Safe and Targeted Sonodynamic Cancer Therapy Using Biocompatible Exosome-Based Nanosonosensitizers
Safe and Targeted Sonodynamic Cancer Therapy Using Biocompatible Exosome-Based Nanosonosensitizers
复制标题
DOI：
10.1021/acsami.0c22883
复制
发表时间：
2021-05-25
影响因子：
9.5
通讯作者：
Shim, Min Suk
中科院分区：
文献类型：
--
作者：
Cao, Thuy Giang Nguyen;Kang, Ji Hee;Shim, Min Suk
声动力疗法（SDT），其中用超声（US）照射的声敏剂产生细胞毒性活性氧物质（ROS），由于显著增加的组织穿透深度而作为光动力疗法的有希望的替代方案获得了极大的关注。开发能够选择性地将声敏剂存款到肿瘤组织中而没有全身毒性的纳米载体对于促进SDT向临床应用的转化至关重要。在这项研究中，外泌体，一类天然存在的纳米颗粒，被用作纳米载体的安全和癌症靶向交付的声敏剂，吲哚菁绿色（ICG）。外泌体用活性癌症靶向配体叶酸（FA）进行表面工程化，以增加ICG负载的外泌体（ExoICG）的癌症特异性。FA缀合的、负载ICG的外泌体（FA-ExoICG）极大地改善了ICG的水稳定性和细胞摄取，导致乳腺癌细胞中ROS产生显著增加。结果，FA-ExoICG显示出比ExoICG和游离ICG更大的针对癌细胞的声毒性。体内研究表明，与ExoICG相比，FA-ExoICG在肿瘤中积累更多，并且其药代动力学性质更上级。值得注意的是，通过单次静脉内注射FA-ExoICG和随后的US照射，小鼠中的肿瘤生长被显著抑制，而没有全身毒性。因此，这项研究表明，活性癌症靶向FA-ExoICG可以作为安全和靶向癌症治疗的有效纳米增敏剂。
Sonodynamic therapy (SDT), wherein sonosensitizers irradiated with ultrasound (US) produce cytotoxic reactive oxygen species (ROS), has garnered great attention as a promising alternative to photodynamic therapy owing to the significantly increased depth of tissue penetration. The development of nanocarriers that can selectively deposit sonosensitizers into tumor tissues without systemic toxicity is crucial to facilitate the translation of SDT to clinical use. In this study, exosomes, a class of naturally occurring nanoparticles, were utilized as nanocarriers for safe and cancer-targeted delivery of a sonosensitizer, indocyanine green (ICG). The exosomes were surface-engineered with an active cancer-targeting ligand, folic acid (FA), to increase the cancer specificity of the ICG-loaded exosomes (ExoICG). The FA-conjugated, ICG-loaded exosomes (FA-ExoICG) greatly improved aqueous stability and cellular uptake of ICG, resulting in significantly increased ROS generation in breast cancer cells. As a result, the FA-ExoICG demonstrated greater sonotoxicity against cancer cells than ExoICG and free ICG. The in vivo study revealed that compared to ExoICG, more FA-ExoICG accumulated in tumors, and their pharmacokinetic properties were superior. Notably, tumor growth in mice was significantly suppressed, without systemic toxicity, by a single intravenous injection of the FA-ExoICG and subsequent US irradiation. Therefore, this study demonstrated that active cancer-targeted FA-ExoICG could serve as effective nanosonosensitizers for safe and targeted cancer treatment.