Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy
Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy
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DOI：
10.1016/j.ijpharm.2020.119787
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发表时间：
2020-11-15
影响因子：
5.8
通讯作者：
Betancourt, Tania
中科院分区：
文献类型：
--
作者：
Aghda, Niloofar Heshmati;Abdulsahib, Shahad M.;Betancourt, Tania
利用纳米药物诱导免疫原性细胞死亡是一种新的策略，旨在提高肿瘤的免疫原性，从而为进一步的免疫治疗奠定基础。在这项研究中，我们开发了一种用于联合化疗和光热治疗的纳米颗粒制剂，仅基于FDA批准的产品中使用的材料，并研究了联合治疗对人乳腺癌细胞MDA-MB-231的生长抑制和诱导免疫原性细胞死亡的影响。该配方由类似于108 nm的聚乳酸-b-甲氧基聚乙二醇纳米颗粒组成，该纳米颗粒携带用于化疗的阿霉素和用于光热治疗的吲哚青绿。在808 nm的半导体激光照射下，0.3 mg/mL的纳米颗粒悬浮液将介质温度提高到10摄氏度。体外研究表明，与单独单独治疗相比，激光辅助吲哚青绿介导的光热治疗和阿霉素介导的化疗相结合有效地根除了癌细胞，并导致了最高水平的损伤相关分子模式呈现(钙网蛋白、高迁移率族蛋白1和三磷酸腺苷)。这些结果表明，与单独化疗或光热治疗相比，我们的纳米颗粒介导的组合方法导致了最强烈的免疫原性细胞死亡，使其成为未来与癌症免疫治疗相结合的体内研究的有效选择。
The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nano particle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of similar to 108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy. A 0.3 mg/mL suspension of NPs increased the medium temperature up to 10 degrees C upon irradiation with an 808-nm diode laser. In vitro studies showed that combination of laser assisted indocyanine green-mediated photothermal therapy and doxorubicinmediated chemotherapy effectively eradicated cancer cells and resulted in the highest level of damage-associated molecular pattern presentation (calreticulin, high mobility group box 1, and adenosine triphosphate) compared to the individual treatments alone. These results demonstrate that our nanoparticle-mediated combinatory approach led to the most intense immunogenic cell death when compared to individual chemotherapy or photothermal therapy, making it a potent option for future in vivo studies in combination with cancer immunotherapies.