Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPα Checkpoint Blockade for Efficient Treatment of Colon Cancer
Abstract
:1. Introduction
2. Results and Discussion
2.1. Characterization of LPs (Blank Liposomes), ILPs (Non-CD47-Targeted Imiquimod-Encapsulated Liposomes), CLPs (CD47 Targeted Liposomes), and CILPs (Coupled Fc-CV1 to Imiquimod (TLR7 agonist)-Loaded Liposomes)
2.2. In Vitro Cell Uptake Efficiency
2.3. Release Curves of Liposomes
2.4. Cytotoxicity Study
2.5. Biodistribution Study
2.6. In Vivo Tumor Inhibition Study
2.7. CILPs Increased T-Cell Infiltration and Secretion of IFNγ
2.8. Biosecurity Assessment of CILPs
3. Materials and Methods
3.1. Materials
3.2. Preparation of Blank Liposomes
3.3. Preparation of CD47 Targeted Imiquimod-Encapsulated Liposomes
3.4. Characterization
3.5. In Vitro Cell Uptake Study
3.6. The Imiquimod Release Study
3.7. The Cytotoxicity of CILPs
3.8. Biodistribution Study
3.9. In Vivo Tumor Inhibition Study
3.10. Immunohistochemistry
3.11. Biosecurity Assessment of CILPs
3.12. Statistical Analysis
3.13. Animal Ethics
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Sample | Diameters (nm) | PDI | Zeta-Potential (mV) | EE (%) |
---|---|---|---|---|
LPs | 111.567 ± 0.655 | 0.095 ± 0.005 | −2.231 ± 0.167 | / |
CLPs | 117.467 ± 0.340 | 0.120 ± 0.018 | −2.492 ± 0.033 | / |
ILPs | 120.233 ± 0.776 | 0.125 ± 0.005 | −2.383 ± 0.070 | 81.205 ± 8.102 |
CILPs | 130.033 ± 0.974 | 0.144 ± 0.011 | −2.075 ± 0.070 | 85.443 ± 4.108 |
Group | Tumor Weight (g) | TGI |
---|---|---|
PBS | 1.246 ± 0.335 | \ |
LPs | 0.926 ± 0.150 | 28.319% |
imiquimod | 0.697 ± 0.212 | 44.061% |
Fc-CV1 | 0.799 ± 0.192 | 35.875% |
ILPs | 0.643 ± 0.282 | 48.395% |
CLPs | 0.846 ± 0.252 | 32.103% |
CILPs | 0.195 ± 0.054 | 84.350% |
Groups | ALT (10–96 U/L) | AST (36–235 U/L) | BUN (10–35 mg/dL) | CREA (11–85 umol/L) |
---|---|---|---|---|
PBS | 46.75 ± 1.75 | 262.42 ± 12.42 | 5.42 ± 0.42 | 51.34 ± 1.34 |
ILPs | 52.44 ± 2.44 | 209.58 ± 9.58 | 7.06 ± 1.06 | 46.10 ± 1.10 |
CLPs | 78.27 ± 3.27 | 208.49 ± 8.49 | 23.12 ± 3.12 | 39.57 ± 1.57 |
CILPs | 53.36 ± 3.36 | 232.91 ± 12.91 | 8.00 ± 1.00 | 44.87 ± 4.87 |
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Chang, R.; Chu, X.; Zhang, J.; Fu, R.; Feng, C.; Jia, D.; Wang, R.; Yan, H.; Li, G.; Li, J. Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPα Checkpoint Blockade for Efficient Treatment of Colon Cancer. Molecules 2023, 28, 3147. https://doi.org/10.3390/molecules28073147
Chang R, Chu X, Zhang J, Fu R, Feng C, Jia D, Wang R, Yan H, Li G, Li J. Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPα Checkpoint Blockade for Efficient Treatment of Colon Cancer. Molecules. 2023; 28(7):3147. https://doi.org/10.3390/molecules28073147
Chicago/Turabian StyleChang, Rui, Xiaohong Chu, Jibing Zhang, Rongrong Fu, Changshun Feng, Dianlong Jia, Rui Wang, Hui Yan, Guangyong Li, and Jun Li. 2023. "Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPα Checkpoint Blockade for Efficient Treatment of Colon Cancer" Molecules 28, no. 7: 3147. https://doi.org/10.3390/molecules28073147