An Oral Nanomedicine Elicits <i>In Situ</i> Vaccination Effect against Colorectal Cancer

作者全名："Zu, Menghang; Ma, Ya; Zhang, Jun; Sun, Jianfeng; Shahbazi, Mohammad-Ali; Pan, Guoqing; Reis, Rui L.; Kundu, Subhas C.; Liu, Jinyao; Xiao, Bo"

作者地址："[Zu, Menghang; Ma, Ya; Pan, Guoqing; Xiao, Bo] Southwest Univ, Coll Sericulture Text & Biomass Sci, State Key Lab Resource Insects, Chongqing 400715, Peoples R China; [Zhang, Jun] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China; [Sun, Jianfeng] Univ Oxford, Botnar Res Ctr, Nuffield Dept Orthoped Rheumatol & Musculoskeletal, Oxford OX3 7LD, England; [Shahbazi, Mohammad-Ali] Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Engn, NL-9713 AV Groningen, Netherlands; [Shahbazi, Mohammad-Ali] Univ Groningen, WJ Kolff Inst Biomed Engn & Mat Sci, NL-9713 AV Groningen, Netherlands; [Reis, Rui L.; Kundu, Subhas C.] Univ Minho, Headquarters European Inst Excellence Tissue Engn, I3Bs Res Inst Biomat Biodegradables & Biomimet, 3Bs Res Grp, P-4805017 Barco, Guimaraes, Portugal; [Reis, Rui L.; Kundu, Subhas C.] ICVS 3Bs PT Govt Associate Lab, P-4800058 Braga, Guimaraes, Portugal; [Liu, Jinyao] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst,Shanghai Key Lab Nucleic Acid C, Shanghai 200127, Peoples R China"

通信作者："Xiao, B (通讯作者)，Southwest Univ, Coll Sericulture Text & Biomass Sci, State Key Lab Resource Insects, Chongqing 400715, Peoples R China.; Liu, JY (通讯作者)，Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst,Shanghai Key Lab Nucleic Acid C, Shanghai 200127, Peoples R China."

来源：ACS NANO

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001154904400001

JCR分区：Q1

影响因子：17.1

年份：2024

卷号：18

期号：4

开始页：3651

结束页：3668

文献类型：Article

关键词：oral administration; nanomedicine; mucus penetration; in situ vaccination; immunotherapy; colorectal cancer

摘要："Oral administration is the most preferred approach for treating colon diseases, and in situ vaccination has emerged as a promising cancer therapeutic strategy. However, the lack of effective drug delivery platforms hampered the application of in situ vaccination strategy in oral treatment of colorectal cancer (CRC). Here, we construct an oral core-shell nanomedicine by preparing a silk fibroin-based dual sonosensitizer (chlorin e6, Ce6)- and immunoadjuvant (imiquimod, R837)-loaded nanoparticle as the core, with its surface coated with plant-extracted lipids and pluronic F127 (p(127)). The resultant nanomedicines (Ce6/R837@Lp(127)NPs) maintain stability during their passage through the gastrointestinal tract and exert improved locomotor activities under ultrasound irradiation, achieving efficient colonic mucus infiltration and specific tumor penetration. Thereafter, Ce6/R837@Lp(127)NPs induce immunogenic death of colorectal tumor cells by sonodynamic treatment, and the generated neoantigens in the presence of R837 serve as a potent in situ vaccine. By integrating with immune checkpoint blockades, the combined treatment modality inhibits orthotopic tumors, eradicates distant tumors, and modulates intestinal microbiota. As the first oral in situ vaccination, this work spotlights a robust oral nanoplatform for producing a personalized vaccine against CRC."

基金机构："National Natural Science Foundation of China [82072060, 22008201]; National Natural Science Foundation of China [SWU-XDPY22006]; Fundamental Research Funds for the Central Universities [SCMR202106]; Open Fund of State Key Laboratory of Southwestern Chinese Medicine Resources [2022NSCQ-JQX5279]; Distinguished Young Scholars of Chongqing [cstc2020jcyj-msxmX0292]; Natural Science Foundation Project of Chongqing"

基金资助正文："This study was supported by the National Natural Science Foundation of China (82072060 and 22008201), the Fundamental Research Funds for the Central Universities (SWU-XDPY22006), the Open Fund of State Key Laboratory of Southwestern Chinese Medicine Resources (SCMR202106), the Distinguished Young Scholars of Chongqing (2022NSCQ-JQX5279), and the Natural Science Foundation Project of Chongqing (cstc2020jcyj-msxmX0292). S.C. Kundu wishes to express his sincere thanks for supporting him with facilities by the Southwest University for the collaborative research visit at the State Key Laboratory of Resource Insects."