Farah Rehan

Background and purpose: Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), play crucial roles in embryogenesis, tissue regeneration, and cancer progression. Dys­regulation of EMT/MET pathways in cancer contributes to metastasis and drug resistance. Approach: This review discusses the signalling pathways that are correlated with EMT in cancer and investigates the therapeutic potential of naturally occurring compounds in modulating these processes. The intricate relationship between stromal cells, drug resistance, and EMT is discussed, highlighting the emerging role of MET in stabilizing distant metastasis. Additionally, the impact of p53 on EMT and its implications in cancer metastasis are discussed. The review also provides an overview of therapeutic molecules, both plant- and animal-derived, that regulate EMT, highlighting their potential in cancer treatment. Specifically, plant-based compounds from Atractylodes lancea, Dendrobium officinale, Panax ginseng and Platycodon grandiflorus, as well as animal-derived substances like bee venom and snake venom, are highlighted. Furthermore, marine-based compounds, including caprolactin C, laminaran sulfate, BFP-3, bryostatin 1, sinulariolide, manzamines, halichondrin B, eribulin and biemamides, exhibit significant anti-metastatic effects by targeting EMT-associated pathways. Conclusion: The diverse range of therapeutic molecules discussed in this review provides promising therapeutic avenues for developing targeted strategies against EMT in cancer.

The concept of nanomedicine has evolved significantly in recent decades, leveraging the unique phenomenon known as the enhanced permeability and retention (EPR) effect. This has facilitated major advancements in targeted drug delivery, imaging, and individualized therapy through the integration of nanotechnology principles into medicine. Numerous nanomedicines have been developed and applied for disease treatment, with a particular focus on cancer therapy. Recently, nanomedicine has been utilized in various advanced fields, including diagnosis, vaccines, immunotherapy, gene delivery, and tissue engineering. Multifunctional nanomedicines facilitate concurrent medication delivery, therapeutic monitoring, and imaging, allowing for immediate responses and personalized treatment plans. This review concerns the major advancement of nanomaterials and their potential applications in the biological and medical fields. Along with this, we also mention the various clinical translations of nanomedicine and the major challenges that nanomedicine is currently facing to overcome the clinical translation barrier.

Cancer remains a global health crisis, claiming countless lives throughout the years. Traditional cancer treatments like chemotherapy and radiation often bring about severe side effects, underscoring the pressing need for innovative, more efficient, and less toxic therapies. Nanotechnology has emerged as a promising technology capable of producing environmentally friendly anticancer nanoparticles. Among various nanoparticle types, metal‐based nanoparticles stand out due to their exceptional performance and ease of use in methods of imaging. The widespread accessibility of biological precursors for synthesis based on plants of metal nanoparticles has made large‐scale, eco‐friendly production feasible. This evaluation provides a summary of the green strategy for synthesizing metal‐based nanoparticles and explores their applications. Moreover, this review delves into the potential of phyto‐based metal nanoparticles in combating cancer, shedding light on their probable mechanisms of action. These insights are invaluable for enhancing both biomedical and environmental applications. The study also touches on the numerous potential applications of nanotechnology in the field of medicine. Consequently, this research offers a concise and well‐structured summary of nanotechnology, which should prove beneficial to researchers, engineers, and scientists embarking on future research endeavors.

Poor prognosis, drug resistance, and lower drug loading capacity of the delivery systems lead to therapeutic failures of breast cancers. Herein we functionalized sodium caseinate nanomicelles (NaCNs) with the divalent calcium (Ca2+) and the glucose (Glc) to increase the loading capacity of micelles for higher cellular uptake and cytotoxicity against breast cancer cells. Modification of casein micelles was confirmed through Fourier Transform Infrared Spectra (FTIR). Triple quadrupole liquid chromatography-mass spectrometry method (TQOF-LCMS/MS) was used as a simple, rapid, and sensitive method for protein corona quantification around casein through SwissProt.Mus_musculus database and through de novo sequencing. Un-modified and modified casein micelles were further characterized through Field Emission Scanning Electron Microscope (FESEM), High Resolution-Transmission Electron Microscope (HR-TEM), and Energy Dispersive X-Ray (EDX). Whereas, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-page) was used for protein separation and analysis during micelles formation. Calcium divalent modified sodium caseinate nanomicelles (Ca-NaCNs) and glucose-modified sodium casemate nanomicelles (Glc-NaCNs) were successfully developed and these demonstrated a significantly improved micellar stability. Doxorubicin-loaded modified NaCNs manifested higher drug loading and enhanced cellular uptake by improved drug binding affinity. Modified NaCNs exhibit the potential to be investigated further as a novel delivery system for similar active moieties to maximize their therapeutic effects.

