Porous Silicon Nanocarriers Boost the Immunomodulation of Mitochondria-Targeted Bovine Serum Albumins on Macrophage Polarization
- ACS Nano. 2023 Jan 4. doi: 10.1021/acsnano.2c07439.
- 1. College of Science, Nanjing Forestry University, Nanjing210037, China.
- 2. State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing210023, China.
- 3. Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AVGroningen, The Netherlands.
- 4. W. J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AVGroningen, The Netherlands.
- 5. Department of Geriatric Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou325027, China.
The development of nanosystems with intrinsic immunomodulatory effects on macrophage polarization is important for the macrophage-targeted immunotherapy. Here, mitochondria-targeted bovine serum albumins (BSAs) via the conjugation of fluorescent, lipophilic, and cationic rhodamine 110 molecules can efficiently enhance the gene expression of the proinflammatory phenotype of macrophages and correspondingly inhibit the gene expression of their anti-inflammatory phenotype. On this basis, porous silicon nanocarriers can further boost the immunomodulation of these mitochondria-targeted BSAs in vitro or in vivo, accompanied by the secretion of proinflammatory mediators including tumor necrosis factor α, nitric oxide, and Reactive Oxygen Species (ROS). Meanwhile, BSA coatings can also improve the biocompatibility of porous silicon nanoparticulate cores on macrophages. Finally, the mechanism investigations demonstrate that porous silicon nanocarriers can efficiently deliver mitochondria-targeted BSA into macrophages to generate mitochondrial ROS via the interference with mitochondrial respiratory chains, which can further trigger the downstream signaling transduction pathways for the proinflammatory transition. Considering the good biosafety and versatile loading capability, this developed porous silicon@BSA nanosystem with a strong proinflmmatory regulatory effect has important potential on the combinatorial chemoimmunotherapy against Cancer or viral/bacterial-related infectious diseases.