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采用合理设计的 PEG 化铂纳米粒提高阿霉素的递送,用于治疗黑色素瘤。

Improved delivery of doxorubicin using rationally designed PEGylated platinum nanoparticles for the treatment of melanoma.

机构信息

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, 500007, Telangana State, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, 500007, Telangana State, India.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Mar;108:110375. doi: 10.1016/j.msec.2019.110375. Epub 2019 Nov 5.


DOI:10.1016/j.msec.2019.110375
PMID:31924026
Abstract

Efficient delivery of chemotherapeutic drugs to tumor cells is one of the crucial issues for modern day cancer therapy. In this article, we report the synthesis of poly ethylene glycol (PEG) assisted colloidal platinum nanoparticles (PtNPs) by borohydride reduction method at room temperature. PtNPs are stable at room temperature for more than 2 years and are stable in serum and phosphate buffer (pH = 7.4) solution for one week. PtNPs show biocompatibility in different normal cell lines (in vitro) and chicken egg embryonic model (ex vivo). Further, we designed and fabricated PtNPs-based drug delivery systems (DDS: PtNPs-DOX) using doxorubicin (DOX), a FDA approved anticancer drug. Various analytical techniques were applied to characterize the nanomaterials (PtNPs) and DDS (PtNPs-DOX). This DDS exhibits inhibition of cancer cell (B16F10 and A549) proliferation, observed by different in vitro assays. PtNPs-DOX induces apoptosis in cancer cells observed by annexin-V staining method. Intraperitoneal (IP) administration of PtNPs-DOX shows substantial reduction of tumor growth in subcutaneous murine melanoma tumor model compared to control group with free drug. Up-regulation of tumor suppressor protein p53 and down regulation of SOX2 and Ki-67 proliferation markers in melanoma tumor tissues (as observed by immunofluorescence and western blot analysis) indicates probable molecular mechanism for the anticancer activity of DDS. Considering the in vitro and pre-clinical (in vivo) results in murine melanoma, it is believed that platinum nanoparticle-based drug delivery formulation could be exploited to develop an alternative therapeutic nanomedicine for cancer therapy in the near future.

摘要

高效地将化疗药物递送到肿瘤细胞是现代癌症治疗的关键问题之一。在本文中,我们报告了通过硼氢化钠还原法在室温下合成聚乙二醇(PEG)辅助胶体铂纳米粒子(PtNPs)。PtNPs 在室温下稳定超过 2 年,并且在血清和磷酸盐缓冲液(pH=7.4)溶液中稳定一周。PtNPs 在不同的正常细胞系(体外)和鸡胚模型(体外)中表现出生物相容性。此外,我们使用多柔比星(DOX)设计并制备了基于 PtNPs 的药物递送系统(DDS:PtNPs-DOX),DOX 是一种经过 FDA 批准的抗癌药物。采用各种分析技术对纳米材料(PtNPs)和 DDS(PtNPs-DOX)进行了表征。通过不同的体外实验观察到,这种 DDS 抑制了癌细胞(B16F10 和 A549)的增殖。通过 Annexin-V 染色法观察到 PtNPs-DOX 诱导癌细胞凋亡。与对照组(游离药物)相比,PtNPs-DOX 经腹腔(IP)给药后,在皮下鼠黑色素瘤肿瘤模型中显著减少了肿瘤生长。在黑色素瘤肿瘤组织中观察到肿瘤抑制蛋白 p53 的上调和 SOX2 和 Ki-67 增殖标志物的下调(通过免疫荧光和 Western blot 分析),表明 DDS 具有抗癌活性的可能分子机制。考虑到在体外和临床前(体内)实验结果,基于铂纳米粒子的药物递送制剂有望在不久的将来开发出一种用于癌症治疗的替代治疗性纳米医学。

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Int J Pharm X. 2025-7-5

[3]
Functionalized Nanomaterials in Cancer Treatment: A Review.

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[4]
A drug delivery system of siRNA nanoparticles loaded by mesenchymal stem cells on choroidal neovascularization.

Nanomedicine (Lond). 2024

[5]
Recent advances in nanomaterial-based drug delivery systems for melanoma therapy.

ADMET DMPK. 2023-10-24

[6]
Impact of Physical Exercise on Melanoma Hallmarks: Current Status of Preclinical and Clinical Research.

J Cancer. 2024-1-1

[7]
Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles.

ACS Omega. 2023-7-19

[8]
Functionalized Metal Nanoparticles in Cancer Therapy.

Pharmaceutics. 2023-7-11

[9]
The Effect of PEGylation on Drugs' Pharmacokinetic Parameters; from Absorption to Excretion.

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[10]
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