Nanoparticle-Based Delivery Strategies for Combating Drug Resistance in Cancer Therapeutics
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MDPI AG
Abstract
Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of addressing these challenges by enhancing intracellular drug accumulation, enabling targeted delivery and facilitating stimuli-responsive and controlled release. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying MDR and critically examines recent advances in nanoparticle strategies developed to overcome it. Various nanoparticle designs are analysed in terms of their structural and functional features, including surface modifications, active targeting ligands and responsiveness to tumour-specific cues. Particular emphasis is placed on the co-delivery of chemotherapeutic agents with gene regulators, such as siRNA, and the use of nanoparticles to deliver CRISPR/Cas9 gene editing tools as a means of re-sensitising resistant cancer cells. While significant progress has been made in preclinical settings, challenges such as tumour heterogeneity, limited clinical translation and immune clearance remain. Future directions include the integration of precision nanomedicine, scalable manufacturing and non-viral genome editing platforms. Collectively, nanoparticle-based drug delivery systems offer a multifaceted approach to combat MDR and hold great promise for improving therapeutic outcomes in resistant cancers.Description
Keywords
1112 Oncology and Carcinogenesis, 3211 Oncology and carcinogenesis, Multidrug resistance (MDR), ABC transporters, nanoparticles, cancer therapeutics, nucleic acid-based therapies, cancer immunotherapy, drug delivery, chemoresistance, mononuclear phagocyte system, nanocarriers, efflux pumps, gene editing, stimuli-responsive delivery, CRISPR/Cas9 delivery, nanomedicine
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Cancers, ISSN: 2072-6694 (Print); 2072-6694 (Online), MDPI AG, 17(16), 2628-2628. doi: 10.3390/cancers17162628
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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).