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用于近红外光触发药物释放及增强胃癌光热化疗协同作用的光热响应性诊疗纳米复合材料

Photothermally responsive theranostic nanocomposites for near-infrared light triggered drug release and enhanced synergism of photothermo-chemotherapy for gastric cancer.

作者信息

Zhou Taicheng, Wu Lili, Ma Ning, Tang Fuxin, Chen Jialin, Jiang Zhipeng, Li Yingru, Ma Tao, Yang Na, Zong Zhen

机构信息

Department of Gastroenterological Surgery and Hernia Center The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou Guangdong China.

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou Guangdong China.

出版信息

Bioeng Transl Med. 2022 Jul 12;8(1):e10368. doi: 10.1002/btm2.10368. eCollection 2023 Jan.

Abstract

Near-infrared (NIR) photothermal therapy plays a critical role in the cancer treatment and diagnosis as a promising carcinoma treatment modalities nowadays. However, development of clinical application has been greatly limited due to the inefficient drug release and low tumor accumulation. Herein, we designed a NIR-light triggered indocyanine green (ICG)-based PCL core/P(MEOMA--HMAM) shell nanocomposites (PPH@ICG) and evaluated their therapeutic effects in vitro and in vivo. The anticancer drug 5-fluorouracil (5Fu) and the photothermal agent ICG were loaded into a thermo-sensitive micelle (PPH@5Fu@ICG) by self-assembly. The nanoparticles formed were characterized using transmission electron microscopy, dynamic light scattering, and fluorescence spectra. The thermo-sensitive copolymer (PPH@5Fu@ICG) showed a great temperature-controlled drug release response with lower critical solution temperature. In vitro cellular uptake and TEM imaging proved that PPH@5Fu@ICG nanoparticles can home into the lysosomal compartments under NIR. Moreover, in gastric tumor-bearing nude mice, PPH@5Fu@ICG + NIR group exhibited excellent improvement in antitumor efficacy based on the NIR-triggered thermo-chemotherapy synergy, both in vitro and in vivo. In summary, the proposed strategy of synergistic photo-hyperthermia chemotherapy effectively reduced the 5Fu dose, toxic or side effect, which could serve as a secure and efficient approach for cancer theranostics.

摘要

近红外(NIR)光热疗法作为一种很有前景的癌症治疗方式,在癌症治疗和诊断中发挥着关键作用。然而,由于药物释放效率低下和肿瘤蓄积量低,其临床应用的发展受到了极大限制。在此,我们设计了一种基于近红外光触发的吲哚菁绿(ICG)的聚己内酯核/聚(甲基丙烯酸乙酯-共-甲基丙烯酸羟乙酯)壳纳米复合材料(PPH@ICG),并评估了它们在体外和体内的治疗效果。抗癌药物5-氟尿嘧啶(5Fu)和光热剂ICG通过自组装被载入热敏胶束(PPH@5Fu@ICG)中。使用透射电子显微镜、动态光散射和荧光光谱对形成的纳米颗粒进行了表征。热敏共聚物(PPH@5Fu@ICG)在较低临界溶液温度下表现出良好的温度控制药物释放响应。体外细胞摄取和透射电镜成像证明,PPH@5Fu@ICG纳米颗粒在近红外光下可归巢至溶酶体区室。此外,在荷胃癌裸鼠中,基于近红外触发的热化疗协同作用,PPH@5Fu@ICG + 近红外光组在体外和体内均表现出优异的抗肿瘤疗效改善。总之,所提出的光热疗协同化疗策略有效降低了5Fu剂量、毒性或副作用,可作为一种安全有效的癌症诊疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed37/9842049/8937d737f35e/BTM2-8-e10368-g001.jpg

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