Aug 2026· Experimental oncology· Vol 48 2, pp.
81-97
· 0 citations· 56 references
Medicine
TL;DR
Overall, siRNA-based strategies may play a crucial role in the future development of precision-oriented therapeutic frameworks in GC research, and this review emphasizes the integration of molecular target selection with delivery system design in a GC-specific context.
Abstract
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.
Abstract Breast cancer remains one of the leading causes of cancer-related mortality worldwide, with its marked molecular heterogeneity and therapeutic resistance continuing to limit long-term clinical success. Although advances in targeted therapies have improved patient outcomes, tumor recurrence, systemic toxicity, and drug resistance remain major clinical challenges. MicroRNAs (miRNAs) have emerged as promising therapeutic molecules because they regulate multiple oncogenic pathways involved in proliferation, apoptosis, epithelial–mesenchymal transition, metastasis, and therapy resistance. Preclinical studies have demonstrated that restoring tumor-suppressive miRNAs or inhibiting oncogenic miRNAs can suppress tumor growth, reduce metastatic potential, and enhance treatment sensitivity. However, their clinical application is hindered by poor stability, rapid enzymatic degradation, limited cellular uptake, and inefficient intracellular delivery. Recent advances in nanomedicine have enabled the development of multifunctional nanoparticle platforms that effectively address these limitations. Lipid nanoparticles, polymeric nanoparticles, dendrimers, and inorganic nanocarriers have demonstrated the ability to protect miRNAs from degradation, prolong systemic circulation, enhance tumor-specific accumulation, facilitate cellular uptake, and promote endosomal escape for efficient cytoplasmic release. Moreover, targeted and stimuli-responsive nanocarriers, as well as combination strategies integrating miRNAs with conventional therapeutics, have shown encouraging therapeutic efficacy in preclinical breast cancer models. This review summarizes recent advances in nanoparticle-mediated miRNA delivery systems for breast cancer, highlighting the biological roles of therapeutic miRNAs, the design and performance of current nanocarriers, and their translational potential. Current challenges and future perspectives for the clinical implementation of miRNA-based nanomedicine are also discussed. Overall, nanoparticle-enabled miRNA therapeutics represent a promising platform for advancing precision medicine and next-generation personalized treatment strategies for breast cancer.
Övünç Efe Lukumci, D. Cansaran-Duman, Pelin Mutlu· International Journal of Nan...· 0 citations
RNA-based theranostic strategies show promising potential for glioma therapy, however, further optimization of delivery systems, improved safety profiles, and successful clinical translation remain necessary.
Challenges such as scalable production, cargo heterogeneity, and regulatory considerations remain, but ongoing advances in exosome engineering and patient-derived vesicles are poised to overcome these barriers.
Amr Ali Mohamed Abdelgawwad El-Sehrawy, Hassan Youssef Hussein, O. Nematov et al.· DARU Journal of Pharmaceutic...· 0 citations
Overall, nanomedicine offers a multifaceted and promising approach to overcome MDR in breast cancer; however, further translational and clinical studies are required to fully realize its therapeutic potential.
Mohit Kumar, Tejaswi, Rohit Bangwal et al.· Journal of the Egyptian Nati...· 0 citations
A comprehensive overview of emerging and targeted therapeutic strategies in colorectal cancer, with emphasis on their molecular basis and clinical relevance, highlights a shift toward precision oncology for improved management of colorectal cancer.
Debgopal Ganguly, Ananta Choudhury, H. Deka et al.· Clinical and Translational O...· 0 citations
Lung cancer remains a leading cause of cancer-related mortality worldwide,
and non-small cell lung cancer (NSCLC) is the major histological subtype. Although chemotherapy,
molecular targeted therapy, and immune checkpoint blockade have improved outcomes in
selected patients, therapeutic resistance, tumor heterogeneity, systemic toxicity, and limited responsiveness
still restrict durable clinical benefit. This review critically evaluates nanocarrier-mediated
gene delivery for gene regulation, combination therapy, and resistance reversal in NSCLC.
As a narrative review, this article integrates studies on nucleic acid nanomedicine relevant
to NSCLC using a barrier-payload-resistance-translation framework, focusing on payload
compatibility, intracellular trafficking, endosomal escape, immune safety, pharmacokinetics, biodistribution,
and translational feasibility.
Small interfering RNA (siRNA), microRNA (miRNA), antisense oligonucleotides (ASOs),
and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9
(CRISPR/Cas9) systems can modulate oncogenic signaling, resistance-associated pathways, and the
tumor immune microenvironment. However, effective delivery requires overcoming nuclease degradation,
mononuclear phagocyte clearance, heterogeneous tumor accumulation, stromal barriers,
inefficient cellular uptake, insufficient endosomal escape, immune activation, and uncertain pharmacokinetic
and biodistribution profiles.
This review discusses lipid-based, polymeric, inorganic, bio-derived, and viral systems
according to payload compatibility, intracellular delivery requirements, safety, and clinical feasibility.
Particular emphasis is placed on resistance mechanisms beyond classical multidrug efflux, including
epithelial-mesenchymal transition (EMT), cancer stem cell-associated resistance, DNA
damage repair, bypass activation of targeted therapy pathways, immune escape, and metabolic reprogramming.
Future nanocarrier-based gene therapy for NSCLC should move beyond material innovation
toward barrier-informed, resistance-matched, biomarker-guided, and clinically scalable
precision nanomedicine.
Hai-Tao Yu, Jian-Qin Yan, Song Gao et al.· Current Gene Therapy· 0 citations
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