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一种 pH 响应性聚合物包覆的 CaOas 氧生成纳米颗粒用于增强肿瘤的化学-光动力协同治疗。

A pH-responsive polymer-coated CaOas oxygen-generating nanoparticlefor enhanced chemo-photodynamic synergistic therapy against tumors.

机构信息

College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu, 241000, Anhui, People's Republic of China.

出版信息

Nanotechnology. 2023 Aug 21;34(45). doi: 10.1088/1361-6528/aced9c.

Abstract

Photodynamic therapy (PDT) has emerged as an efficient strategy for tumor treatment. However, Insufficient amounts of inherent hypoxia and intrinsic hydrogen peroxide (HO) in the tumor microenvironment severely constrained PDT, as oxygen is the critical substrate for photosensitivity reaction. Here, a pH-responsive HOand Oself-supplying hybrid nanoparticle was designed. Through, the calcium peroxide (CaO) as carriers loading a chemotherapeutic drug a photosensitizer 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) and doxorubicin (DOX), was covered with polyacrylic acid (PAA) to build up a feature material DOX-TAPP-CaO@OA@PAA (denoted as DTCOP) through the reverse microemulsion method. In the acidic tumor microenvironment conditions exposing the water-sensitive CaOnanocore to generate hydrogen peroxide (HO) and O, the self-supplied Oalleviates hypoxia to enhance the PDT, and releasing DOX and TAPP. Synthetic characterization shows that the succeeded synthesized Nanocarriers could effectively carry DOX and TAPP to the tumor site and release Oat the low pH of TME. And the experimental results demonstrated that this interpose exogenous oxygen strategy is efficient at inhibition of tumor growth bothand. The nanocomposite exhibits excellent biocompatibility and the ability to inhibit tumor growth and has significant potential for the treatment of hypoxic tumors.

摘要

光动力疗法 (PDT) 已成为治疗肿瘤的有效策略。然而,肿瘤微环境中内在的缺氧和内在的过氧化氢 (HO) 含量不足严重限制了 PDT 的发展,因为氧气是光敏反应的关键底物。在这里,设计了一种 pH 响应的 HO 和 O 自供应混合纳米粒子。通过将过氧钙 (CaO) 作为载体,负载一种化疗药物、一种光敏剂 5,10,15,20-四(4-氨基苯基)卟啉 (TAPP) 和阿霉素 (DOX),用聚丙烯酸 (PAA) 覆盖,通过反相微乳液法构建了一种特征材料 DOX-TAPP-CaO@OA@PAA(表示为 DTCOP)。在酸性肿瘤微环境条件下,暴露于水敏性 CaOnanocore 会产生过氧化氢 (HO) 和 O,自供应的 O 缓解缺氧以增强 PDT,并释放 DOX 和 TAPP。合成表征表明,成功合成的纳米载体可以有效地将 DOX 和 TAPP 带到肿瘤部位,并在 TME 的低 pH 值下释放 O。实验结果表明,这种介入外源氧的策略在抑制肿瘤生长方面非常有效。该纳米复合材料具有优异的生物相容性和抑制肿瘤生长的能力,具有治疗缺氧肿瘤的巨大潜力。

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