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基于顺铂交联的射频响应黑磷纳米凝胶用于多模式肿瘤协同治疗的精准化研究。

Radiofrequency-responsive black phosphorus nanogel crosslinked with cisplatin for precise synergy in multi-modal tumor therapies.

机构信息

National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, PR China.

Hubei Province Key Laboratory of Molecular Imaging, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

J Control Release. 2024 Sep;373:853-866. doi: 10.1016/j.jconrel.2024.07.075. Epub 2024 Aug 3.

Abstract

Radiofrequency-responsive nanoparticles (RFNPs) have drawn increasingly attentions as RF energy absorbing antenna to enhance antitumor efficacy of radiofrequency ablation (RFA). However, it remains a huge challenge for inorganic RFNPs to precisely synergize RFA with other antitumor modes in a clinically acceptable way on bio-safety and bio-compatibility. In this work, RF-responsive black phosphorus (BP) nanogel (BP-Pt@PNA) was successfully fabricated by crosslinking coordination of cisplatin with BP and temperature sensitive polymer PNA. BP-Pt@PNA exhibited strong RF-heating effect and RF-induced pulsatile release of cisplatin. Under RF irradiation, BP-Pt@PNA exhibited cytotoxic enhancement on 4T1 cells. By the synergistic effect of BP and cisplatin, BP-Pt@PNA achieved RF-stimulated systemic immune effect, thus induced enhance suppression on tumor growth and metastasis. Moreover, BP-Pt@PNA realized long-term drug retention in tumor and favorable embolization to tumor-feeding arteries. With high drug loading capacity and favorable bio-safety and bio-degradability, BP-Pt@PNA is expected as an ideal RFNP for precisely synergizing RFA with other antitumor modes in clinical application.

摘要

射频响应性纳米颗粒 (RFNPs) 作为射频能量吸收天线,可增强射频消融 (RFA) 的抗肿瘤疗效,因此受到越来越多的关注。然而,对于无机 RFNPs 来说,如何在生物安全性和生物相容性方面以临床可接受的方式精确地与其他抗肿瘤模式协同作用,仍然是一个巨大的挑战。在这项工作中,通过顺铂与 BP 的交联配位和温度敏感聚合物 PNA 的交联,成功制备了射频响应性黑磷 (BP) 纳米凝胶 (BP-Pt@PNA)。BP-Pt@PNA 表现出很强的射频加热效应和射频诱导的顺铂脉冲释放。在射频照射下,BP-Pt@PNA 对 4T1 细胞表现出增强的细胞毒性。通过 BP 和顺铂的协同作用,BP-Pt@PNA 实现了射频刺激的全身免疫效应,从而诱导增强对肿瘤生长和转移的抑制作用。此外,BP-Pt@PNA 实现了在肿瘤中的长期药物保留和对肿瘤供养动脉的有利栓塞。BP-Pt@PNA 具有高载药能力和良好的生物安全性和生物降解性,有望成为一种理想的 RFNP,可在临床应用中精确地与其他抗肿瘤模式协同作用。

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