Co-Administration Of iRGD Enhances Tumor-Targeted Delivery And Anti-Tumor Effects Of Paclitaxel-Loaded PLGA Nanoparticles For Colorectal Cancer Treatment
Co-Administration Of iRGD Enhances Tumor-Targeted Delivery And Anti-Tumor Effects Of Paclitaxel-Loaded PLGA Nanoparticles For Colorectal Cancer Treatment
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iRGD 的共同给药增强了负载紫杉醇的 PLGA 纳米颗粒的肿瘤靶向递送和抗肿瘤作用，用于结直肠癌治疗
DOI：
10.2147/ijn.s219820
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发表时间：
2019-11
影响因子：
8
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Zhong Y;Su T;Shi QX;Feng YN;Tao Z;Huang QX;Li L;Hu LQ;Li SF;Tan H;Liu S;Yang H
纳米颗粒在改善化疗药物的溶解度和组织特异性分布方面表现出巨大的潜力;然而，在肿瘤中观察到的被动和高度可变的增强渗透性和保留（EPR）效应经常导致纳米药物向肿瘤中的递送不足。肿瘤穿透肽iRGD可以通过与整合素结合并与组织穿透受体神经纤毛蛋白-1相互作用来主动增强纳米颗粒向肿瘤中的肿瘤选择性递送。材料与方法为了改善结直肠癌的治疗，在这项研究中，我们制备了紫杉醇（PTX）负载的PLGA纳米粒（PLGA-PTX），并通过与iRGD共同给药来评估其肿瘤靶向和抗肿瘤活性。结果与游离PTX相比，包封PTX保留了对各种结直肠癌细胞的优先细胞毒性，同时有效地保留了健康细胞。PLGA-PTX处理导致细胞周期停滞在G2/M期和细胞凋亡，从而抑制癌细胞的迁移和侵袭。PLGA-PTX与iRGD联合应用对细胞毒性的增强作用不明显。尽管如此，iRGD受体整联蛋白和神经纤毛蛋白-1被发现主要在携带结肠直肠肿瘤的小鼠中的丰富的肿瘤血管上过表达。因此，纳米颗粒与iRGD的共同施用促进了纳米颗粒在体内选择性递送到肿瘤组织中。此外，与每种单独试剂相比，联合方案增强了抗肿瘤作用。结论由于iRGD受体在肿瘤血管中过表达，PLGA纳米粒与iRGD肽的联合应用为促进活性药物在肿瘤中的蓄积提供了一种有前景的药物递送策略。这种缺乏共价缀合的共施用系统提供了将各种治疗剂与iRGD组合以实现个性化纳米治疗的更方便的手段。
Background Nanoparticles exhibit great promise for improving the solubility and tissue-specific distribution of chemotherapeutic agents; however, the passive and highly variable enhanced permeability and retention (EPR) effects observed in tumors frequently leads to insufficient delivery of nanodrugs into tumors. The tumor-penetrating peptide iRGD can actively enhance tumor-selective delivery of nanoparticles into tumors by binding to integrin and interacting with tissue-penetrating receptor neuropilin-1. Materials and methods To improve colorectal cancer treatment, in this study, we prepared a paclitaxel (PTX)-loaded PLGA nanoparticle (PLGA-PTX) and evaluated its tumor-targeting and antitumor activity by co-administration with iRGD. Results Compared to free PTX, encapsulated PTX retained preferential cytotoxicity toward various colorectal cancer cells while effectively sparing healthy cells. PLGA-PTX treatment resulted in cell cycle arrest at the G2/M phase and apoptosis, leading to inhibition of cancer cell migration and invasion. PLGA-PTX combined with iRGD displayed little enhancement of cytotoxicity in vitro. Despite this, iRGD receptors integrin and neuropilin-1 were found to be primarily overexpressed on abundant tumor vessels in mice bearing colorectal tumors. Consequently, co-administration of nanoparticles with iRGD promoted the selective delivery of nanoparticles into tumor tissues in vivo. Additionally, the combined regimen enhanced the antitumor effects compared to those of each individual reagent. Conclusion Our findings suggest that PLGA nanoparticles combined with the iRGD peptide provide a promising drug delivery strategy for facilitating active drug accumulation into tumors, given that iRGD receptors are overexpressed on tumor vessels. This co-administration system lacking covalent conjugation provides a more convenient means to combine various therapeutic agents with iRGD to achieve personalized nanotherapy.
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影响因子：
5
作者：
Hassan MS;Awasthi N;Li J;Williams F;Schwarz MA;Schwarz RE;von Holzen U
通讯作者：
von Holzen U
DOI：
10.1016/j.jconrel.2017.09.026
发表时间：
2017-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Wang F;Porter M;Konstantopoulos A;Zhang P;Cui H
通讯作者：
Cui H
影响因子：
17.1
作者：
G. Tietjen;W. Saltzman
通讯作者：
G. Tietjen;W. Saltzman
影响因子：
10.8
作者：
Majumder, Poulami;Bhunia, Sukanya;Chaudhuri, Arabinda
通讯作者：
Chaudhuri, Arabinda
纳米医学在治疗乳腺癌中的应用：当前的艺术状态。
影响因子：
8
作者：
Wu D;Si M;Xue HY;Wong HL
通讯作者：
Wong HL