PXD045220-1

PXD045220 is an original dataset announced via ProteomeXchange.

Title	Proteins identified from E. coli MG1655-origined OMVs in the paper of “On-demand Editing Macrophages Enable Specific Phagocytosis and Drug Exosome Generation for Solid Tumour Cytotherapy”
Description	Cytotherapy is a revolutionary therapeutic agent representing the forefront of current cancer therapy, but its poor efficacy in the treatment of solid tumours remains challenging. Integration of tumour infiltration, targeted elimination and tumour microenvironment (TME) regulation functions in designing effective cytopharmaceuticals for solid tumours is necessary. Here, we designed on-demand editing macrophages (RILO-M1-G) constructed by surface glypican-3 (GPC3) peptide anchoring and inner R848/INCB024360-lipid particle (RILO) packing to combat hepatocellular carcinoma (HCC). Based on the tumour tendency and deep penetration of macrophages, the anchored GPC3 peptide on the membrane surface promoted macrophage-tumour cell recognition, thus enhancing specific tumour targeting and phagocytosis of tumour cells with high GPC3 expression. The packed RILOs were wrapped by C16-ceramide fused Escherichia coli-originated outer membrane vesicles (OMVs). OMVs facilitated RILO internalization through caveolin-mediated endocytosis to maintain a suitable nanostructure, C16-ceramide induced membrane invagination and exosome generation, leading to the release of packed RILOs through exosomes. These exosomes containing the TLR7/8 agonist R848 and IDO1 inhibitor INCB024360 enabled remodelling of the immunosuppressive TME by regulating the tumour-associated macrophage phenotype and enhancing T-cell viability. Furthermore, treatments with RILO-M1-G exerted remarkable therapeutic efficacy in a H22 tumour-bearing mouse model, rechallenged tumour model and orthotopic HCC mouse model compared with that of first-line HCC therapy. Overall, RILO-M1-G offered a new cytotherapeutic strategy for meeting the clinical demands of solid tumour treatment.
HostingRepository	iProX
AnnounceDate	2023-09-08
AnnouncementXML	Submission_2024-10-31_19:26:20.024.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jinhu Liu
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-08 04:44:00	ID requested
⏵ 1	2024-10-31 19:26:20	announced

Dataset with its publication pending

submitter keyword: Cytotherapy, Macrophage, On-demand Editing, Glypican-3, Drug Exosome, Hepatocellular Carcinoma

Na Zhang
contact affiliation	Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University
contact email	zhangnancy9@sdu.edu.cn
lab head
Jinhu Liu
contact affiliation	Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University
contact email	liujinhu19980218@126.com
dataset submitter

iProX dataset URI