Low-power and low-drug-dose photodynamic chemotherapyviathe breakdown of tumor-targeted micelles by reactive oxygen species


    loading  Checking for direct PDF access through Ovid

Abstract

Tumor-targeted delivery of anticancer agents using nanocarriers has been explored to increase the therapeutic index of cancer chemotherapy. However, only a few nanocarriers are clinically available because the physiological complexity often compromises their ability to target, penetrate, and control the release of drugs. Here, we report a method which dramatically increases in vivo therapeutic drug efficacy levels through the photodynamic degradation of tumor-targeted nanocarriers. Folate-decorated poly(ethylene glycol)-polythioketal micelles are prepared to encapsulate paclitaxel and porphyrins. Photo-excitation generates reactive oxygen species within the micelles to cleave the polythioketal backbone efficiently and facilitate drug release only at the illuminated tumor site. Intravenous injection of a murine xenograft model with a low dose of paclitaxel within the micelles, one-milligram drug per kg (mouse), corresponding to an amount less than that of Taxol by one order of magnitude, induces dramatic tumor regression without any acute systemic inflammation responses or organ toxicity under low-power irradiation (55 mW cm−2) at 650 nm.Graphical abstractHighlightsPhotodynamically-induced drug delivery under low light intensity and low drug doseROS-scavenging micelles releasing paclitaxel under 650 nm light irradiationDramatic reduction of IC50 of paclitaxel to 4.27% of the reported valueEfficient ROS consumption by PPADT micellesOnly 5% of maximum tolerated dose of paclitaxel for tumor suppression

    loading  Loading Related Articles