Developing
controlled drug-release systems is imperative and valuable
for increasing the therapeutic index. Herein, we synthesized hypoxia-responsive
PEGylated (PEG = poly(ethylene glycol)) paclitaxel prodrugs by utilizing
azobenzene (Azo) as a cleavable linker. The as-fabricated prodrugs
could self-assemble into stable nanoparticles (PAP NPs) with high
drug content ranging from 26 to 44 wt %. The Azo group in PAP NPs
could be cleaved at the tumorous hypoxia microenvironment and promoted
the release of paclitaxel for exerting cytotoxicity toward cancer
cells. In addition, comparative researches revealed that the PAP NPs
with the shorter methoxy-PEG chain (molecular weight = 750) possessed
enhanced tumor suppression efficacy and alleviated off-target toxicity.
Our work demonstrates a promising tactic to develop smart and simple
nanomaterials for disease treatment.
Self-assembled prodrug nanoparticles with tumor-responsive capacity have great potential in tumor visualization and treatment. However, the nanoparticle formulas usually contain multiple components, especially polymeric materials, which result in various potential issues. Herein, we report an indocyanine green (ICG)-driven assembly of paclitaxel prodrugs integrating near-infrared fluorescence imaging and tumor-specific chemotherapy. By feat of the hydrophilic merit of ICG, paclitaxel dimer could form more uniformly monodispersed nanoparticles. This two-in-one strategy reinforces the complementary advantages, resulting in superior assembly behavior, robust colloidal stability, enhanced tumor accumulation as well as desirable near-infrared imaging and in vivo feedback of chemotherapy. The in vivo experiments validated the prodrug activation at tumor sites as evidenced by enhanced fluorescence intensity, potent tumor growth suppression, and reduced systemic toxicity compared with commercial Taxol. The universality of ICG potentiated strategy toward photosensitizers and fluorescence dyes was confirmed. This presentation provides deep insight into the feasibility of constructing clinical-close alternatives for improving antitumor efficacy.
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