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<p>Stimuli-responsive niosomal drug delivery nanosystems represent a forefront area in nanomedicine, combining the benefits of niosomes, vesicular structures composed of non-ionic surfactants, with the precision control of stimuli-responsive mechanisms. These nanosystems demonstrate superior biocompatibility, biodegradability, chemical stability, and cost-effective production, making them promising carriers for targeted and controlled drug release. Recent advances have focused on engineering niosomes that respond to diverse internal (pH, redox potential, enzymes) and external stimuli (temperature, light, magnetic fields), allowing site-specific drug delivery with enhanced therapeutic efficacy and minimized systemic toxicity. The integration of stimuli-responsive features addresses key challenges such as premature drug leakage, low bioavailability, and non-specific distribution, advancing applications in cancer therapy, ocular diseases, and other pathological conditions requiring precise spatiotemporal control of drug release. Despite significant progress, challenges remain, including optimizing stimulus sensitivity, large-scale manufacturability, stability during circulation, and comprehensive in vivo evaluation to ensure safety and efficacy. Moreover, an incomplete understanding of in vivo stimuli dynamics and heterogeneity poses barriers to clinical translation. Notably, prospects lie in multifunctional niosomal platforms combining targeting ligands, imaging agents, and combinatorial therapies, along with the development of smart hybrid nanosystems that synergistically exploit organic and inorganic components. Innovations in fabrication techniques and stimulus modalities are expected to expand the therapeutic landscape. This review aims to provide a critical analysis of the structural characteristics, stimuli-responsive mechanisms, recent technological advancements, and biomedical applications of niosomal drug delivery nanosystems. It highlights current challenges and prognosticates future research directions to facilitate their clinical translation and maximize their therapeutic potential in precision medicine.</p> Graphical Abstract <p></p>

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Stimuli-responsive niosomes: multifunctional platforms for overcoming drug resistance

  • 期刊论文

  • 发表日期：

    2026年6月22日

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  • Negar Nasri,
  • Shaghayegh Saharkhiz,
  • Atefeh Zarepour,
  • Arezoo Khosravi,
  • Ehsan Nazarzadeh Zare,
  • Rajender S. Varma,
  • Siavash Iravani,
  • Pooyan Makvandi

摘要

Stimuli-responsive niosomal drug delivery nanosystems represent a forefront area in nanomedicine, combining the benefits of niosomes, vesicular structures composed of non-ionic surfactants, with the precision control of stimuli-responsive mechanisms. These nanosystems demonstrate superior biocompatibility, biodegradability, chemical stability, and cost-effective production, making them promising carriers for targeted and controlled drug release. Recent advances have focused on engineering niosomes that respond to diverse internal (pH, redox potential, enzymes) and external stimuli (temperature, light, magnetic fields), allowing site-specific drug delivery with enhanced therapeutic efficacy and minimized systemic toxicity. The integration of stimuli-responsive features addresses key challenges such as premature drug leakage, low bioavailability, and non-specific distribution, advancing applications in cancer therapy, ocular diseases, and other pathological conditions requiring precise spatiotemporal control of drug release. Despite significant progress, challenges remain, including optimizing stimulus sensitivity, large-scale manufacturability, stability during circulation, and comprehensive in vivo evaluation to ensure safety and efficacy. Moreover, an incomplete understanding of in vivo stimuli dynamics and heterogeneity poses barriers to clinical translation. Notably, prospects lie in multifunctional niosomal platforms combining targeting ligands, imaging agents, and combinatorial therapies, along with the development of smart hybrid nanosystems that synergistically exploit organic and inorganic components. Innovations in fabrication techniques and stimulus modalities are expected to expand the therapeutic landscape. This review aims to provide a critical analysis of the structural characteristics, stimuli-responsive mechanisms, recent technological advancements, and biomedical applications of niosomal drug delivery nanosystems. It highlights current challenges and prognosticates future research directions to facilitate their clinical translation and maximize their therapeutic potential in precision medicine.

Graphical Abstract