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<p>Multidrug resistance (MDR) remains a major obstacle to effective cancer chemotherapy. MDR in cancer frequently results in therapeutic failure, tumor relapse, and poor clinical outcomes. Nanoparticles (NPs)-based drug delivery systems have emerged as promising strategies to overcome MDR by improving drug solubility, enhancing tumor accumulation, and inhibiting efflux transporter-mediated drug efflux. Among the various functional excipients used in nanomedicine, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has gained considerable attention due to its dual role as a pharmaceutical excipient and a biologically active MDR modulator. This review critically examines the emerging role of TPGS-based NPs as multifunctional platforms for overcoming MDR in cancer therapy. First, the molecular mechanisms by which TPGS reverses drug resistance are discussed. Subsequently, recent advances in the development of diverse TPGS-NPs are systematically reviewed with respect to their design strategies and therapeutic performance in MDR tumor models. In addition, the potential of TPGS-NPs for combinatorial drug delivery and chemosensitization is highlighted as a promising strategy to enhance anticancer efficacy. Finally, current challenges that hinder clinical translation are discussed, together with perspectives for future research. Overall, this review highlights that TPGS-NPs provide a versatile and multifunctional NPs platform capable of simultaneously improving drug delivery and modulating resistance mechanisms, thereby offering significant promise for advancing therapeutic strategies against MDR-associated cancers.</p>

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Harnessing TPGS-based Nanoparticles to Overcome Multidrug Resistance in Cancer

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Karthik Mangu,
  • Aryan Varma Nadimpalli,
  • Satvik Reddy Chenna,
  • Md. Rizwanullah

摘要

Multidrug resistance (MDR) remains a major obstacle to effective cancer chemotherapy. MDR in cancer frequently results in therapeutic failure, tumor relapse, and poor clinical outcomes. Nanoparticles (NPs)-based drug delivery systems have emerged as promising strategies to overcome MDR by improving drug solubility, enhancing tumor accumulation, and inhibiting efflux transporter-mediated drug efflux. Among the various functional excipients used in nanomedicine, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has gained considerable attention due to its dual role as a pharmaceutical excipient and a biologically active MDR modulator. This review critically examines the emerging role of TPGS-based NPs as multifunctional platforms for overcoming MDR in cancer therapy. First, the molecular mechanisms by which TPGS reverses drug resistance are discussed. Subsequently, recent advances in the development of diverse TPGS-NPs are systematically reviewed with respect to their design strategies and therapeutic performance in MDR tumor models. In addition, the potential of TPGS-NPs for combinatorial drug delivery and chemosensitization is highlighted as a promising strategy to enhance anticancer efficacy. Finally, current challenges that hinder clinical translation are discussed, together with perspectives for future research. Overall, this review highlights that TPGS-NPs provide a versatile and multifunctional NPs platform capable of simultaneously improving drug delivery and modulating resistance mechanisms, thereby offering significant promise for advancing therapeutic strategies against MDR-associated cancers.