In Vitro and In Vivo Effect of pH-Sensitive PLGA-TPGS-Based Hybrid Nanoparticles Loaded with Doxorubicin for Breast Cancer Therapy.
In Vitro and In Vivo Effect of pH-Sensitive PLGA-TPGS-Based Hybrid Nanoparticles Loaded with Doxorubicin for Breast Cancer Therapy.
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DOI：
10.3390/pharmaceutics14112394
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发表时间：
2022-11-06
期刊：
影响因子：
5.4
通讯作者：
Barros ALB
中科院分区：
文献类型：
--
作者：
Fernandes RS;Arribada RG;Silva JO;Silva-Cunha A;Townsend DM;Ferreira LAM;Barros ALB
多柔比星（DOX）是临床上用于治疗乳腺癌患者的化疗剂。尽管其有效性，其固有的不良毒副作用往往限制其临床应用。为了克服这些缺点，脂质-聚合物杂化纳米颗粒（LPNP）作为有前途的纳米平台而出现，其将脂质体和聚合物纳米颗粒两者的优点联合收割机结合到单个递送系统中。α-生育酚琥珀酸酯（TS）是维生素E的衍生物，显示出有效的抗癌机制，并且它是一种有趣的佐剂方法。在本研究中，我们设计了一种pH敏感的PLGA-聚合物-核/TPGS-lipid-shell杂化纳米粒，负载DOX和TS（LPNP_TS-DOX）。纳米粒子的物理化学和形态特征。在4 T1、MCF-7和MDA-MB-231细胞系中进行了细胞毒性研究、迁移试验和细胞摄取。在4 T1乳腺肿瘤荷瘤小鼠中评价体内抗肿瘤活性。体外研究显示，与游离DOX相比，4 T1细胞系的细胞活力、细胞迁移和细胞摄取显著降低。体内抗肿瘤活性显示LPNP-TS-DOX在控制肿瘤生长方面比其他治疗更有效。DOX的高细胞内化和pH触发的有效负载释放导致药物在肿瘤区域的积累增加，沿着与TS的协同组合，最终产生更大的抗肿瘤功效。这些数据支持LPNP-TS-DOX作为用于乳腺癌治疗的有前景的药物递送系统。
Doxorubicin (DOX) is an antineoplastic agent clinically employed for treating breast cancer patients. Despite its effectiveness, its inherent adverse toxic side effects often limit its clinical application. To overcome these drawbacks, lipid–polymer hybrid nanoparticles (LPNP) arise as promising nanoplatforms that combine the advantages of both liposomes and polymeric nanoparticles into a single delivery system. Alpha-tocopherol succinate (TS) is a derivative of vitamin E that shows potent anticancer mechanisms, and it is an interesting approach as adjuvant. In this study, we designed a pH-sensitive PLGA-polymer-core/TPGS-lipid-shell hybrid nanoparticle, loaded with DOX and TS (LPNP_TS-DOX). Nanoparticles were physicochemically and morphologically characterized. Cytotoxicity studies, migration assay, and cellular uptake were performed in 4T1, MCF-7, and MDA-MB-231 cell lines. Antitumor activity in vivo was evaluated in 4T1 breast tumor-bearing mice. In vitro studies showed a significant reduction in cell viability, cell migration, and an increase in cellular uptake for the 4T1 cell line compared to free DOX. In vivo antitumor activity showed that LPNP-TS-DOX was more effective in controlling tumor growth than other treatments. The high cellular internalization and the pH-triggered payload release of DOX lead to the increased accumulation of the drugs in the tumor area, along with the synergic combination with TS, culminating in greater antitumor efficacy. These data support LPNP-TS-DOX as a promising drug delivery system for breast cancer treatment.
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影响因子：
--
作者：
Bayat Mokhtari R;Homayouni TS;Baluch N;Morgatskaya E;Kumar S;Das B;Yeger H
通讯作者：
Yeger H
影响因子：
5
作者：
Makadia HK;Siegel SJ
通讯作者：
Siegel SJ
影响因子：
16.1
作者：
Li, Yinghuan;Wang, Jie;Wientjes, M. Guillaume;Au, Jessie L. -S.
通讯作者：
Au, Jessie L. -S.
影响因子：
12.8
作者：
Lim, Soo-Jeong;Choi, Moon Kyung;Kim, Joo Kyoung
通讯作者：
Kim, Joo Kyoung
DOI：
10.1111/j.1365-2613.2007.00539.x
发表时间：
2007-10-01
影响因子：
3
作者：
DuPre, Sally A.;Redelman, Doug;Hunter, Kenneth W., Jr.
通讯作者：
Hunter, Kenneth W., Jr.