Spherical polymeric nanoconstructs for combined chemotherapeutic and anti-inflammatory therapies
Spherical polymeric nanoconstructs for combined chemotherapeutic and anti-inflammatory therapies
复制标题
DOI：
10.1016/j.nano.2016.05.012
复制
发表时间：
2016-10-01
影响因子：
5.4
通讯作者：
Decuzzi, Paolo
中科院分区：
文献类型：
--
作者：
Lee, Aeju;Di Mascolo, Daniele;Decuzzi, Paolo
Nanoparticles can simultaneously deliver multiple agents to cancerous lesions enabling de facto combination therapies. Here, spherical polymeric nanoconstructs ( SPNs) are loaded with anti-cancer -docetaxel ( DTXL) - and anti-inflammatory - diclofenac ( DICL) molecules. In vitro, combination SPNs kill U87-MG cells twice as efficiently as DTXL SPNs, achieving a IC50 of 90.5 nM at 72 h. Isobologram analysis confirms a significant synergy ( CI = 0.56) between DTXL and DICL. In mice bearing non-orthotopic glioblastoma multiforme tumors, combination SPNs demonstrate higher inhibition in disease progression. At 70 days post treatment, the survival rate of mice treated with combination SPNs is of about 70%, against a 40% for DTXL SPNs and 0% for free DTXL. Combination SPNs dramatically inhibit COX-2 expression, modulating the local inflammatory status, and increase Caspase-3 expression, which is directly related to cell death. These results suggest that the combination of anti-cancer and anti-inflammatory molecules constitutes a potent strategy for inhibiting tumor growth. (C) 2016 Elsevier Inc. All rights reserved.
