| The sub-lethal drug concentration in cancer therapy always occurred because of the systematic barriers existed in the drug-resistant tumor microenvironment.To circumvent this issue,accurate and rapid drug release in cancer cells is crucial to provide optimum drug concentrations,preventing P-glycoprotein pumping out,increasing efficiency of chemotherapy,and destroying cancer cells without respite.In this contribution,we reported a helical chains functionalized polymeric micelles for the co-delivery of dyes and drugs for cancer imaging and therapy by taking advantage of pH,reduction,and UV light multiple synergistic triggers.The positively charged guanidine groups modified hydrophilic helical chains had a similar structure to cell penetrating peptides,which played an important role on their interacting 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 the micelles with acidic medium or reductive environment.Moreover,an enhanced rapid drug release was realized if all the three stimulus were performed on the micelles simultaneously,which exactly avoided the insufficient drug concentration in cancer cells brought from the 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-ofconcept is operated through multiple stimuli responsive drug release,showing promise for minimizing side effects,improving drug utilization efficiency,and having a bright prospect in biomedical practice. |
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