Sun Haotian, Yan Lingyue, Chang Michael Yu Zarng, Carter Kevin A, Zhang Runsheng, Slyker Leigh, Lovell Jonathan F, Wu Yun, Cheng Chong
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.
Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.
Nanoscale Adv. 2019;1(7):2761-2771. doi: 10.1039/c9na00282k. Epub 2019 May 27.
A multifunctional biodegradable brush polymer-drug conjugate (BPDC) is developed for the co-delivery of hydrophobic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) chemotherapeutics, as well as a tumor imaging agent. A novel ternary copolymer of conventional, acetylenyl-functionalized and allyl-functionalized lactides is prepared to serve as the backbone precursor of BPDC. Acetylenyl groups of the copolymer are then reacted with poly(ethylene glycol) (PEG) side chains and cyanine5.5, a fluorescent probe, azide-alkyne click reactions. Subsequently, the allyl groups of the yielded PEG-grafted brush polymer are used to covalently link PTX and GEM onto the backbone thiol-ene click reactions. The resulting BPDC exhibits an average hydrodynamic diameter of 111 nm. Sustained and simultaneous release of PTX and GEM from the BPDC is observed in phosphate buffered saline, with the release of PTX showing sensitivity in mild acidic conditions. studies using MIA PaCa-2 human pancreatic cancer cells illustrate the cellular uptake and cytotoxicity of the BPDC. , the BPDC possesses long blood circulation, tumor accumulation, and enables optical tumor imaging. Further development and testing is warranted for multifunctional conjugated brush polymer systems that integrate combination chemotherapies and imaging.
一种多功能可生物降解的刷状聚合物-药物偶联物（BPDC）被开发用于疏水性紫杉醇（PTX）和亲水性吉西他滨（GEM）化疗药物以及肿瘤成像剂的共递送。制备了一种由常规、乙炔基官能化和烯丙基官能化丙交酯组成的新型三元共聚物，用作BPDC的主链前体。然后，通过叠氮-炔点击反应，使共聚物的乙炔基与聚乙二醇（PEG）侧链和荧光探针花菁5.5反应。随后，通过硫醇-烯点击反应，将所得PEG接枝刷状聚合物的烯丙基用于将PTX和GEM共价连接到主链上。所得的BPDC的平均流体动力学直径为111nm。在磷酸盐缓冲盐水中观察到PTX和GEM从BPDC中持续且同时释放，PTX的释放在轻度酸性条件下表现出敏感性。使用MIA PaCa-2人胰腺癌细胞的研究说明了BPDC的细胞摄取和细胞毒性。此外，BPDC具有长循环、肿瘤蓄积能力，并能够进行光学肿瘤成像。对于整合联合化疗和成像的多功能共轭刷状聚合物系统，有必要进行进一步的开发和测试。
