Dual Receptor-Targeted Theranostic Nanoparticles for Localized Delivery and Activation of Photodynamic Therapy Drug in Glioblastomas.
Dual Receptor-Targeted Theranostic Nanoparticles for Localized Delivery and Activation of Photodynamic Therapy Drug in Glioblastomas.
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DOI：
10.1021/acs.molpharmaceut.5b00216
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发表时间：
2015-09-08
影响因子：
4.9
通讯作者：
Broome AM
中科院分区：
文献类型：
--
作者：
Dixit S;Miller K;Zhu Y;McKinnon E;Novak T;Kenney ME;Broome AM
已经提出用两种或更多种受体结合肽靶向金纳米颗粒（AuNP）来解决过表达多种细胞表面受体的胶质母细胞瘤的瘤内异质性，以最终提高治疗功效。金纳米粒子共轭肽对表皮生长因子和转铁蛋白受体和光敏剂酞菁4（Pc 4）装载已被设计和比较单靶向金纳米粒子在体外和体内研究。与仅过表达一种细胞表面受体的细胞相比，具有约41 nm粒径的（EGFpep+Tfpep）-AuNPs-Pc 4改善了特异性，并协同作用以减少过表达两种细胞表面受体的人胶质瘤细胞中的最大积累时间。实现了增强的细胞结合和增加的细胞毒性。体内研究表明，这些药物在脑肿瘤区域有显著的蓄积。
Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed to address intratumoral heterogeneity of glioblastomas that overexpress multiple cell surface receptors to ultimately improve therapeutic efficacy. AuNPs conjugated with peptides against both the epidermal growth factor and transferrin receptors and loaded with the photosensitizer phthalocyanine 4 (Pc 4) have been designed and compared with monotargeted AuNPs for in vitro and in vivo studies. The (EGFpep+Tfpep)-AuNPs-Pc 4 with a particle size of ~41 nm improved both specificity and worked synergistically to decrease time of maximal accumulation in human glioma cells that overexpressed two cell surface receptors as compared to cells that overexpressed only one. Enhanced cellular association and increased cytotoxicity were achieved. In vivo studies show notable accumulation of these agents in the brain tumor regions.