Yang Ruihao, Hou Mengmeng, Gao Ya, Lu Shiyu, Zhang Lei, Xu Zhigang, Li Chang Ming, Kang Yuejun, Xue Peng
Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, School of Materials and Energy, Southwest University, Chongqing 400715, China.
Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing 400715, China.
Theranostics. 2019 Aug 14;9(21):6314-6333. doi: 10.7150/thno.36252. eCollection 2019.
Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. : As a proof-of-concept study, a multifunctional SF@MnO nanoparticle-based platform was strategically synthesized using SF as a reductant and a template a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO/ICG/DOX (SMID) nanocomplex. : The obtained product was highly reactive with endogenous hydrogen peroxide (HO) in tumor microenvironment, which was decomposed into O to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO and stably conjugated ICG The concurrent NIR fluorescence and magnetic resonance (MR) imaging both indicated effective tumor-specific enrichment of SMID nanoparticles enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. : This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.
再生丝素蛋白（SF）是一种具有出色生物相容性和生物降解性的天然生物大分子。然而，基于刺激响应性SF的纳米复合物在肿瘤诊断和治疗中的应用鲜有报道。作为一项概念验证研究，我们以SF作为还原剂和模板，通过一种极为简便的受生物矿化启发的结晶过程，策略性地合成了一种基于多功能SF@MnO纳米颗粒的平台。由于其介孔结构以及丰富的氨基和羧基末端残基，SF@MnO纳米颗粒共负载了光动力剂吲哚菁绿（ICG）和化疗药物阿霉素（DOX），形成了SF@MnO/ICG/DOX（SMID）纳米复合物。所获得的产物与肿瘤微环境中的内源性过氧化氢（HO）具有高反应性，HO分解为O以增强肿瘤特异性光动力疗法（PDT）。此外，由于SF@MnO独特的光热响应以及与ICG的稳定共轭，SMID纳米复合物在近红外（NIR）照射下产生强烈且稳定的光热效应用于光热疗法（PTT）。同时，近红外荧光和磁共振（MR）成像均表明SMID纳米颗粒在肿瘤中有效特异性富集，即增强渗透和滞留（EPR）效应。动物研究进一步证实，SMID纳米颗粒通过联合PTT/PDT/化疗显著提高了肿瘤抑制效果，且全身毒性或不良反应最小。这项研究证明了基于SF的纳米材料在解决由于肿瘤微环境不利于药物递送而导致的癌症治疗中的一些关键挑战方面具有广阔的潜力。
