Advancing design strategies in smart stimulus-responsive liposomes for drug release and nanomedicine

Abstract

Liposomes have emerged as the most clinically successful nanocarriers with good biocompatibility, low immunogenicity, and facile modification potential. However, their widespread application is limited by challenges associated with suboptimal drug release kinetics and poor bioavailability under complex physiological conditions. These limitations stem from the dual paradox of maintaining circulatory stability while enabling rapid drug release at target sites. Engineering of stimulus-responsive liposomal systems has been identified as a promising strategy for mitigating these biomedical delivery challenges. Such systems are designed to achieve spatiotemporally controlled drug release and nanomedicine in response to specific endogenous or exogenous stimulus, thereby enhancing therapeutic efficacy while minimizing systemic toxicity. A comprehensive understanding of the design principles and release mechanisms governing stimulus-responsive liposomes is essential for the rational development of advanced drug delivery systems. Therefore, this review systematically examines the design strategies for precise, stimulus-triggered drug release through a detailed analysis of the effects of liposome structure and composition on drug release, with particular emphasis on lipid component engineering for controlled release. Furthermore, it explores functionalization strategies, focusing on chemical modification approaches for stimulus-responsive behavior. The component-responsive design and functional modification strategies discussed herein provide a systematic framework for liposome research. Meanwhile, the fundamental understanding of stimulus-responsive liposomes is significantly advanced, thereby facilitating the development of more efficient and precise drug delivery and nanomedicine.

Keywords

conformational change / liposomes / stimulus-responsive drug release / structural cleavage

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