Key Laboratory of Drug-Targeting and Drug Delivery Systems of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Key Laboratory of Drug-Targeting and Drug Delivery Systems of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
J Control Release. 2020 Jun 10;322:300-311. doi: 10.1016/j.jconrel.2020.03.045. Epub 2020 Mar 30.
To date, cancer phototherapy remains as an unsatisfactory method of cancer treatment due to the high probability of cancer recurrence - an effect that is partly driven by tumor-driven immunosuppression. Therefore, we propose inducing adequate immune responses after photo tumor ablation may be critical to achieve a long term therapeutic effect of phototherapy. Here, we engineered the photosensitizer chlorin e6 (Ce6) and the time-honored immunoadjuvant aluminum hydroxide into bovine serum albumin by albumin-based biomineralization as a novel nanosystem (Al-BSA-Ce6 NPs). After intravenous injection, the nanoparticles not only destroyed tumor cells effectively but also protected animals against tumor rechallenge and metastasis by strongly inducing a systemic anti-tumor immune response. Subsequent analysis demonstrated T cells accumulated in lymph nodes and infiltrated the tumor site, elevating levels of immune indicators including serum antibody, cytokine level and higher proportions of cytotoxic T cells and Th1 cells. These protective effects were not observed with commercially available alumina gels, or when the aluminum hydroxide in the nanoparticles was replaced with ferric hydroxide. Therefore, we present Al-BSA-Ce6 NPs as a novel and unique system for alumina adjuvants that serves as an effective approach for cancer therapy.
迄今为止，由于癌症复发的可能性很高——这种效果部分是由肿瘤驱动的免疫抑制所驱动，癌症光疗仍然是一种不尽人意的癌症治疗方法。因此，我们提出在光肿瘤消融后诱导足够的免疫反应对于实现光疗的长期治疗效果可能是至关重要的。在这里，我们通过基于白蛋白的生物矿化将光敏剂氯乙酮（Ce6）和历史悠久的免疫佐剂氢氧化铝设计到牛血清白蛋白中，作为一种新型纳米系统（Al-BSA-Ce6 NPs）。静脉注射后，纳米颗粒不仅有效地破坏了肿瘤细胞，而且通过强烈诱导全身性抗肿瘤免疫反应，保护动物免受肿瘤再挑战和转移。随后的分析表明，T 细胞在淋巴结中积累并浸润肿瘤部位，提高了免疫指标的水平，包括血清抗体、细胞因子水平以及更高比例的细胞毒性 T 细胞和 Th1 细胞。这些保护作用在市售的氧化铝凝胶中观察不到，或者当纳米颗粒中的氢氧化铝被氢氧化铁取代时也观察不到。因此，我们提出 Al-BSA-Ce6 NPs 作为一种新型独特的氧化铝佐剂系统，为癌症治疗提供了一种有效的方法。
