Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer. Sci Adv 2020 Jan;6(3):eaax5032
Date
01/31/2020Pubmed ID
31998834Pubmed Central ID
PMC6962042DOI
10.1126/sciadv.aax5032Scopus ID
2-s2.0-85078092406 (requires institutional sign-in at Scopus site) 233 CitationsAbstract
While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8+ T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
Author List
Huang KW, Hsu FF, Qiu JT, Chern GJ, Lee YA, Chang CC, Huang YT, Sung YC, Chiang CC, Huang RL, Lin CC, Dinh TK, Huang HC, Shih YC, Alson D, Lin CY, Lin YC, Chang PC, Lin SY, Chen YAuthor
Donia Alson Postdoctoral Researcher 2 in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents, Immunological
Biomarkers
Biomarkers, Tumor
Calcium Phosphates
Cytokines
Dendritic Cells
Drug Delivery Systems
Gene Transfer Techniques
Genetic Therapy
Humans
Immunogenetic Phenomena
Immunotherapy
Lipids
Male
Membrane Proteins
Mice
Molecular Targeted Therapy
Nanoparticles
Nanotechnology
Neoplasms
Plasmids
RNA, Small Interfering
Signal Transduction
Theranostic Nanomedicine
