EGFR-mediated intracellular delivery of Pc 4 nanoformulation for targeted photodynamic therapy of cancer: in vitro studies.
EGFR-mediated intracellular delivery of Pc 4 nanoformulation for targeted photodynamic therapy of cancer: in vitro studies.
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DOI：
10.1016/j.nano.2011.09.012
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发表时间：
2012-07
影响因子：
5.4
通讯作者：
Sen Gupta, Anirban
中科院分区：
文献类型：
--
作者：
Master, Alyssa M.;Qi, Yizhi;Oleinick, Nancy L.;Sen Gupta, Anirban
在光动力疗法（PDT）中，光敏剂的光激活会导致活性氧物质的产生，这些活性氧物质可引发多种细胞死亡机制。在癌细胞内利用这一过程能够实现微创且靶向性的癌症治疗。基于这一原理，在此我们展示了将一种高度疏水的光敏剂Pc 4装载于生物相容性的聚乙二醇 - 聚己内酯嵌段共聚物胶束中，并实现肿瘤靶向递送。这些胶束在表面用表皮生长因子受体（EGFR）靶向的GE11肽进行修饰，以便在体外对过表达EGFR的癌细胞进行主动靶向。将装载Pc 4且靶向EGFR的胶束与过表达EGFR的A431表皮样癌细胞在不同时间段进行孵育，通过落射荧光显微镜确定细胞对Pc 4的摄取情况。随后对这些细胞进行光照射，并通过MTT法和荧光活/死细胞检测法确定在不同孵育时间段内光动力疗法诱导的细胞死亡情况。我们的研究结果表明，对装载Pc 4的胶束进行主动的EGFR靶向可加速药物的细胞内摄取。因此，这在更短时间内增强了光动力疗法诱导的细胞毒性。
In photodynamic therapy (PDT), the light-activation of a photosensitizer leads to the generation of reactive oxygen species that can trigger various mechanisms of cell death. Harnessing this process within cancer cells enables minimally invasive yet targeted cancer treatment. With this rationale, here we demonstrate tumor-targeted delivery of a highly hydrophobic photosensitizer Pc 4 loaded within biocompatible PEG-PCL block-copolymer micelles. The micelles were surface-modified with EGFR-targeting GE11-peptides for active targeting of EGFR-overexpressing cancer cells, in vitro. Pc 4-loaded EGFR-targeted micelles were incubated with EGFR-overexpressing A431 epidermoid carcinoma cells for various time periods, to determine Pc 4 uptake by epifluorescence microscopy. The cells were subsequently photoirradiated and PDT-induced cell death for various incubation periods was determined by MTT assay and fluorescence Live/Dead assay. Our results indicate that active EGFR-targeting of the Pc 4-loaded micelles accelerates intracellular uptake of the drug. Consequently this enhances the PDT-induced cytotoxicity within shorter time periods.
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影响因子：
1.9
作者：
Rapidis, Alexander D.;Vermorken, Jan B.;Bourhis, Jean
通讯作者：
Bourhis, Jean
DOI：
10.1007/978-1-60761-609-2_26
发表时间：
2010-01-01
期刊：
CANCER NANOTECHNOLOGY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Gaitanis, Alexander;Staal, Stephen
通讯作者：
Staal, Stephen
影响因子：
4.8
作者：
Li, ZH;Zhao, RJ;Gu, JR
通讯作者：
Gu, JR
影响因子：
3.3
作者：
Allison, Ron R.;Downie, Gordon H.;Sibata, Claudio H.
通讯作者：
Sibata, Claudio H.
DOI：
10.1016/s1095-6433(01)00545-1
发表时间：
2002-05-01
影响因子：
2.3
作者：
Pogue, BW;O'Hara, JA;Swartz, H
通讯作者：
Swartz, H