Purpose: Natural materials have been extensively studied for oral drug delivery due to their biodegradability and other unique properties. In the current research, we fabricated sodium caseinate nanomicelles (NaCNs) using casein as a natural polymer to develop a controlled-release oral delivery system that would improve the therapeutic potential of doxorubicin (DOX) and reduce its toxicity. Methods: DOX-loaded NaCNs were synthesized and thoroughly characterized, then subjected to in vivo anti-tumor evaluation and bio-distribution analysis in a 4T1-induced breast cancer model. Results: Our findings indicated that the tumor would shrink by eight-fold in the group orally treated with DOX-NaCNs when compared to free DOX. The tumor accumulated drug 1.27-fold more from the orally administered DOX-NaCNs compared to the intravenously administered DOX-NaCNs, 6.8-fold more compared to free DOX, and 8.34-times more compared to orally administered free DOX. In comparison, the orally administered DOX-NaCNs lead to a significant reduction in tumor size (5.66 ± 4.36 mm³) compared to intravenously administered DOX-NaCNs (10.29 ± 4.86 mm³) on day 17 of the experiment. NaCNs were well tolerated at a single dose of 2000 mg/kg in an acute oral toxicity study. Conclusion: The enhanced anti-tumor effects of oral DOX-NaCNs might be related to the controlled release of DOX from the delivery system when compared to free DOX and the intravenous formulation of DOX-NaCNs. Moreover, NaCNs is recognized as a safe and non-toxic delivery system with excellent bio-distribution profile and high anti-tumor effects that has a potential for oral chemotherapy.

Background: Paclitaxel (PTX) is a widely used anti-cancer drug for treating various types of solid malignant tumors including breast, ovarian and lung cancers. However, PTX has a low therapeutic response and is linked with acquired resistance, as well as a high incidence of adverse events, such as allergic reactions, neurotoxicity and myelosuppression. The situation is compounded when its complex chemical structure contributes towards hydrophobicity, shortening its circulation time in blood, causing off-target effects and limiting its therapeutic activity against cancer cells. Formulating a smart nano-carrier may overcome the solubility and toxicity issues of the drug and enable its more selective delivery to the cancerous cells. Among the nano-carriers, natural polymers are of great importance due to their excellent biodegradability, non-toxicity and good accessibility. The aim of the present research is to develop self-assembled sodium caseinate nanomicelles (NaCNs) with PTX loaded into the hydrophobic core of NaCNs for effective uptake of the drug in cancer cells and its subsequent intracellular release. Methods: The PTX-loaded micelle was characterized with high-performance liquid chromatography (HPLC), Fourier Transform Infrared Spectra (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM), Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-Ray (EDX). Following treatment with PTX-loaded NaCNs, cell viability, cellular uptake and morphological changes were analyzed using MCF-7 and MDA-MB 231 human breast cancer cell lines. Results: We found that PTX-loaded NaCNs efficiently released PTX in an acidic tumor environment, while showing an enhanced cytotoxicity, cellular uptake and in-vivo anti-tumor efficacy in a mouse model of breast cancer when compared to free drug and blank micelles. Additionally, the nanomicelles also presented improved colloidal stability for three months at 4 °C and −20 °C and when placed at a temperature of 37 °C. Conclusions: We conclude that the newly developed NaCNs is a promising carrier of PTX to enhance tumor accumulation of the drug while addressing its toxicity issues as well.