College of Chemistry, Chemical Engineering and Materials Science, State and Local Joint Engineering Laboratory for Functional Polymeric Materials, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Soochow University, Suzhou 215123, China.
ACS Appl Bio Mater. 2021 May 17;4(5):4422-4431. doi: 10.1021/acsabm.1c00177. Epub 2021 May 6.
In the treatment of tumor-targeted small-molecule anti-cancer drugs, antibody-mediated therapies, especially for antibody-drug conjugates (ADCs), have revealed great latent force. However, the therapeutic drugs provided by ADCs possess limitation. Considering that the combination of antibodies and nano-drugs can broaden their applicability in the field of tumor treatment, herein, we developed an antibody conjugated polymeric prodrug nanoparticles SAE-PEG--PBYP--CPT for targeted camptothecin (CPT) delivery to liver tumor cells. The diblock copolymer was composed of PEG and biodegradable polyphosphoester (PBYP) containing alkynyl groups in the side chain. A derivative of CPT (CPT--N) was bonded to the PBYP via "click" reaction. The diethyl squarate (SAE) in the terminal of PEG chain was used as a functional group to bond with CD147 monoclonal antibody (CD147 mAb). The particle size and size distribution of the both nanoparticles, with antibody binding (namely CD147-CPT NPs) and without antibody (abbreviated as CPT-loaded NPs), were measured by dynamic light scattering (DLS). The morphologies of both two kinds of nanoparticles were observed by transmission electron microscope (TEM). The results of X-ray photoelectron spectroscopy (XPS) showed that CD147 mAb had been coupled to the surface of CPT-loaded NPs. Endocytosis test indicated that CD147-CPT NPs had higher uptake rate and accumulation in HepG2 cells than those of CPT-loaded NPs without antibodies, due to CD147 mAb can specifically bind to CD147 protein overexpressed in HepG2 cells. We establish a method to bond monoclonal antibodies to anti-cancer polymeric prodrugs, and endow biodegradable polymeric prodrugs with precise targeting functions to liver cancer cells.
在肿瘤靶向小分子抗癌药物的治疗中,抗体介导的疗法,特别是抗体药物偶联物(ADC),显示出巨大的潜力。然而,ADC 提供的治疗药物存在局限性。考虑到抗体和纳米药物的结合可以拓宽它们在肿瘤治疗领域的适用性,在此,我们开发了一种抗体偶联的聚合物前药纳米粒子 SAE-PEG-PBYP-CPT,用于靶向递送到肝癌细胞的喜树碱(CPT)。该两亲性嵌段共聚物由聚乙二醇(PEG)和侧链含有炔基的可生物降解的聚膦酸酯(PBYP)组成。CPT 的衍生物(CPT-N)通过“点击”反应键合到 PBYP 上。PEG 链末端的二乙基丁烯二酸盐(SAE)被用作与 CD147 单克隆抗体(CD147 mAb)结合的官能团。通过动态光散射(DLS)测量了带有抗体结合(即 CD147-CPT NPs)和不带抗体(缩写为 CPT 负载 NPs)的两种纳米粒子的粒径和粒径分布。通过透射电子显微镜(TEM)观察了两种纳米粒子的形态。X 射线光电子能谱(XPS)的结果表明,CD147 mAb 已偶联到 CPT 负载 NPs 的表面。内吞试验表明,CD147-CPT NPs 比没有抗体的 CPT 负载 NPs 具有更高的摄取率和在 HepG2 细胞中的积累,这是因为 CD147 mAb 可以特异性结合 HepG2 细胞中过表达的 CD147 蛋白。我们建立了一种将单克隆抗体与抗癌聚合物前药结合的方法,并赋予可生物降解的聚合物前药对肝癌细胞的精确靶向功能。
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