Department of Pharmacy, The Affiliated Hospital of Jiangnan University (Original Area of Wuxi Third People's Hospital), China.
Department of Pharmacy, The Affiliated Hospital of Jiangnan University (Original Area of Wuxi Third People's Hospital), China.
Biomed Pharmacother. 2020 Jun;126:110046. doi: 10.1016/j.biopha.2020.110046. Epub 2020 Mar 4.
Cancer vaccine is widely considered as a powerful tool in immunotherapy. In particular, the effective antigen processing and presentation natures of dendritic cell (DC) have made it a promising target for the development of therapeutic vaccine for cancer treatment. Here in our study, a versatile cancer cell membrane (CCM) coated calcium carbonate (CC) nanoparticles (MC) that capable of generating in situ tumor-associated antigens (TAAs) for DC vaccination is developed. Low-dose doxorubicin hydrochloride (Dox) could be encapsulated in the CC core of MC to trigger immunogenic cell death (ICD) while chlorins e6 (Ce6), a commonly adopted photosensitizer, was loaded in the CCM of MC for effective photodynamic therapy (PDT) through the generation of reactive oxygen species (ROS) to finally construct the vaccine (MC/Dox/Ce6). Most importantly, our in-depth study revealed the treatment of MC/Dox/Ce6 was able to elicit TAAs population and DC recruitment, triggering the following immune response cascade. In particular, the recruited DC cells could be stimulated in situ for effective vaccinations. Both in vitro and in vivo experiments suggested the capability of this all-in-one DDS to enhance DCs maturation to finally result in effective inhibition of both primary and distant growth of breast cancer upon single administration of low dose Dox and Ce6.
癌症疫苗被广泛认为是免疫疗法中的一种强大工具。特别是树突状细胞（DC）有效的抗原处理和呈递特性使其成为癌症治疗治疗性疫苗开发的有前途的目标。在我们的研究中，开发了一种多功能的癌细胞膜（CCM）包覆碳酸钙（CC）纳米粒子（MC），能够原位产生用于 DC 疫苗接种的肿瘤相关抗原（TAA）。低剂量盐酸多柔比星（Dox）可包裹在 MC 的 CC 核心中，引发免疫原性细胞死亡（ICD），而氯乙酮 e6（Ce6），一种常用的光敏剂，可加载在 MC 的 CCM 中，通过产生活性氧（ROS）进行有效的光动力疗法（PDT），最终构建疫苗（MC/Dox/Ce6）。最重要的是，我们的深入研究表明，MC/Dox/Ce6 的治疗能够引发 TAA 群体和 DC 募集，引发以下免疫反应级联。特别是，募集的 DC 细胞可以原位刺激，进行有效的疫苗接种。体外和体内实验均表明，这种一体化 DDS 能够增强 DC 的成熟，最终在单次低剂量 Dox 和 Ce6 给药后有效抑制乳腺癌的原发和远处生长。
