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

Abstract

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 αvβ3 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.