Key Laboratory of Drug-Targeting and Drug Delivery System 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, China.
Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, China; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Control Release. 2020 May 10;321:589-601. doi: 10.1016/j.jconrel.2020.02.043. Epub 2020 Feb 28.
The current nanomedicines for cancer therapy based on the enhance permeability and retention (EPR) effect remain insufficient to satisfy the clinical need, and the challenges hindering nanomedicines delivery should be conquered for strong therapeutic efficacy. To address these problems, a membrane-coated laser-responsive shape changeable nanomedicine, I-P@NPs@M, is reported. The covering macrophage membrane promotes the circulation and tumor targeting of nanomedicines. Then the chlorin e6 (Ce6) in I-P@NPs@M can convert 650 nm laser into reactive oxygen species (ROS) to trigger the spherical micelles changing into nanofibers for strong retention in tumor region, consequently the linear nanofibers long locate and sustainably release drugs. On the other hand, the ROS not only directly kills tumor cells by photodynamic therapy but stimulates the dimeric paclitaxel (PTX) generating monomeric PTX. The combinational chemo- photodynamic therapy heavily suppresses tumor growth and inducing immunogenic cell death, which is synergistic with Indoximod (IND) inhibiting the IDO pathway to activate immune response for immunotherapy. By chemotherapy, photodynamic therapy and immunotherapy gathering, the treatment of I-P@NPs@M + laser shows the best antitumor effect, resulting in 85.27 ± 12.80% suppression of breast cancer in mice model, and also remarkably inhibits lung metastasis.
目前基于增强渗透和滞留（EPR）效应的癌症治疗纳米药物仍不足以满足临床需求，为了获得强大的治疗效果，应该克服阻碍纳米药物传递的挑战。为了解决这些问题，报道了一种膜包覆的激光响应形状变化纳米药物，I-P@NPs@M。巨噬细胞膜的覆盖促进了纳米药物的循环和肿瘤靶向。然后，I-P@NPs@M 中的氯己定（Ce6）可以将 650nm 激光转化为活性氧（ROS），从而触发球形胶束转变为纳米纤维，在肿瘤区域内强烈保留，从而使线性纳米纤维长时间定位并持续释放药物。另一方面，ROS 不仅通过光动力疗法直接杀死肿瘤细胞，还刺激二聚紫杉醇（PTX）生成单体 PTX。联合化疗-光动力疗法强烈抑制肿瘤生长并诱导免疫原性细胞死亡，这与 Indoximod（IND）抑制 IDO 途径以激活免疫反应进行免疫治疗协同作用。通过化疗、光动力治疗和免疫治疗的联合，I-P@NPs@M+激光的治疗效果最佳，在小鼠模型中抑制乳腺癌的效果达到 85.27±12.80%，并且还显著抑制了肺转移。
