Smart Tumor Microenvironment-Responsive Nanotheranostic Agent for Effective Cancer Therapy
Smart Tumor Microenvironment-Responsive Nanotheranostic Agent for Effective Cancer Therapy
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用于有效癌症治疗的智能肿瘤微环境响应纳米治疗剂
DOI：
10.1002/adfm.202000486
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发表时间：
2020-02-28
影响因子：
19
通讯作者：
Wang, Zheng-tao
中科院分区：
文献类型：
--
作者：
Guo, Shi-yan;Sun, Di;Wang, Zheng-tao
肿瘤微环境（TME），包括酸性和缺氧条件，严重阻碍了抗肿瘤药物的治疗效果。在此，MnO 2负载，牛血清白蛋白，和PEG共改性介孔CaSiO 3纳米粒子（CaM-PB NPs）开发作为一个纳米平台，具有连续的治疗诊断功能的工程TME。MnO 2纳米颗粒通过与内源性H2 O2反应原位产生O-2，缓解TME的缺氧状态，进一步将癌细胞周期状态调节至S期，这提高了共负载的S期敏感性化疗药物的效力。缺氧缓解后，CaM-PB可在酸性TME中由于介孔CaSiO 3的孔增大而持续释放药物，防止药物预渗漏进入血液循环和肿瘤部位药物蓄积不足。此外，在肿瘤部位从MnO 2 NPs释放的Mn 2+可以潜在地用作诊断剂，使得能够在治疗期间通过T-1加权磁共振成像来识别肿瘤区域。体内药效学结果表明，由CaM-PB NPs引起的这些协同作用显著有助于抑制肿瘤进展。因此，具有序贯治疗诊断功能的CaM-PB纳米粒是有效治疗癌症的有希望的系统。
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.