Thermosensitive polymer-conjugated albumin nanospheres as thermal targeting anti-cancer drug carrier
Thermosensitive polymer-conjugated albumin nanospheres as thermal targeting anti-cancer drug carrier
复制标题
热敏聚合物共轭白蛋白纳米球作为热靶向抗癌药物载体
DOI：
10.1016/j.ejps.2008.07.006
复制
发表时间：
2008-11-15
影响因子：
4.6
通讯作者：
Wan, Jinpei
中科院分区：
文献类型：
--
作者：
Shen, Zheyu;Wei, Wei;Wan, Jinpei
将热敏Poly(N-isopropylacrylamide-co-acrylamide-co-allylamine)(PNIPAM-AAm-AA)偶联到白蛋白纳米球(AN)表面，制备了一种新型热靶向抗癌药物载体。第一步采用解溶技术成功制备了粒径小于200 nm、粒径分布较窄的纳米粒子。第二步通过自由基聚合法合成了不同相对分子质量(M-w)的PNIPAM-AAm-AA，并将其偶联到AN的表面。在制备过程中，抗癌药物阿霉素(ADR)被包埋在AN和PAN中。与AN相比，PAN在胰酶溶液中的ADR释放速率较慢，且随PNIPAM-AAm-AA偶联量(毛发密度)或M-w(毛长)的增加而降低。此外，在PNIPAM-AAm-AA的浊点温度(T-cp)以上，由于毛状温敏聚合物的收缩，ADR从PAN中释放得更快。为了验证PAN在体内的热靶向性，将PAN与HepG2细胞孵育。正如预期的那样，PAN可以靶向高于PNIPAM-AAM-AA的T-cp的癌细胞，而不能低于T-cp。这些结果可能反映了PAN可能选择性地积聚在由于局部热疗而维持在生理温度以上的实体瘤上。(C)2008爱思唯尔B.V.保留所有权利。
Thermosensitive Poly(N-isopropylacrylamide-co-acrylamide-co-allylamine) (PNIPAM-AAm-AA)-conjugated albumin nanospheres (PAN) was developed as a new thermal targeting anti-cancer drug carrier by conjugating PNIPAM-AAm-AA on the surface of albumin nanospheres (AN). AN with diameter below 200 nm and narrow size distribution was successfully prepared in the first step with desolvation technique. PNIPAM-AAm-AA with different molecular weight (M-w) was synthesized in the second step by radical polymerization and conjugated onto the surface of AN. Anti-cancer drug adriamycin (ADR) was then entrapped into the AN and PAN during the particle preparation. Compared with AN, the release rate of ADR from PAN in trypsin solution was slower, and decreased with increasing the conjugation amounts (hairy density) or M-w of PNIPAM-AAm-AA (hairy length). Moreover, the release of ADR from PAN above the cloud-point temperature (T-cp) of PNIPAM-AAm-AA became faster due to shrinkage of hairy thermosensitive polymer. To testify the thermal targetability in vivo, PAN was incubated with HepG2 cells. As expected, PAN can target cancer cells above the T-cp of PNIPAM-AAm-AA, whereas it cannot below the T-cp. These results might reflect that PAN may selectively accumulate onto solid tumors that are maintained above physiological temperature due to local hyperthermia. (C) 2008 Elsevier B.V. All rights reserved.