Zwitterionic Amino Acid Polymer-Grafted Core-Crosslinked Particle toward Tumor Delivery.

Zwitterionic amino acid polymers (ZAPs) exhibit biocompatibility and recognition capability for amino acid transporters (AATs) overexpressed on cancer cells. They are potential cancer-targeting ligands in nanoparticle-based nanomedicines utilized in cancer chemotherapy. Here, a poly(glutamine methacrylate) (pGlnMA)-grafted core-crosslinked particle (pGlnMA-CCP) is prepared through the formation of nanoemulsions stabilized using amphiphilic block copolymers comprising pGlnMA as the hydrophilic block. The chain conformation of the grafted polymer and the particle structure of pGlnMA-CCP are precisely elucidated by dynamic light scattering, X-ray scattering, and transmission electron microscopy. pGlnMA-CCP demonstrates active cellular uptake and deep penetration behaviors for cancer cells and spheroids, respectively, via an AAT-mediated mechanism. The in vivo pharmacokinetics of pGlnMA-CCP is practically comparable to those of a CCP covered with poly(polyethylene glycol methacrylate) (pPEGMA), which inhibits protein adsorption and prolongs blood retention, implying that the biocompatible properties of pGlnMA are similar to those of pPEGMA. Furthermore, pGlnMA-CCP accumulates in cancer tissues at a higher level than that of pPEGMA systems. The results demonstrate that the properties of cancer targetability, tumor permeability, efficient tumor accumulation, and biocompatibility can be obtained by grafting pGlnMA onto nanoparticles, suggesting a high potential of pGlnMA as a ligand for cancer-targeting nanomedicines.