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用中性粒细胞细胞膜包覆自组装纳米结构体可实现三阴性乳腺癌治疗的高特异性。

Coating a Self-Assembly Nanoconstruct with a Neutrophil Cell Membrane Enables High Specificity for Triple Negative Breast Cancer Treatment.

作者信息

Chowdhury Pallabita, Bhusetty Nagesh Prashanth Kumar, Hollingsworth T J, Jaggi Meena, Chauhan Subhash Chand, Yallapu Murali Mohan

机构信息

Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.

Laboratory of Signal Transduction, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States.

出版信息

ACS Appl Bio Mater. 2022 Aug 17. doi: 10.1021/acsabm.2c00614.

DOI:10.1021/acsabm.2c00614
PMID:35976626
Abstract

Breast cancer is one of the most commonly diagnosed cancers in American women. Triple negative breast cancer is among the most advanced and aggressive forms of breast cancer. Treatment options are limited for such cancers, making chemotherapy a convenient and effective treatment. Although these therapies can reduce morbidity and mortality, it is often followed by systemic side effects or relapse. Nanoparticles (NPs) have been considered for drug delivery approaches due to their ability to target various disease sites. Herein, we aim to develop a biomimetic NP construct (cell membrane-cloaked NPs) that exhibits specific affinity with triple negative breast cancer cells. In this regard, we designed biomimetic supramolecular nanoconstructs composed of a poly(vinyl pyrrolidone)-tannic acid (PVP-TA NPs/ PVT NPs) core and biofunctionalized with neutrophil cell membranes (PVT-NEU NPs). In this study, we have synthesized a PVT-NEU NP construct, characterized it, and evaluated it for improved targeting and therapeutic benefits in and models. Analysis of PVT-NEU NPs confirms the presence of the core of PVP-TA NPs coated with activated human neutrophil membranes. The study results confirmed that PVT-NEU NPs demonstrated an enhanced interaction and targeting with the tumor cells, thus improving the therapeutic activity of a model therapeutic agent (paclitaxel). Altogether, this study suggests the potential of biomimetic NPs as a promising therapeutic option for targeted drug delivery for advanced-stage breast cancer and other similar diseased conditions.

摘要

乳腺癌是美国女性中最常被诊断出的癌症之一。三阴性乳腺癌是乳腺癌中最晚期且侵袭性最强的类型之一。这类癌症的治疗选择有限,使得化疗成为一种便捷有效的治疗方法。尽管这些疗法可以降低发病率和死亡率,但往往会伴随着全身性副作用或复发。由于纳米颗粒(NPs)能够靶向各种疾病部位,因此已被考虑用于药物递送方法。在此,我们旨在开发一种与三阴性乳腺癌细胞具有特异性亲和力的仿生NP构建体(细胞膜包覆的NP)。在这方面,我们设计了由聚(乙烯基吡咯烷酮)-单宁酸(PVP-TA NPs / PVT NPs)核心组成并经中性粒细胞膜生物功能化的仿生超分子纳米构建体(PVT-NEU NPs)。在本研究中,我们合成了一种PVT-NEU NP构建体,对其进行了表征,并在[具体模型1]和[具体模型2]模型中评估了其改善的靶向性和治疗益处。对PVT-NEU NPs的分析证实了存在涂有活化人中性粒细胞膜的PVP-TA NPs核心。研究结果证实,PVT-NEU NPs与肿瘤细胞表现出增强的相互作用和靶向性,从而提高了模型治疗剂(紫杉醇)的治疗活性。总之,本研究表明仿生NP作为晚期乳腺癌和其他类似疾病状况的靶向药物递送的一种有前景的治疗选择具有潜力。

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