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.

两性离子氨基酸聚合物（ZAPs）对癌细胞上过表达的氨基酸转运蛋白（AATs）表现出生物相容性和识别能力。它们是用于癌症化疗的基于纳米颗粒的纳米药物中潜在的癌症靶向配体。在此，通过使用包含聚（甲基丙烯酸谷氨酰胺）（pGlnMA）作为亲水嵌段的两亲性嵌段共聚物稳定纳米乳液的形成，制备了聚（甲基丙烯酸谷氨酰胺）接枝的核交联颗粒（pGlnMA - CCP）。通过动态光散射、X射线散射和透射电子显微镜精确阐明了接枝聚合物的链构象和pGlnMA - CCP的颗粒结构。pGlnMA - CCP分别通过AAT介导的机制对癌细胞和肿瘤球表现出主动的细胞摄取和深度穿透行为。pGlnMA - CCP的体内药代动力学实际上与覆盖有聚（甲基丙烯酸聚乙二醇酯）（pPEGMA）的CCP相当，pPEGMA抑制蛋白质吸附并延长血液滞留时间，这意味着pGlnMA的生物相容性与pPEGMA相似。此外，pGlnMA - CCP在癌组织中的积累水平高于pPEGMA体系。结果表明，通过将pGlnMA接枝到纳米颗粒上可以获得癌症靶向性、肿瘤渗透性、有效的肿瘤积累和生物相容性等特性，这表明pGlnMA作为癌症靶向纳米药物的配体具有很高的潜力。