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Dual functional immunostimulatory polymeric prodrug carrier with pendent indoximod for enhanced cancer immunochemotherapy
| Content Provider | Scilit |
|---|---|
| Author | Wan, Zhuoya Sun, Jingjing Xu, Jieni Moharil, Pearl Chen, Jing Xu, Junchi Zhu, Junjie Li, Jiang Huang, Yixian Xu, Pengfei Ma, Xiaochao Xie, Wen Lu, Binfeng Li, Song |
| Copyright Year | 2019 |
| Description | Journal: Acta Biomaterialia Immunotherapy based on checkpoint blockade has been regarded as one of the most promising approaches towards many types of cancers. However, low response rate hinders its application due to insufficient tumor immunogenicity and immunosuppressive tumor microenvironment. To achieve an overall enhanced therapeutic outcome, we developed a dual-functional immuno-stimulatory polymeric prodrug carrier modified with pendent indoximod, an indoleamine 2,3-dioxygenase (IDO) inhibitor that can be used to reverse immune suppression, for co-delivery of Doxorubicin (Dox), a hydrophobic anticancer agent that can promote immunogenic cell death (ICD) and elicit antitumor immunity. The resulted carrier denoted as POEG-b-PVBIND, consisting of poly (oligo (ethylene glycol) methacrylate) (POEG) hydrophilic blocks and indoximod conjugated hydrophobic blocks, is rationally designed to improve immunotherapy by synergistically modulating the tumor microenvironment (TME). Our data showed that Dox-triggered ICD promoted intra-tumoral infiltration of $CD8^{+}$ T cells and IFN-γ-production by $CD8^{+}$ T cells. Meanwhile, cleaved indoximod significantly increased $CD8^{+}$ T cell infiltration while reducing the immunosuppressive T regulatory cells (Tregs). More importantly, Dox/POEG-b-PVBIND micelles led to significantly improved tumor regression in an orthotopic murine breast cancer model compared to both Dox-loaded POEG-b-PVB micelles (a control inert carrier) and POEG-b-PVBIND micelles alone, confirming combination effect of indoximod and Dox in improving the overall antitumor activity. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513707/pdf |
| Ending Page | 313 |
| Page Count | 14 |
| Starting Page | 300 |
| ISSN | 17427061 |
| e-ISSN | 18787568 |
| DOI | 10.1016/j.actbio.2019.03.048 |
| Journal | Acta Biomaterialia |
| Volume Number | 90 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2019-03-28 |
| Access Restriction | Open |
| Subject Keyword | Journal: Acta Biomaterialia Immunochemotherapy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry Molecular Biology Biomaterials Biomedical Engineering Biotechnology |
