Yu Haitao, Yan Jianqin, Gao Song, Qiao Weili, Wang Maolong
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引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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.
Discussion: 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.
Conclusion: Future nanocarrier-based gene therapy for NSCLC should move beyond material innovation toward barrier-informed, resistance-matched, biomarker-guided, and clinically scalable precision nanomedicine.
期刊介绍：
Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases.
Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
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