Optimization and characterization of mannose-decorated lipoprotein nanoparticles for the targeting of tumor-associated macrophages
| dc.creator | Dossou, Akpedje | |
| dc.creator | Kapic, Ammar | |
| dc.creator | Sabnis, Nirupama | |
| dc.creator | Fudala, Rafal | |
| dc.creator | Lacko, Andras G. | |
| dc.creator.orcid | 0000-0002-9844-8860 (Dossou, Akpedje) | |
| dc.date.accessioned | 2021-04-30T14:26:07Z | |
| dc.date.available | 2021-04-30T14:26:07Z | |
| dc.date.issued | 2021 | |
| dc.description.abstract | Purpose: Reconstituted high-density lipoprotein nanoparticles (rHDL NPs) have been shown to accumulate into tumors. This effect is achievable because of their small size and their affinity toward the scavenger receptor SR-B1 which is overexpressed in most tumors. Thus, rHDL NPs appear suitable to target tumor-associated macrophages (TAMs) which express SR-B1 as well as the mannose receptor CD206. While cancer cells promote an immunosuppressive (M2) phenotype in TAMs, it has been shown that a re-orientation of TAMs toward an immunostimulating (M1) phenotype results in rapid tumor regression. Because a generalized immunostimulating effect is not desirable, the targeted approach via rHDL NPs offers a safer alternative via selective delivery of an M2-to-M1 reversal agent to TAMs. Vadimezan (also called DMXAA) is such an agent. Consequently, the goal of this study is to develop and characterize a formulation of DMXAA encapsulated in mannose-decorated rHDL NPs. Methods: Six formulations of DMXAA with mannose-decorated rHDL NPs with increasing concentration of the mannose moiety were prepared via microfluidics and characterized via dynamic light scattering, fast protein liquid chromatography, and colorimetric assays for their contents. Results: The formulations decorated with the mannose moiety, displayed larger particle diameters compared to the control rHDL NPs and achieved a drug incorporation efficiency of about 60%. Conclusion: The characteristics of these particles show that the mannose moiety was stably incorporated into the rHDL NPs. Consequently, this formulation is anticipated to selectively target TAMs and, thus, achieve an enhanced therapeutic effect. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12503/30489 | |
| dc.language.iso | en | |
| dc.title | Optimization and characterization of mannose-decorated lipoprotein nanoparticles for the targeting of tumor-associated macrophages | |
| dc.type | poster | |
| dc.type.material | text |