Dual-Targeted Lipid Nanotherapeutic Boost for Chemo-Immunotherapy of Cancer
© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 34(2022), 13 vom: 15. Apr., Seite e2106350 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2022
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article HO1-targeted nanotherapeutics cancer-targeted therapy chemo-immunotherapy ionizable lipid nanoparticle targeted lipid nanoparticle Lipid Nanoparticles Lipids Liposomes |
| Zusammenfassung: | © 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH. Chemo-immunotherapy is a combination of "standard-of-care" chemotherapy with immunotherapy and it is considered the most advanced therapeutic modality for various types of cancers. However, many cancer patients still poorly respond to current regimen of chemo-immunotherapy and suggest nanotherapeutics as a boosting agent. Recently, heme oxygenase-1 (HO1) is shown to act as an immunotherapeutic molecule in tumor myeloid cells, in addition to general chemoresistance function in cancer cells suggesting that HO1-targeted therapeutics can become a novel, optimal strategy for boosting chemo-immunotherapy in the clinic. Currently the available HO1-inhibitors demonstrate serious adverse effects in clinical use. Herein, tumor myeloid cell- and cancer cell-dual targeted HO1-inhibiting lipid nanotherapeutic boost (T-iLNTB) is developed using RNAi-loaded lipid nanoparticles. T-iLNTB-mediated HO1-inhibition sensitizes cancer cells to "standard-of-care" chemotherapeutics by increasing immunogenic cell death, and directly reprograms tumor myeloid cells with distinguished phenotype. Furthermore, tumor myeloid cell reprogramming by T-iLNTB induces CD8+ cytotoxic T cell recruitment, which drives "Cold-to-Hot" transition and correlates with improved responsiveness to immune checkpoint inhibitor in combination therapy. Finally, ex vivo study proves that HO1-inhibition directly affects tumor macrophage differentiation. This study demonstrates the potential of T-iLNTB as a novel therapeutic modality for boosting chemo-immunotherapy |
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| Beschreibung: | Date Completed 04.04.2022 Date Revised 05.04.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202106350 |