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Nanocarriers with responsibility and surface functionality of targeting molecules have been widely used to improve therapeutic efficiency. Hence, we report the assembly of pH-responsive and targeted polymer nanoparticles (NPs) composed of poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) as the core and poly(carboxybetaine methacrylate) (PCBMA) as the shell, functionalized with cyclic peptides containing Arginine-Glycine-Aspartic acid- D -Phenylalanine-Lysine (RGD). The resulting polymer NPs (PDPA@PCBMA-RGD NPs) can maintain the pH-responsivity of PDPA (pKa ~6.5) and low-fouling property of PCBMA that significantly resist non-specific interactions with RAW 264.7 and HeLa cells. Meanwhile, PDPA@PCBMA-RGD NPs could specifically target α v β 3  integrin-expressed human glioblastoma (U87) cells. The pH-responsiveness and low-fouling properties of PDPA@PCBMA NPs are comparable to PDPA@poly(ethylene glycol) (PDPA@PEG) NPs, which indicates that PCBMA is an alternative to PEG for low-fouling coatings. The advantage of PDPA@PCBMA NPs lies in the presence of carboxyl groups on their surfaces for further modification (e.g., RGD functionalization for cell targeting). The reported polymer NPs represent a new carrier that have the potential for targeted therapeutic delivery.

Antifouling and pH-Responsive Poly(Carboxybetaine)-Based Nanoparticles for Tumor Cell Targeting