An intelligent ZIF-8-gated polydopamine nanoplatform for in vivo cooperatively enhanced combination phototherapy.,Chemical Science

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An intelligent ZIF-8-gated polydopamine nanoplatform for in vivo cooperatively enhanced combination phototherapy.
Chemical Science ( IF 7.6 ) Pub Date : 2020-01-10 , DOI: 10.1039/c9sc06337d
Jie Feng _{1,

2} , Wenqian Yu ₁ , Zhen Xu ₁ , Fuan Wang ₁

Affiliation

The extreme complexity and heterogeneity of fatal tumors requires the development of combination phototherapy considering the limited therapeutic efficiency of conventional monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). However, tumor-specific drug administration and the accompanying hypoxia-restrained PDT present the main obstacles for executing an efficient combination phototherapy. Developing a highly biocompatible, tumor-specific, near infrared absorbing, and oxygen (O2)-evolving multifunctional nanoplatform is thus crucial for an effective PDT-based combination therapy. In this contribution, a multifunctional ZIF-8-gated polydopamine nanoparticle (PDA) carrier was synthesized for simultaneously delivering a photosensitizer and a catalase (CAT) into tumor cells, thus realizing a cooperatively enhanced combination photodynamic and photothermal therapy, as systematically demonstrated in vitro and in vivo. The ZIF-8 gatekeeper facilitates the simultaneous and effective delivery of these functional payloads, and the subsequent tumor acidic pH-stimulated drug release. This leads to a significant improvement of combination efficacy by ameliorating tumor hypoxic conditions since the CAT-mediated self-sufficient O2 generation could substantially promote an efficient PDT operation. In addition, this nanoplatform can effectively convert near infrared photoradiation into heat, resulting in thermally induced elimination of cancerous cells. As an intelligent multi-mode therapeutic nanosystem, this inorganic/organic hybrid nanosystem showed great potential for accurate cancer diagnosis and immediate therapy.

中文翻译：

一种用于体内协同增强组合光疗的智能 ZIF-8 门控聚多巴胺纳米平台。

考虑到传统单峰光动力疗法 (PDT) 或光热疗法 (PTT) 的有限治疗效率，致命肿瘤的极端复杂性和异质性需要开发联合光疗法。然而，肿瘤特异性药物给药和伴随的低氧抑制 PDT 是执行有效组合光疗的主要障碍。因此，开发一种高度生物相容性、肿瘤特异性、近红外吸收和氧气 (O2) 演变的多功能纳米平台对于有效的基于 PDT 的联合治疗至关重要。在这项贡献中，合成了一种多功能 ZIF-8 门控聚多巴胺纳米颗粒 (PDA) 载体，用于同时将光敏剂和过氧化氢酶 (CAT) 递送到肿瘤细胞中，从而实现协同增强的组合光动力和光热疗法，如体外和体内系统地证明的那样。ZIF-8 看门人促进了这些功能性有效载荷的同时有效传递，以及随后的肿瘤酸性 pH 刺激药物释放。由于 CAT 介导的自给自足 O2 生成可以显着促进有效的 PDT 操作，因此通过改善肿瘤缺氧条件导致联合疗效显着提高。此外，这种纳米平台可以有效地将近红外光辐射转化为热量，从而通过热诱导消除癌细胞。作为一种智能的多模式治疗纳米系统，这种无机/有机混合纳米系统在癌症的准确诊断和即时治疗方面显示出巨大的潜力。

更新日期：2020-02-13

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