Doctoral thesis
Open access

Design of STING ligand nanoparticles for improved cold cancer immunotherapy

ContributorsPetrovic, Marijaorcid
Imprimatur date2022-11-03
Defense date2022-09-16

Immunotherapy sees its effectiveness limited by the resistance of poorly immunogenic “cold” tumors, such as found in glioblastoma, prostate can or pancreatic cancer. In order to reduce this resistance, one strategy consists in modifying the tumor microenvironment (TME) towards the “hot” phenotype, infiltrated by the immune system. Therefore, we used in this work the activation of the stimulator of the interferon gene (STING) of the innate immunity pathway, targeting the cytosol of antigen-presenting cells (APC) in the TME. We opted for cGAMP, a STING ligand owing negative charge. To enable APC targeting and efficient transfection to the cytosol of the APCs (of both dendritic cells (DC) and macrophages (M)) as well as protection against enzymes, positively charged carriers are required. Therefore, polyethyleneimine (PEI) and sugar-coated polyamidoamine (PAMAM) are investigated as carriers for the local administration of cGAMP to "cold" type tumors. For this, we formulated nanoparticles (NPs) with cGAMP through electrostatic interactions. We have also studied an “antimiR” oligonucleotide that inhibits microRNA 25/93, allowing the reactivation of the STING pathway in glioblastoma. In order to increase the quality of NP formulations, orthogonal techniques such as DLS, NTA, AF4, VideoDrop, nanoFCM, UPLC-UV and SEM were used to characterize the critical quality attributes (CQA) of NPs.

Research group
Citation (ISO format)
PETROVIC, Marija. Design of STING ligand nanoparticles for improved cold cancer immunotherapy. 2022. doi: 10.13097/archive-ouverte/unige:165945
Main files (2)

Technical informations

Creation12/14/2022 3:31:00 PM
First validation12/14/2022 3:31:00 PM
Update time03/16/2023 10:19:20 AM
Status update03/16/2023 10:19:16 AM
Last indexation09/18/2023 9:42:33 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack