用于蛋白质药物封装和细胞内递送的单宁酸辅助生物矿化策略,ACS Applied Materials & Interfaces

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用于蛋白质药物封装和细胞内递送的单宁酸辅助生物矿化策略
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-11-02 , DOI: 10.1021/acsami.2c15205
Sheng-Yan Yin ₁ , Yingcai Hu ₁ , Jing Zheng ₁ , Jishan Li ₁ , Ronghua Yang ₁

Affiliation

蛋白质疗法一直被认为是调节细胞功能和治疗肿瘤最直接、最安全的方法之一。然而，蛋白质药物安全有效的细胞内递送仍然是一个关键挑战。在此，我们开发了一种单宁酸辅助的生物矿化策略，用于蛋白质药物的包封和细胞内递送。选择核糖核酸酶A和葡萄糖氧化酶（GOD）作为蛋白药物模型。RNase A、GOD、TA和Mn ²⁺一锅混合得到RG@MT，随后进行CaCO _{3包被，通过生物矿化构建RG@MT@C。}一旦RG@MT@C被内吞，溶酶体的酸性环境会溶解CaCO ₃的保护层并产生大量的CO ₂引起溶酶体破裂，确保 RG@MT@C 的溶酶体逃逸，从而将生成的 TA-Mn ²⁺、RNase A 和 GOD 释放到细胞质中。释放的物质将激活饥饿疗法、化学动力学疗法和蛋白质治疗途径，以确保癌症治疗的高性能。由于其制备简单、毒性低、在肿瘤微环境中可控释放等特点，有望实现蛋白质药物的高效无损递送，满足生物医学应用对协同抗肿瘤治疗精准、高性能的需求。

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Tannic Acid-Assisted Biomineralization Strategy for Encapsulation and Intracellular Delivery of Protein Drugs

Protein therapy has been considered to be one of the most direct and safe ways to regulate cell function and treat tumors. However, safe and effective intracellular delivery of protein drugs is still a key challenge. Herein, we developed a tannic acid-assisted biomineralization strategy for the encapsulation and intracellular delivery of protein drugs. RNase A and glucose oxidase (GOD) were choose as the protein drug model. RNase A, GOD, TA, and Mn²⁺ are mixed in one pot to attain RG@MT, and CaCO₃ coating is subsequently carried out to construct RG@MT@C through biomineralization. Once RG@MT@C is endocytosed, the acidic environment of the lysosome will dissolve the protective layer of CaCO₃ and produce plenty of CO₂ to cause lysosome bursting, ensuring the lysosome escape of the RG@MT@C and thus releasing the generated TA-Mn²⁺, RNase A, and GOD into the cytoplasm. The released substances would activate starvation therapy, chemodynamic therapy, and protein therapy pathways to ensure a high performance of cancer therapy. Due to simple preparation, low toxicity, and controlled release in the tumor microenvironment, we expect it can realize efficient and nondestructive delivery of protein drugs and meet the needs for precise, high performance of synergistically antitumor therapy in biomedical applications.

更新日期：2022-11-02

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