Combination chemotherapeutic and immune-therapeutic anticancer approach via anti-PD-L1 antibody conjugated albumin nanoparticles
- Title
- Combination chemotherapeutic and immune-therapeutic anticancer approach via anti-PD-L1 antibody conjugated albumin nanoparticles
- Author
- 최한곤
- Keywords
- Chemo-immunotherapy; CTLA-4; Human serum albumin; Nanoparticle albumin-bound; Technology; PD-L1; pH-sensitive
- Issue Date
- 2021-11
- Publisher
- ELSEVIER
- Citation
- INTERNATIONAL JOURNAL OF PHARMACEUTICS, v. 605, Page. 2021-2033
- Abstract
- Anticancer regimens have been substantially enriched through monoclonal antibodies targeting immune
checkpoints, programmed cell death-1/programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte
antigen-4. Inconsistent clinical efficacy after solo immunotherapy may be compensated by nanotechnology-
driven combination therapy. We loaded human serum albumin (HSA) nanoparticles with paclitaxel (PTX) via
nanoparticle albumin-bound technology and pooled them with anti-PD-L1 monoclonal antibody through a pH-
sensitive linker for targeting and immune response activation. Our tests demonstrated satisfactory preparation
of paclitaxel-loaded, PD-L1-targeted albumin nanoparticles (PD-L1/PTX@HSA). They had small particle size
(~200 nm) and polydispersity index (~0.12) and successfully incorporated each constituent. Relative to normal
physiological pH, the formulation exhibited higher drug-release profiles favoring cancer cell-targeted release at
low pH. Modifying nanoparticles with programmed cell death-ligand 1 increased cancer cell internalization in
vitro and tumor accumulation in vivo in comparison with non-PD-L1-modified nanoparticles. PD-L1/PTX@HSA
constructed by nanoparticle albumin-bound technology displayed successful tumor inhibition efficacy both in
vitro and in vivo. There was successful effector T-cell infiltration, immunosuppressive programmed cell death-
ligand 1, and regulatory T-cell suppression because of cytotoxic T-lymphocyte antigen-4 synergy. Moreover,
PD-L1/PTX@HSA had low organ toxicity. Hence, the anti-tumor immune responses of PD-L1/PTX@HSA com-
bined with chemotherapy and cytotoxic T-lymphocyte antigen-4 is a potential anti-tumor strategy for improving
quantitative and qualitative clinical efficacy.
- URI
- https://www.sciencedirect.com/science/article/pii/S0378517321006219https://repository.hanyang.ac.kr/handle/20.500.11754/169834
- ISSN
- 0378-5173
- DOI
- 10.1016/j.ijpharm.2021.120816
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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