A Smart Nano‐Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy

AbstractNano‐prodrugs usually involve a multistep synthesis which largely compromises their benefits. Here, a smart nano‐prodrug platform with reactive drug loading, superb stability, and triggered drug release is reported for targeted melanoma therapy. cRGD‐decorated polymersomal mertansine prodrug (cRGD‐PS‐DM1) is readily fabricated from cRGD‐functionalized poly(ethylene glycol)‐b‐poly(trimethylene carbonate‐co‐dithiolane trimethylene carbonate) with simultaneous loading of mertansine (DM1) via thiol–disulfide exchange reaction and disulfide cross‐linking of polymersomal membrane. cRGD‐PS‐DM1 exhibits a size of ≈100 nm, little drug leakage, and fast DM1 release in the presence of 2 × 10−3–10 × 10−3 m glutathione. Tetrazolium‐based colorimetric assay (MTT) and confocal microscopy studies confirm effective homing of cRGD‐PS‐DM1 to αvβ3 overexpressing B16F10 melanoma cells. Notably, the in vivo studies show that cRGD‐PS‐DM1 has a greatly improved toleration as compared with free DM1 and effectively inhibits tumor growth and extends the survival time of B16F10 melanoma‐bearing mice. cRGD‐PS‐DM1 nano‐prodrug with reactive drug loading and multifunction provides an advanced nanomedicine for cancer therapy. image