Selective Uptake Into Drug Resistant Mammalian Cancer by Cell Penetrating Peptide-Mediated Delivery
Selective Uptake Into Drug Resistant Mammalian Cancer by Cell Penetrating Peptide-Mediated Delivery
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DOI：
10.1021/acs.bioconjchem.8b00429
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发表时间：
2018-10-01
影响因子：
4.7
通讯作者：
Strouse, Geoffrey F.
中科院分区：
文献类型：
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作者：
Carnevale, Kate J. F.;Muroski, Megan E.;Strouse, Geoffrey F.
过去十年的研究已经确定了癌症治疗应用中多药耐药（MDR）的几个关键限制特征，例如限制治疗吸收的细胞表面糖蛋白受体的演变，导致保护免受多药耐药介质的代谢变化，这些介质增强了治疗剂的降解或外排，以及难以确保内吞后保留完整和功能性药物。纳米颗粒已被证明是多种治疗剂的有效递送载体，并且在基于核酸的药剂的情况下，它们提供保护性优势。将细胞穿透肽（也称为蛋白质转导结构域）功能化到荧光量子点的表面上创建了标记的递送包，以研究MDR癌细胞中药物转运的细微差别和困难，以用于基于多种纳米颗粒的治疗递送策略的潜在未来临床应用。在这项研究中，使用了八种不同的细胞穿透肽，（CAAKA、HSV 1-VP 22、HIV-TAT、HIV-gp 41、Ku-70、hCT（9-32）、整合素-β 3和K-FGF），以检查癌症与耐药性黑色素瘤中的不同细胞摄取概况（A375和A375-R）、间皮瘤（MSTO和MST 0-R）和神经胶质瘤（大鼠9 L和9 L-R，以及人U87和LN 18）细胞系。本研究的结果表明，细胞穿透肽的摄取随耐药状态和细胞类型而变化，可能是由于细胞表面标志物的变化。这项研究为在耐药癌症模型中开发功能性纳米平台递送系统提供了见解。
Research over the past decade has identified several of the key limiting features of multidrug resistance (MDR) in cancer therapy applications, such as evolving glycoprotein receptors at the surface of the cell that limit therapeutic uptake, metabolic changes that lead to protection from multidrug resistant mediators which enhance degradation or efflux of therapeutics, and difficulty ensuring retention of intact and functional drugs once endocytosed. Nanoparticles have been demonstrated to be effective delivery vehicles for a plethora of therapeutic agents, and in the case of nucleic acid based agents, they provide protective advantages. Functionalizing cell penetrating peptides, also known as protein transduction domains, onto the surface of fluorescent quantum dots creates a labeled delivery package to investigate the nuances and difficulties of drug transport in MDR cancer cells for potential future clinical applications of diverse nanoparticle-based therapeutic delivery strategies. In this study, eight distinct cell penetrating peptides were used (CAAKA, HSV1-VP22, HIV-TAT, HIV-gp41, Ku-70, hCT(9-32), integrin-beta 3, and K-FGF) to examine the different cellular uptake profiles in cancer versus drug resistant melanoma (A375 & A375-R), mesothelioma (MSTO & MSTO-R), and glioma (rat 9L and 9L-R, and human U87 & LN18) cell lines. The results of this study demonstrate that cell penetrating peptide uptake varies with drug resistance status and cell type, likely due to changes in cell surface markers. This study provides insight into developing functional nanoplatform delivery systems in drug resistant cancer models.