基于 SDS 的新型多芯聚电解质纳米载体用于紫杉醇递送-合成、表征及对乳腺癌细胞的活性。

New SDS-Based Polyelectrolyte Multicore Nanocarriers for Paclitaxel Delivery-Synthesis, Characterization, and Activity against Breast Cancer Cells.

机构信息

Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 St, 90-236 Lodz, Poland.

Laboratory of Microscopic Imaging and Specialized Biological Techniques, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16 St, 90-237 Lodz, Poland.

出版信息

Cells. 2023 Aug 11;12(16):2052. doi: 10.3390/cells12162052.

DOI:10.3390/cells12162052

PMID:37626862

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10453607/

Abstract

The low distribution of hydrophobic anticancer drugs in patients is one of the biggest limitations during conventional chemotherapy. SDS-based polyelectrolyte multicore nanocarriers (NCs) prepared according to the layer by layer (LbL) procedure can release paclitaxel (PTX), and selectively kill cancer cells. Our main objective was to verify the antitumor properties of PTX-loaded NCs and to examine whether the drug encapsulated in these NCs retained its cytotoxic properties. The cytotoxicity of the prepared nanosystems was tested on MCF-7 and MDA-MB-231 tumour cells and the non-cancerous HMEC-1 cell line in vitro. Confocal microscopy, spectrophotometry, spectrofluorimetry, flow cytometry, and RT PCR techniques were used to define the typical hallmarks of apoptosis. It was demonstrated that PTX encapsulated in the tested NCs exhibited similar cytotoxicity to the free drug, especially in the triple negative breast cancer model. Moreover, SDS/PLL/PTX and SDS/PLL/PGA/PTX significantly reduced DNA synthesis. In addition, PTX-loaded NCs triggered apoptosis and upregulated the transcription of Bax, AIF, cytochrome-c, and caspase-3 mRNA. Our data demonstrate that these novel polyelectrolyte multicore NCs coated with PLL or PLL/PGA are good candidates for delivering PTX. Our discoveries have prominent implications for the possible choice of newly synthesized, SDS-based polyelectrolyte multicore NCs in different anticancer therapeutic applications.

摘要

疏水性抗癌药物在患者体内分布低是传统化疗的最大限制之一。根据层层（LbL）程序制备的基于 SDS 的聚电解质多核纳米载体（NCs）可以释放紫杉醇（PTX），并选择性地杀死癌细胞。我们的主要目标是验证载紫杉醇 NCs 的抗肿瘤特性，并研究这些 NCs 中封装的药物是否保留其细胞毒性。在体外，通过 MCF-7 和 MDA-MB-231 肿瘤细胞和非癌细胞 HMEC-1 细胞系测试了制备的纳米系统的细胞毒性。共聚焦显微镜、分光光度法、荧光分光光度法、流式细胞术和 RT-PCR 技术用于定义细胞凋亡的典型特征。结果表明，封装在测试 NCs 中的 PTX 表现出与游离药物相似的细胞毒性，尤其是在三阴性乳腺癌模型中。此外，SDS/PLL/PTX 和 SDS/PLL/PGA/PTX 显著降低了 DNA 合成。此外，载紫杉醇 NCs 触发了细胞凋亡，并上调了 Bax、AIF、细胞色素-c 和 caspase-3 mRNA 的转录。我们的数据表明，这些新型带 PLL 或 PLL/PGA 的聚电解质多核 NCs 是递送 PTX 的良好候选物。我们的发现对 SDS 基聚电解质多核 NCs 在不同抗癌治疗应用中的可能选择具有重要意义。