Abstract
Biocompatible nanosystems based on polymeric materials are promising drug delivery nanocarrier candidates for antitumor therapy. However, the efficacy is unsatisfying due to nonspecific accumulation and drug release of the nanoparticles in normal tissue. Recently, the nanosystems that can be triggered by tumor-specific stimuli have drawn great interest for drug delivery applications due to their controllable drug release properties. In this review, various polymers and external stimuli that can be employed to develop stimuli-responsive polymeric nanosystems are discussed, and finally, we delineate the challenges in designing this kind of Nanomedicine to improve the therapeutic efficacy.
Highlights
The peptide substrates that can be recognized by tumor-overexpressed proteases such as MMP2/9 and cathepsin B (CatB) have been widely employed to design protease-responsive polymeric drug delivery systems, [28,110,111,112] and several of them are in clinical trials [112,113,114]
We summarized a variety of polymers that have been extensively explored for polymeric drug delivery nanosystems development, and discussed both endogenous and exogenous stimuli-responsive drug nanocarriers that are reported for controlled drug release in antitumor therapy
The pharmaceutical properties of the loaded drugs can be improved and the therapeutic efficacy would be enhanced by controlling the drug release at the site of interest while minimizing the undesired side effects
Summary
Owing to the overexpression of many proteases in cancer and their key roles in tumor progression, a number of protease-responsive polymeric nanosystems have been developed by integrating polymer materials with peptide modules to impart the nanoparticles with protease-selectivity, allowing for protease-unlocked drug release at tumor sites [16,27,28,29]. Ultrasound is a widely explored stimulus for activatable polymeric drug delivery nanocarriers development due to the non-invasiveness and deep tissue penetration [38,39,40]. These stimuli-responsive polymeric nanosystems have shown great potential in improving the tumor-specificity of drug delivery and enhancing the anti-tumor efficacy. Various polymeric drug delivery nanoplatforms that can be triggered by external stimuli including endogenous and exogenous targets are surveyed
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