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Given the advantages of antifouling capacity and good biocompatibility, zwitterionic polymers have been profoundly applied for drug delivery to improve the pharmacokinetics profile. Here, a zwitterionic polymer (poly (carboxybetaine methacrylate) (PCBMA)) nanogel was fabricated by one-step reflux precipitation polymerization for doxorubicin (DOX) loading. The obtained nanogels display favorable long blood circulation without priming immune responses as a result of the introduction of the zwitterionic group. Meanwhile, the disulfide bonds deriving from the crosslinker endow nanogels with excellent glutathione-responsive degradation and sufficient drug release under a reduction environment. The carboxylate groups originating from carboxybetaine provide modification sites to conjugate with fluorescent dye to achieve labeling and biodistribution tracking. Overall, under the significantly prolonging circulation and enhanced tumor accumulation through passive targeting, DOX-loaded PCBMA nanogels show a noticeable tumor inhibition effect in mouse colorectal cancer models, which may provide a delivery vehicle with great promise in cancer therapy.

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