Abstract：
Development of theranostic nanomedicines to tackle glioma remains to be challenging. Here, we present an advanced blood-brain barrier (BBB)-crossing nanovaccine based on cancer cell membrane-camouflaged poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) incorporated with MnO2 and doxorubicin (DOX). We show that the disulfide bond-cross-linked redox-responsive PVCL NGs can be functionalized with dermorphin and imiquimod R837 through cell membrane functionalization. The formed functionalized PVCL NGs having a size of 220 nm are stable, can deplete glutathione, and responsively release both Mn2+ and DOX under the simulated tumor microenvironment to exert the chemo/chemodynamic therapy mediated by DOX and Mn2+, respectively. The combined therapy induces tumor immunogenic cell death to maturate dendritic cells (DCs) and activate tumor-killing T cells. Further, the nanovaccine composed of cancer cell membranes as tumor antigens, R837 as an adjuvant with abilities of DC maturation and macrophages M1 repolarization, and MnO2 with Mn2+-mediated stimulator of interferon gene activation of tumor cells can effectively act on both targets of tumor cells and immune cells. With the dermorphin-mediated BBB crossing, cell membrane-mediated homologous tumor targeting, and Mn2+-facilitated magnetic resonance (MR) imaging property, the designed NG-based theranostic nanovaccine enables MR imaging and combination chemo-, chemodynamic-, and imnune therapy of orthotopic glioma with a significantly decreased recurrence rate.
摘要：
开发治疗性纳米药物以解决神经胶质瘤仍然具有挑战性。这里,我们提出了一种先进的血脑屏障(BBB)交叉纳米疫苗,其基于结合有MnO2和多柔比星(DOX)的癌细胞膜伪装的聚(N-乙烯基己内酰胺)(PVCL)纳米凝胶(NG).我们表明，二硫键交联的氧化还原响应性PVCLNG可以通过细胞膜功能化与dermorphin和咪喹莫特R837功能化。形成的尺寸为220nm的官能化PVCLNG是稳定的，可以消耗谷胱甘肽，并在模拟的肿瘤微环境下响应释放Mn2+和DOX，以发挥DOX和Mn2+介导的化学/化学动力学疗法，分别。联合疗法诱导肿瘤免疫原性细胞死亡以使树突状细胞(DC)成熟并激活肿瘤杀伤T细胞。Further,由癌细胞膜作为肿瘤抗原组成的纳米疫苗，R837作为佐剂，具有DC成熟和巨噬细胞M1复极化的能力，MnO2与Mn2+介导的肿瘤细胞干扰素基因激活的刺激物能有效地作用于肿瘤细胞和免疫细胞的两个靶点。随着dermorphin介导的BBB交叉，细胞膜介导的同源肿瘤靶向，和Mn2+促进磁共振（MR）成像特性，设计的基于NG的theranostic纳米疫苗可实现MR成像和组合化学-，化学动力学-，和原位胶质瘤的imnune治疗，复发率显着降低。
