Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors  

作　　者：Yuling Mao Xiudan Wang Caishun Chen Qinfu Zhao Yanfeng Liu Jinghai Zhang Siling Wang 

机构地区：[1]Department of Pharmaceutics,School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Department of Biomedical Engineering,School of Medical Devices,Shenyang Pharmaceutical University,Shenyang 110016,China [3]School of Life Science and Bio-pharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第12期4501-4518,共18页药学学报（英文版）

基　　金：This work was supported by China Postdoctoral Science Foundation(No.2020T130434,China);National Natural Science Foundation of China(No.82073798,China);National Natural Science Foundation of China(No.82104107,China);National Basic Research Program of China(973 Program)(No.2015CB932100,China);Doctoral Start-up Foundation of Liaoning Province(No.2021-BS-127,China).

摘　　要：Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment,in addition to improving oral bioavailability relative to other means of delivery of oral drugs.Here,inspired by the specific invasion route of intestinal microorganisms,we pioneered an immune-awakening Saccharomyces-inspired mesoporous silicon nanoparticle(yMSN)for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic pathway.Encouragingly,yMSN high-loaded tumor-specific antigens(OVA,11.9%)and anti-tumor drugs(Len,28.6%)with high stability,namely Len/OVA/yMSN,efficiently co-delivered OVA and Len to their desired target sites.Moreover,yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages,strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor microenvironment.Surprisingly,Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing mice.This high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment,and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases.

关 键 词：Oral delivery Saccharomyces-inspired Immune-awakening nanoparticles Intestinal lymphatic pathway Vaccine delivery Cascade-targeted delivery Awakening the innate/adaptive immunity CO-DELIVERY 

分 类 号：R943[医药卫生—药剂学]