“冰火”超分子细胞结合药物传递平台用于深层肿瘤消融和增强抗肿瘤免疫。
"Ice & Fire" Supramolecular Cell-Conjugation Drug Delivery Platform for Deep Tumor Ablation and Boosted Anti-Tumor Immunity.
发表日期:2023 Aug 07
作者:
Meng Xu, Haidong Zha, Jiamao Chen, Simon Ming-Yuen Lee, Qi Wang, Ruibing Wang, Ying Zheng
来源:
Immunity & Ageing
摘要:
目前的临床治疗中,癌症复发和转移是两个主要的挑战。在此,我们合成了一种新型的基于双酮吡咯吡咯 (DCN) 的光热试剂,具有独特的 J-聚集诱导红移效应,在安全功率下(0.33 W/cm2 )实现了高效的肿瘤热消融。同时,近红外吸收的 DCN 和亲水性聚合物中共载入了亚硝基乙酰青霉胺 (SNAP),以实现热诱导的大量释放一氧化氮(NO),NO 可以形成氧化剂过氧亚硝酸根(ONOO-),活化基质金属蛋白酶(MMPs),从而降解紧密的肿瘤细胞外基质(ECM),改善消融深度和免疫细胞的浸润。通过一种简便的超分子组装方法,DCN/SNAP 纳米颗粒锚定在液氮冷冻的癌细胞(LNF)上,在仅经过一次治疗后实现了增强的抗肿瘤免疫反应,并有效抑制了远处肿瘤和肺转移。2D/3D 细胞实验和双侧肿瘤模型验证了这种超分子细胞结合平台的安全性和有效性,证实了热消融-气体渗透-抗原呈递治疗模式具有良好的抗癌前景。本文受版权保护,版权所有。
Cancer recurrence and metastasis are two major challenges in the current clinical therapy. Here, we synthesized a novel diketopyrrolopyrrole-based photothermal reagent (DCN) with unique J-aggregation-induced redshift to achieve efficient tumor thermal ablation under safe power (0.33 W/cm2 ). Meanwhile, S-nitroso-N-acetylpenicillamine (SNAP) was co-loaded with near-infrared (NIR)-absorbing DCN in amphiphilic polymers to realize heat-induced massive release of nitric oxide (NO), which could form oxidant peroxynitrite (ONOO- ) to active MMPs, thereby degrading the compact tumor extracellular matrix (ECM) to improve the ablation depth and infiltration of immune cells. Through a facile supramolecular assembly method, the DCN/SNAP nanoparticles were anchored to liquid nitrogen-frozen cancer cells (LNF), achieving enhanced anti-tumor immune responses and effective inhibition of distant tumor and pulmonary metastases after only one treatment. The safety and effectiveness of this supramolecular cell-conjugation platform were verified by 2D/3D cellular experiments and bilateral tumor model, confirming the thermal ablation-gas permeation-antigen presentation therapeutic mode had promising anticancer prospects. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.