Carboxybetaine-Based Zwitterionic Polymer Nanogels with Long Blood Circulation for Cancer Therapy

Abstract

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.

Stimuli‐Responsive and Multifunctional Nanogels in Drug Delivery

“…The produced nanogels exhibit good long-term blood circulation without stimulating immunological reactions. [189] DOX-loaded PCBMA nanogels have a notable tumour suppression impact in mouse colorectal cancer (CC) models by extending circulation and enhancing tumour aggregation through passive targeting, which may offer a delivery method with considerable potential in cancer therapy. Intravenous boron neutron capture treatment (BNCT) employing hydrophobized boron oxide nanoparticle (HBNGs) reduced tumour volume without significantly reducing body weight, and three months after full shrinkage, no signs of tumour recurrence were seen.…”

Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation

“…Zwitterionic polymers carry equal numbers of anionic and cationic charges in close spatial proximity, leading to extremely high levels of hydration and therefore excellent non-fouling properties [ 41 ]. Though these materials are non-biodegradable they have shown excellent biocompatibility in vivo [ [42] , [43] , [44] ]. In addition, due to their very weak interaction with any surrounding (macro)molecules, they have been found to penetrate well into tumor tissue [ 45 , 46 ] – a property that should also translate to cartilage.…”

Zwitterionic Polymer-Decorated Lipid Nanoparticles for mRNA Delivery in Mammalian Cells

“…Many polymers are qualified as alternatives to PEG, such as poly­(oxazolines), − poly­(zwitterions), − polysaccharides, , poly­(vinylpyrrolidones) , and polypeptoids, − due to their hydrophilicity, biocompatibility, nonimmunogenicity, or antifouling properties. In 2020, lipopolymers of peptide18/peptide563-poly­(2-ethyl-2-oxazo-line)-dioleoylphosphatidyl-ethanolamine (P18/P563-PEtOx-DOPE) were synthesized and fabricated into liposomes targeting breast cancer cells and prostate cancer cells .…”