Abstract
Targeted delivery of drugs in therapeutic applications is gaining traction in treating various diseases. However, its practicality is challenged by uncontrolled drug release. We present here a novel dual-trigger polyamidoaminebased crosslinked micelle vector that releases therapeutic drugs in response to triggers. The degradation of micelles can be controlled by redox and MMP-2 enzymatic activities. Such a system can achieve greater specificity for drug release than most recently reported micelle systems. Cytotoxicity tests of the micelles showed that they posed significantly lower toxicity towards normal cells as normal cells have relatively lower concentration of MMP-2 enzyme to disintegrate the micelles. The paclitaxel-conjugated micelles were effective in inducing apoptosis and cell cycle arrest in MDA-MB-231 cancer cells. The results demonstrated that the degradation of polyamidoamines could be fine-tuned by an enzyme-active peptide, thus increasing the anti-tumour efficacy and pave the way for development of highly controllable targeted drug delivery platforms.
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