Yin Ting, Chen Huaqing, Ma Aiqing, Pan Hong, Chen Ze, Tang Xiaofan, Huang Guojun, Liao Jianhong, Zhang Baozhen, Zheng Mingbin, Cai Lintao
Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Key Laboratory for Nanomedicine, Guangdong Medical University, Dongguan, 523808, PR China.
Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Biomaterials. 2023 Feb;293:121992. doi: 10.1016/j.biomaterials.2022.121992. Epub 2022 Dec 29.
Sonodynamic therapy (SDT), a combination of low-intensity ultrasound with a sonosensitizer, has been explored as a promising alternative for cancer therapy. However, condensed extracellular matrix (ECM) resulting in poor perfusion and extreme hypoxia in solid tumor potentially compromises effective SDT. Herein, we develop a novel cleavable collagenase-assistant and O-supplied nanosonosensitizer (FePO@HC), which is embedded through fusing collagenase (CLG) and human serum albumin (HSA), followed by encapsulating Ferric protoporphyrin (FeP) and dioxygen. As a smart carrier, HSA is stimuli-responsive and collapsed by reduced glutathione (GSH) overexpressed in tumor, resulting to the release of the components in FePO@HC. The released CLG acting as an artificial scissor, degrades the collagen fibers in tumor, thus, breaking tumor tissue and enhancing FePO accumulation in tumor inner with higher than that without CLG. Simultaneously, oxygen molecules are released from FePO in hypoxic environment and alleviate the tumor hypoxia. As a sonosensitizer, FeP is subsequently irradiated by ultrosound wave (US) and activates surrounding dioxygen to generate amount of singlet oxygen (O). Contributed from the ECM-degradation, such SDT-based nanosystem with increased sonosensitizer permeability and oxygen content highly improved the tumor inhibition efficacy without toxic effects. This study presents a new paradigm for ECM depletion-based strategy of deep-seated penetration, and will expand the nanomedicine application of metalloporphyrin sonosensitizers in SDT.
声动力疗法（SDT）是一种将低强度超声与声敏剂相结合的疗法，已被探索作为一种有前景的癌症治疗替代方法。然而，实体瘤中细胞外基质（ECM）浓缩导致灌注不良和极度缺氧，这可能会影响SDT的有效性。在此，我们开发了一种新型的可裂解胶原酶辅助且供氧的纳米声敏剂（FePO@HC），它通过将胶原酶（CLG）与人血清白蛋白（HSA）融合嵌入，随后包裹原卟啉铁（FeP）和氧气。作为一种智能载体，HSA具有刺激响应性，会被肿瘤中过表达的谷胱甘肽（GSH）破坏，从而导致FePO@HC中的成分释放。释放出的CLG作为一把人工剪刀，降解肿瘤中的胶原纤维，进而破坏肿瘤组织并增强FePO在肿瘤内部的蓄积，其蓄积量高于没有CLG时的情况。同时，氧分子在缺氧环境中从FePO释放出来，缓解肿瘤缺氧。作为声敏剂，FeP随后被超声波（US）照射并激活周围的氧气以产生大量单线态氧（O）。得益于ECM的降解，这种基于SDT的纳米系统具有更高的声敏剂渗透性和氧含量，极大地提高了肿瘤抑制效果且无毒性作用。本研究提出了一种基于ECM消耗的深层渗透策略的新范例，并将扩大金属卟啉声敏剂在SDT中的纳米医学应用。
