Advancements in Polymeric Nanocarriers: Cisplatin and siRNA-Based Strategies for Tumor Growth Suppression and Overcoming Resistance in Non-Small Cell Lung Cancer
نویسندگان
1 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
2 Department of Obstetrics and Gynaecology, Samarkand State Medical University, Samarkand, Republic of Uzbekistan
3 Department of Children’s Diseases, Tashkent State Medical University, Tashkent, Republic of Uzbekistan
4 Department of Oncolgy, Andijan State Medical Institute, Andijan, Uzbekistan
5 Department of Language, Central Asian Medical University, Fergana, Uzbekistan
6 Department of Economy, Mamun University, Uzbekistan
7 Ferghana Medical Institute of Public Health, Uzbekistan
8 Department of Anatomy and Clinical Anatomy, Bukhara State Medical Institute, Bukhara, Republic of Uzbekistan
9 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
10 Department of Chemistry and Biology, Tashkent International Kimyo University, Tashkent, Republic of Uzbekistan
11 Termez State University,Uzbekistan
12 Department of Pharmacology, Bukhara State Medical Institute named after Abu Ali ibn Sino, Uzbekistan
13 Department of Fruits and Vegetables, Urganch State University, Uzbekistan
doi
10.22052/JNS.2025.02.020چکیده
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, with a high prevalence and poor prognosis due to inherent and acquired resistance mechanisms. Cisplatin remains one of the most commonly used chemotherapeutic agents for NSCLC, functioning primarily through DNA damage-induced apoptosis. However, the emergence of resistance pathways such as increased DNA repair, drug efflux mechanisms, and activation of survival signaling pathways significantly limits its long-term efficacy. To address this challenge, small interfering RNA (siRNA) therapy has gained attention as a targeted approach to silence key genes responsible for cisplatin resistance, enhancing the drug’s cytotoxic effects. Despite its potential, efficient delivery of siRNA remains a major hurdle due to its instability, rapid enzymatic degradation, and low cellular uptake. Polymeric nanocarriers have emerged as promising vehicles for drug delivery, offering controlled release, enhanced cellular uptake, and improved bioavailability of both cisplatin and siRNA. Their ability to encapsulate and protect therapeutic agents enables synergistic effects in tumor suppression and resistance modulation. Various polymer-based delivery platforms, including poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG)-modified systems, and chitosan-based nanoparticles, have demonstrated improved treatment outcomes in preclinical studies. These nanocarriers not only facilitate targeted drug delivery but also enhance the therapeutic index by reducing systemic toxicity. This review provides a comprehensive analysis of the advancements in polymeric nanocarriers for co-delivery of cisplatin and siRNA in NSCLC treatment. It explores the molecular mechanisms of tumor growth and drug resistance, the design and functionalization of polymeric carriers, and their role in overcoming treatment limitations. By discussing preclinical and clinical findings, this work aims to highlight the potential of these strategies for improving patient outcomes and addressing key challenges in NSCLC therapy.
