Docetaxel-encapsulating small-sized polymeric micelles with higher permeability and its efficacy on the orthotopic transplantation model of pancreatic ductal adenocarcinoma.
Docetaxel-encapsulating small-sized polymeric micelles with higher permeability and its efficacy on the orthotopic transplantation model of pancreatic ductal adenocarcinoma.
复制标题
DOI：
10.3390/ijms151223571
复制
发表时间：
2014-12-17
影响因子：
5.6
通讯作者：
Gao Z
中科院分区：
文献类型：
--
作者：
Li Y;Li P;Jin M;Jiang C;Gao Z
胰腺导管腺癌(PDAC)引起致密的间质反应，由于周细胞覆盖血管窗而阻塞血管通路。通过这种方式，PDAC基质有助于化疗耐药，而载铂的小尺寸纳米载体被用来解决不适合负载多西紫杉醇(DTX)的问题。在本研究中，我们使用聚(d，L-丙交酯)-b-聚乙二醇甲氧基(mpeg-b-PDLLA)来包裹DTX，得到了一个小尺寸的聚合物胶束(SPM)，同时我们用TAT多肽(TAT-PM)对SPM进行了表面功能化，以获得更高的渗透性。SPM和TAT-PM的直径均在15~26 nm之间。体外实验表明，TAT-PM对Capan-2 Luc PDAC细胞的生长抑制作用比SPM和多帕非更有效，并能诱导更多的细胞凋亡。在CAPAN-2Luc原位移植模型上，比较了SPM和TAT-PM与游离DTX的体内治疗效果。SPM的疗效优于游离DTX，而TAT-PM的疗效并不优于SPM。总体而言，这些结果揭示了SPM可以代表一种新的治疗胰腺癌的方法，但它对PDAC的通透性并不是唯一的决定因素。
Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance, and the small-sized nanocarrier loaded with platinum has been adopted to address this problem which is not suitable for loading docetaxel (DTX). In the present study, we used the poly(d,l-lactide)-b-polyethylene glycol-methoxy (mPEG-b-PDLLA) to encapsulate DTX and got a small-sized polymeric micelle (SPM); meanwhile we functionalized the SPM’s surface with TAT peptide (TAT-PM) for a higher permeability. The diameters of both SPM and TAT-PM were in the range of 15–26 nm. In vitro experiments demonstrated that TAT-PM inhibited Capan-2 Luc PDAC cells growth more efficiently and induced more apoptosis compared to SPM and Duopafei. The in vivo therapeutic efficiencies of SPM and TAT-PM compared to free DTX was investigated on the orthotopic transplantation model of Capan-2 Luc. SPM exerted better therapeutic efficiency than free DTX, however, TAT-PM didn’t outperformed SPM. Overall, these results disclosed that SPM could represent a new therapeutic approach against pancreatic cancer, but its permeability to PDAC was not the only decisive factor.
登录
查看更多内容
影响因子：
4.7
作者：
Iovanna J;Mallmann MC;Gonçalves A;Turrini O;Dagorn JC
通讯作者：
Dagorn JC
影响因子：
1.7
作者：
Li, Yunfei;Yang, Feifei;Gao, Zhonggao
通讯作者：
Gao, Zhonggao
影响因子：
11.2
作者：
Shimamura, Takeshi;Royal, Richard E.;Puri, Raj K.
通讯作者：
Puri, Raj K.
影响因子：
10.8
作者：
Nasongkla, Norased;Bey, Erik;Gao, Jinming
通讯作者：
Gao, Jinming
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A