies have demonstrated that miRNAs serve as valuable biomarkers for BC. The contrast in the expression of miRNAs in normal tissue cells and tumors suggest that miRNAs are involved in breast cancer. The important aspect behind cancer etiology is the deregulation of miRNAs that can specifically influence cellular physiology. The main objective of this review is to emphasize the role and therapeutic capacity of tumor suppressor miRNAs in BC and the advancement in the delivery system that can deliver miRNAs specifically to cancerous cells. Various approaches are used to deliver these miRNAs to the cancer cells with the help of carrier molecules, like nanoparticles, poly D, L-lactic-co-glycolic acid (PLGA) particles, PEI polymers, modified extracellular vesicles, dendrimers, and liposomes. Additionally, we discuss advanced strategies of TS miRNA delivery techniques such as viral delivery, self-assembled RNA-triple-helix hydrogel drug delivery systems, and hyaluronic acid/protamine sulfate inter-polyelectrolyte complexes. Subsequently, we discuss challenges and prospects on TS miRNA therapeutic delivery in BC management so that miRNAs will become a routine technique in developing individualized patient profiles.

This study investigates the anti-cancer potential of recently discovered indole alkaloids from Nauclea Officinalis against third and fourth-generation EGFR mutations using computational tools. Through ADMET profiling, druglikeness prediction, docking, and simulations, we assessed their pharmacokinetics, binding interactions, and stability. Promising druglikeness and binding affinity were observed, particularly for (±)-19-O-butylangustoline, which demonstrated stronger binding against both EGFR mutants. MD simulations confirmed stable interactions, with (±)-19-O-butylangustoline exhibiting the highest stability. These findings highlight these indole alkaloids as potential anti-cancer agents, with (±)-19-O-butylangustoline warranting further optimisation for therapeutic development. This study informs their potential through insights into molecular properties and binding energetics.

Objective: Design, synthesis, characterization, and in silico studies of novel nitrobenzene thiazolyl hydrazones (VIa–VIh) and inhibitory action against the EGFR. Methods: All synthesized compounds were evaluated for their anticancer activity against selected cancer cell lines in vitro utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and EGFR enzymatic assay. Target molecule features were investigated through a computational study that included drug-likeness, ADMET profiling, and molecular docking. Results and Discussion: The compounds (IVb), (IVe), and (IVh) showed prominent anticancer activity with an IC₅₀ value of 15.45, 18.23, 10.69 μM, and 12.75, 16.05, 11.95 μM against chosen cancer cell lines A549, and MCF-7 respectively. Additionally, in vitro EGFR enzymatic activity provided insight into the process of anticancer action of the majority of the active molecules. According to a molecular docking study, every molecule binds to EGFR (PDB ID: 5D41) with high affinities. Conclusions: Among all, derivatives (IVb), (IVe), and (IVh) showed moderate inhibition compared to different tested derivatives. Thus, the present study of all novel nitrobenzene thiazolyl hydrazones could be further optimized to develop new EGFR inhibitors.