Nanomedicine strategies for overcoming multidrug resistance in breast cancer: recent advances and future perspectives

Nanocarrier strategies to overcome P-glycoprotein-mediated drug resistance in cancer therapy

Overall, nanoparticle-mediated modulation of P-gp represents a promising strategy toward precision oncology, although future success will depend on scalable design, mechanistic standardization, and biomarker-guided clinical implementation.

Advancements in Lipid Nanotechnology for the Treatment of Triple-Negative Breast Cancer: Mechanistic Insights and Future Prospects

The high resistance to therapy, molecular heterogeneity, early metastasis, and quick drug resistance make triple-negative breast cancer (TNBC) difficult and even impossible to treat. The conventional chemotherapy is highly toxic, not specifically targeting the tumor, and has limited efficacy, so more sophisticated delivery mechanisms are required. To overcome these shortcomings, lipid nanotechnology is provided as a controlled, targeted, and multifunctional drug delivery system. This review outlines the recent developments of lipid nanoparticles for TNBC, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, lipidpolymer hybrids, ionizable lipid nanoparticles, and biomimetic vesicles. These systems enable improved tumor targeting and delivery of chemotherapeutics, gene editing agents, and combination therapeutics. Rational design, targeting strategies, modulation of the tumor microenvironment, targeting cancer stem cells, and breaking multidrug resistance are highlighted. Pharmacokinetic, safety, manufacturing, regulatory, and translational issues are discussed, along with pre-clinical and emerging clinical evidence. Lastly, future directions are suggested to help develop modular, precise, and clinically scalable lipid nanoparticle systems for effective management of TNBC.

Cancer Nanomedicine: Advanced Nanocarrier Systems, Targeted Drug Delivery, Theranostics, and Emerging Strategies for Precision Oncology

Cancer remains one of the leading causes of morbidity and mortality worldwide despite substantial advances in diagnosis and treatment. Conventional therapeutic approaches, including chemotherapy, radiotherapy, surgery, and immunotherapy, are often limited by poor tumor selectivity, systemic toxicity, multidrug resistance, and inadequate drug accumulation at the disease site. Nanomedicine has emerged as a transformative strategy in oncology, offering innovative solutions for targeted drug delivery, improved pharmacokinetics, enhanced therapeutic efficacy, and reduced off-target toxicity. Owing to their unique physicochemical properties, nanoparticles can be engineered to overcome biological barriers associated with tumor progression and facilitate precise delivery of therapeutic and diagnostic agents. This review comprehensively discusses the fundamental principles of cancer nanomedicine, including tumor biology, barriers to drug delivery, and critical design considerations for nanocarrier development. Various classes of nanomaterials, including polymeric nanoparticles, lipid-based systems, inorganic nanomaterials, and emerging biomimetic platforms, are examined with respect to their structural characteristics, therapeutic applications, and translational potential. Particular emphasis is placed on tumor-targeting strategies, encompassing passive, active, and microenvironment-responsive approaches, as well as on the development of smart stimuli-responsive nanocarriers capable of controlled, site-specific drug release. Furthermore, recent advances in nanotechnology-enabled chemotherapy, combination therapy, gene and RNA delivery, immuno-nanomedicine, and theranostic platforms are highlighted. The integration of diagnostic imaging and therapeutic functions within multifunctional nanocarriers has enabled real-time monitoring of treatment response and personalized cancer management. In addition, challenges associated with safety, toxicity, large-scale manufacturing, regulatory approval, and clinical translation are critically evaluated. Emerging innovations, including artificial intelligence-driven nanocarrier design, biomimetic nanomedicines, and precision oncology approaches, are also explored as future directions for the field.Overall, cancer nanomedicine has evolved from a simple drug-delivery concept into a multifunctional therapeutic platform integrating targeted therapy, molecular imaging, immunomodulation, gene therapy, and personalized medicine. Continued interdisciplinary collaboration and technological innovation are expected to accelerate the clinical translation of next-generation nanomedicines, ultimately improving treatment outcomes and advancing precision cancer care.

THERAPEUTIC ROLE OF siRNA IN GASTRIC CANCER: GENE SILENCING MECHANISMS AND NANOCARRIER-BASED DELIVERY STRATEGIES.

Gastric cancer (GC) continues to be a significant global contributor to cancer-related mortality, primarily due to late-stage diagnoses, tumor heterogeneity, and the frequent emergence of therapeutic resistance. Despite advancements in surgical techniques, chemotherapy, targeted therapies, and immunotherapy, long-term survival rates remain unsatisfactory, underscoring the need for innovative, molecularly driven approaches. SiRNA has emerged as a promising gene-silencing tool capable of selectively downregulating oncogenic drivers and pathways associated with resistance via RNA interference. Preclinical studies using GC models demonstrate promising biological activity following siRNA-mediated suppression of various molecular targets - including CD44v6, Rac1, and ZNRD1-leading to reduced cell proliferation, inhibited migration and invasion, enhanced apoptosis, and increased chemosensitivity. However, the successful translation of siRNA-based strategies into clinical practice is fundamentally reliant on the development of efficient and safe delivery systems. Recent advancements in nanotechnology have enabled the development of multifunctional nanocarriers, including lipid-based nanoparticles, peptide-based systems, chitosanderived platforms, exosome-mimetic vesicles, layer-by-layer architectures, and stimuli-responsive theranostic nanoparticles. These engineered platforms are designed to enhance siRNA stability, improve tumor targeting, facilitate intracellular trafficking, and promote endosomal escape while minimizing off-target effects and immune activation. Preclinical findings suggest significant biological potential; however, additional research is required to address issues concerning biodistribution, safety, scalability, and regulatory standardization before clinical application. Overall, siRNA-based strategies may play a crucial role in the future development of precision-oriented therapeutic frameworks in GC research. Importantly, this review emphasizes the integration of molecular target selection with delivery system design in a GC-specific context. By systematically linking validated siRNA targets with corresponding nanocarrier strategies, this work provides a more application-oriented and translationally relevant perspective that is not typically addressed in conventional RNA interference or nanocarrier-focused reviews.

NANOCARRIER-BASED DELIVERY OF 5-FLUOROURACIL IN BREAST CANCER: TARGETING TUMOR MICROENVIRONMENT AND OVERCOMING CHEMORESISTANCE

Despite improvements in screening and treatment, breast cancer is still one of the most common cancers diagnosed in women globally and a major cause of cancer-related death. Although 5-fluorouracil (5-FU), a pyrimidine derivative, has long been used in systemic treatments for breast cancer, its low oral bioavailability, dose-limiting toxicities, and acquired resistance restrict its clinical efficacy. By enhancing drug stability, permitting controlled and stimuli-responsive release, and facilitating both passive and active tumor targeting, nanocarrier-based delivery platforms such as lipid-based systems, polymeric nanoparticles, dendrimers, nanogels, inorganic nanostructures, and hybrid nanoplatforms offer promising ways to get around these restrictions. This review synthesizes recent high-impact literature on nanocarrier-mediated delivery of 5-FU for breast cancer, covering pharmacological considerations, nanocarrier classes, targeted and co-delivery approaches, stimuli-responsive designs, challenges to clinical translation, and emerging trends such as personalized nanomedicine and AI-guided carrier optimization.

Lipid-based nanocarrier-enabled combination therapy for breast cancer: overcoming drug resistance toward precision oncology.