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Smart Tumor Microenvironmerit-Responsive Nanotheranostic Agent for Effective Cancer Therapy

机译：智能肿瘤微环境反应性纳米治疗剂，可有效治疗癌症。

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摘要

The tumor microenvironment (TME), which includes acidic and hypoxic conditions, severely impedes the therapeutic efficacy of antitumor agents. Herein, MnO2-loaded, bovine serum albumin, and PEG co-modified mesoporous CaSiO3 nanoparticles (CaM-PB NPs) are developed as a nanoplatform with sequential theranostic functions for the engineering of TME. The MnO2 NPs generate O-2 in situ by reacting with endogenous H2O2, relieving the hypoxic state of the TME that further modulates the cancer cell cycle status to S phase, which improves the potency of co-loaded S phase-sensitive chemotherapeutic drugs. After the hypoxia relief, CaM-PB can sustainably release drugs due to the enlarged pores of mesoporous CaSiO3 in the acidic TME, preventing the drug pre-leakage into the blood circulation and insufficient drug accumulation at tumor sites. Moreover, the Mn2+ released from the MnO2 NPs at tumor sites can potentially serve as a diagnostic agent, enabling the identification of tumor regions by T-1-weighted magnetic resonance imaging during therapy. In vivo pharmacodynamics results demonstrate that these synergetic effects caused by CaM-PB NPs significantly contribute to the inhibition of tumor progression. Therefore, the CaM-PB NPs with sequential theranostic functions are a promising system for effective cancer therapy.
机译：包括酸性和低氧条件的肿瘤微环境（TME）严重阻碍了抗肿瘤药的治疗功效。在这里，MnO2负载，牛血清白蛋白和PEG共修饰的介孔CaSiO3纳米粒子（CaM-PB NPs）被开发为具有顺序治疗功能的纳米平台，用于TME工程。 MnO2 NPs通过与内源性H2O2反应原位产生O-2，从而缓解TME的低氧状态，从而进一步将癌细胞周期状态调节为S期，从而提高了共载S期敏感性化学药物的功效。缺氧缓解后，由于酸性TME中介孔CaSiO3的孔扩大，CaM-PB可以持续释放药物，从而防止药物预渗入血液循环和防止肿瘤部位的药物蓄积不足。此外，在肿瘤部位从MnO2 NPs释放的Mn2 +可以潜在地用作诊断剂，从而能够在治疗过程中通过T-1加权磁共振成像来鉴定肿瘤区域。体内药效学结果表明，由CaM-PB NP引起的这些协同作用显着促进了肿瘤进展的抑制。因此，具有顺序治疗功能的CaM-PB NP是有效的癌症治疗的有希望的系统。

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  • 来源
    《Advanced Functional Materials》 |2020年第17期|2000486.1-2000486.11|共11页
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    Shanghai Univ Tradit Chinese Med Inst Chinese Mat Med MOE Key Lab Standardizat Chinese Med 1200 Cailun Rd Zhangjiang Hitech Pk Shanghai 201203 Peoples R China|Shanghai Univ Tradit Chinese Med Inst Chinese Mat Med Shanghai Key Lab Compound Chinese Med 1200 Cailun Rd Zhangjiang Hitech Pk Shanghai 201203 Peoples R China|Chinese Acad Sci Shanghai Inst Mat Med 501 Haike Rd Shanghai 201203 Peoples R China;

    Shanghai Univ Tradit Chinese Med Inst Chinese Mat Med MOE Key Lab Standardizat Chinese Med 1200 Cailun Rd Zhangjiang Hitech Pk Shanghai 201203 Peoples R China|Shanghai Univ Tradit Chinese Med Inst Chinese Mat Med Shanghai Key Lab Compound Chinese Med 1200 Cailun Rd Zhangjiang Hitech Pk Shanghai 201203 Peoples R China;

    Univ Wisconsin Dept Radiol Madison WI 53705 USA;

    Chinese Acad Sci Shanghai Inst Mat Med 501 Haike Rd Shanghai 201203 Peoples R China;

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  • 关键词

    hypoxia relief; mesoporous calcium silicate; sequential functions; sustained drug release; synergetic effects;

    机译：缺氧缓解;介孔硅酸钙;顺序功能;持续释放药物;协同效应;

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