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  • Title: Self-crosslinkable and intracellularly decrosslinkable biodegradable micellar nanoparticles: A robust, simple and multifunctional nanoplatform for high-efficiency targeted cancer chemotherapy.
    Author: Zou Y, Fang Y, Meng H, Meng F, Deng C, Zhang J, Zhong Z.
    Journal: J Control Release; 2016 Dec 28; 244(Pt B):326-335. PubMed ID: 27245309.
    Abstract:
    Nanomedicines based on biodegradable micelles offer a most promising treatment for malignant tumors. Their clinical effectiveness, however, remains to be improved. Here, we report that self-crosslinkable and intracellularly decrosslinkable micellar nanoparticles (SCID-Ms) self-assembled from novel amphiphilic biodegradable poly(ethylene glycol)-b-poly(dithiolane trimethylene carbonate) block copolymer achieve high-efficiency targeted cancer chemotherapy in vivo. Interestingly, doxorubicin (DOX)-loaded SCID-Ms showed favorable features of superb stability, minimal drug leakage, long circulation time, triggered drug release inside the tumor cells, and an unprecedented maximum-tolerated dose (MTD) of over 100mg DOX equiv./kg in mice, which was at least 10 times higher than free drug. The in vivo studies in malignant B16 melanoma-bearing C57BL/6 mice revealed that DOX-SCID-Ms at a dosage of 30mg DOX equiv./kg could effectively suppress tumor growth and prolong mice survival time without causing obvious systemic toxicity. Moreover, DOX-SCID-Ms could be readily decorated with a targeting ligand like cRGD peptide. The biodistribution studies showed that cRGD20/DOX-SCID-Ms had a high tumor accumulation of 6.13% ID/g at 6h post injection, which was ca. 3-fold higher than that for clinically used pegylated liposomal doxorubicin (DOX-LPs). Accordingly, cRGD20/DOX-SCID-Ms exhibited significantly better therapeutic efficacy and lower side effects than DOX-LPs in B16 melanoma-bearing mice. These self-regulating biodegradable micellar nanoparticles offer a robust, multifunctional and viable nanoplatform for targeted cancer chemotherapy.
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