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聚氨基酸钙化纳米杂化物诱导免疫原性细胞死亡,增强化疗和化疗光动力协同治疗。

Polyamino acid calcified nanohybrids induce immunogenic cell death for augmented chemotherapy and chemo-photodynamic synergistic therapy.

机构信息

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Materials and Energy and Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing 400715, P. R. China.

Pediatric Research Institute, Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong 518038, P. R. China.

出版信息

Theranostics. 2021 Sep 21;11(19):9652-9666. doi: 10.7150/thno.64354. eCollection 2021.

DOI:10.7150/thno.64354
PMID:34646391
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8490510/
Abstract

Monotherapy for cancer treatment is limited by unstable efficacy and uncontrollable toxic side effects, while the multifunctional nanoplatform with complex preparation process cannot avoid the potential toxicity of each functional component. We exploited tumor-specific activated polyamino acid calcified nanoparticles (CHC NPs) as new-type oxidative stress amplification of anticancer drugs building a safe and biodegradable multifunctional nanoplatform. Giving priority to chemotherapy, and synergizing chemodynamic therapy (CDT) with photodynamic therapy (PDT), this strategy was to achieve enhanced chemotherapy, simultaneously inducing immunogenic cell death and inhibiting tumor cell invasion. Based on amorphous calcium carbonate, pH-responsive nanocarrier was prepared with classical chemotherapeutic drug 10-hydroxycamplothecin (HCPT) and photosensitizer Chlorin e6 (Ce6) to realize multifunctional nanotheranostics. Inventive calcified nanohybrids, where topoisomerase inhibited by HCPT to prevent DNA synthesis, the generation of •OH induced Fenton reaction, along with a large amount of O produced by Ce6, might be a promising strategy for anti-tumor combination therapy in clinical translation.

摘要

癌症的单药治疗受到疗效不稳定和不可控的毒副作用的限制,而多功能纳米平台具有复杂的制备工艺,无法避免每个功能组件的潜在毒性。我们利用肿瘤特异性激活的聚氨基酸钙化纳米颗粒 (CHC NPs) 作为新型抗癌药物的氧化应激放大剂,构建了一种安全可生物降解的多功能纳米平台。该策略以化疗为主,协同化学动力学治疗 (CDT) 和光动力治疗 (PDT),以实现增强的化疗,同时诱导免疫原性细胞死亡和抑制肿瘤细胞侵袭。基于无定形碳酸钙,用经典化疗药物 10-羟基喜树碱 (HCPT) 和光敏剂 Chlorin e6 (Ce6) 制备了 pH 响应型纳米载体,实现了多功能纳米治疗。创新的钙化纳米杂化物中,HCPT 抑制拓扑异构酶以阻止 DNA 合成,•OH 的产生引发 Fenton 反应,同时 Ce6 产生大量的 O,可能是临床转化中抗肿瘤联合治疗的有前途的策略。

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