Facile fabrication of positively-charged helical poly(phenyl isocyanide) modified multi-stimuli-responsive nanoassembly capable of high efficiency cell-penetrating, ratiometric fluorescence imaging, and rapid intracellular drug release

Literature Information

Publication Date 2018-07-17
DOI 10.1039/C8PY00865E
Impact Factor 5.582
Authors

Wen-Ming Zhang, Jian Zhang, Zhu Qiao, Huan-Ying Liu, Zong-Quan Wu, Jun Yin


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Abstract

Sub-lethal drug concentrations in cancer therapy have always occurred because of the systematic barriers existing in the drug-resistant tumor microenvironment. To circumvent this issue, accurate and rapid drug release in cancer cells is crucial for providing optimum drug concentrations, preventing P-glycoprotein pumping out, increasing the efficiency of chemotherapy, and destroying cancer cells without respite. In this contribution, we report helical chain functionalized polymeric micelles for the co-delivery of dyes and drugs for cell imaging and therapy by taking advantage of pH, oxidation, and UV light multiple synergistic triggers. The positively charged guanidine group modified hydrophilic helical chains have a similar structure to cell penetrating peptides, which play an important role in their interaction with lipid bilayers in cell membranes and enhance subsequent cell internalization. The resultant complex nanoassembly has a preferable size of ∼185 nm and strong stability in aqueous solution, which is beneficial to long-term blood circulation and efficient extravasation from tumoral vessels. In conditions mimicking the extracellular environment, the complex nanoassembly showed a slow cargo release rate, while an accelerated release was observed after incubation of the micelles with an acidic medium or reductive environment. Moreover, an enhanced rapid drug release was realized if all three stimuli were performed on the micelles simultaneously, which exactly avoided insufficient drug concentration in cancer cells brought about by poor drug release or drug efflux pumps. The drug-loaded nanoassembly showed a devastating cytotoxicity against cancer cells, whereas blank samples were found to be non-toxic. This proof-of-concept is operated through multiple stimuli responsive drug release, showing promise for minimizing side effects, improving drug utilization efficiency, and having bright prospects in biomedical practice.

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