Targeting triple negative breast cancer stem cells using nanocarriers

Abstract Breast cancer is a complex and heterogeneous disease, encompassing various subtypes characterized by distinct molecular features, clinical behaviors, and treatment responses. Categorization of subtypes is based on the presence or absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), leading to subtypes such as luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). TNBC, comprising around 20% of all breast cancers, lacks expression of ER, PR, and HER2 receptors, rendering it unresponsive to targeted therapies and presenting significant challenges in treatment. TNBC is associated with aggressive behavior, high rates of recurrence, and resistance to chemotherapy. Tumor initiation, progression, and treatment resistance in TNBC are attributed to breast cancer stem cells (BCSCs), which possess self-renewal, differentiation, and tumorigenic potential. Surface markers, self-renewal pathways (Notch, Wnt, Hedgehog signaling), apoptotic protein (Bcl-2), angiogenesis inhibition (VEGF inhibitors), and immune modulation (cytokines, immune checkpoint inhibitors) are among the key targets discussed in this review. However, targeting the BCSC subpopulation in TNBC presents challenges, including off-target effects, low solubility, and bioavailability of anti-BCSC agents. Nanoparticle-based therapies offer a promising approach to target various molecular pathways and cellular processes implicated in survival of BSCS in TNBC. In this review, we explore various nanocarrier-based approaches for targeting BCSCs in TNBC, aiming to overcome these challenges and improve treatment outcomes for TNBC patients. These nanoparticle-based therapeutic strategies hold promise for addressing the therapeutic gap in TNBC treatment by delivering targeted therapies to BCSCs while minimizing systemic toxicity and enhancing treatment efficacy. Graphical abstrac

RAGE receptor targeted bioconjuguate lipid nanoparticles of diallyl disulfide for improved apoptotic activity in triple negative breast cancer: in vitro

In the present study, we have demonstrated receptor for advanced glycation endproducts (RAGE) as a target for delivery of drugs specifically to triple negative breast cancer cells. We have prepared solid lipid nanoparticle formulation of cytotoxic agent di-allyl-disulfide (DADS) to overcome its bioavailability issues. Then, we have surface modified DADS-loaded solid lipid nanoparticles (DADS-SLN) with RAGE antibody to achieve site-specific delivery of DADS to TNBC cells. We found a significant cellular internalization of RAGE surface modified DADS-SLN (DADS-RAGE-SLN) when compared to DADS-SLN. The cytotoxic effect of DADS was also significantly improved with DADS-RAGE-SLN by downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as observed by western blot analysis. RAGE-targeted delivery of cytotoxic agents can be, therefore, a promising approach for improving antitumour activity and reducing off-target effects

TARGETING ANGIOGENESIS WITH FLUPHENAZINE-ZINC OXIDE NANOCONJUGATES: A POTENTIAL MECHANISM FOR IMPROVING ANTIPSYCHOTIC EFFICACY

This study aimed to develop a more effective formulation of Fluphenazine (FLP) for the management of psychosis. Antipsychotics are widely used for the treatment of severe mental disorders such as schizophrenia and bipolar disorder. However, their clinical use is limited due to various side effects and low efficacy in a large number of patients. Nanoparticle-based drug delivery systems have shown great potential in improving the pharmacokinetics and pharmacodynamics of various drugs, including antipsychotics. Zinc oxide nanoparticles (ZnO NPs) have emerged as a promising carrier for drug delivery due to their unique physicochemical properties, biocompatibility, and low toxicity. In this study, we reported the preparation and characterization of FLU encapsulated ZnO NPs (FLU-ZnO-NPs) for the management of psychosis. The synthesized FLU-ZnO-NPs were characterized using various techniques, such as X-Ray Diffractometer, Energy Dispersive X-Ray analysis, Transmission Electron Microscopy, and Zetasizer (Malvern). The characterization results showed that the synthesized FLU-ZnO-NPs had improved solubility, enhanced bioavailability, targeted delivery, and reduced toxicity. The development of FLU-ZnO-NPs could provide a more effective and safe treatment option for patients with mental disorders