Lysyl oxidase-responsive anchoring nanoparticles for modulation of the tumor immune microenvironment
- Authors
- Park, Jinwon; Kim, Jung Suk; Yang, Geon; Lee, Hobin; Shim, Gayong; Lee, Jaiwoo; Oh, Yu Kyoung
- Issue Date
- Aug-2023
- Publisher
- ELSEVIER
- Keywords
- Lysyl oxidase; Extracellular matrix anchoring; Collagen coating; Tumor immune microenvironment; Immunotherapy
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.360, pp.376 - 391
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 360
- Start Page
- 376
- End Page
- 391
- URI
- http://scholarworks.bwise.kr/ssu/handle/2018.sw.ssu/44236
- DOI
- 10.1016/j.jconrel.2023.06.041
- ISSN
- 0168-3659
- Abstract
- In the tumor microenvironment, lysyl oxidase (LOX) is known to play a key role in stabilizing the tumor extracellular matrix. Here, we designed LOX-responsive nanoparticles to interact with the collagen matrix of the tumor microenvironment. Collagen-coated and imiquimod-loaded polydopamine nanoparticles (CPN/IQ) could form crosslinked structures with the collagen matrix via LOX. In vitro, anchoring of CPN/IQ nanoparticles was observed with LOX-secreting CT26 cells, but this was blocked by a LOX inhibitor. In CT26 tumor-bearing mice, co-administration of nanoparticles plus the LOX inhibitor did not significantly alter the antitumor efficacy among nanoparticles. In the absence of the LOX inhibitor, however, a single administration of CPN/IQ could provide sustained responsiveness to near-infrared irradiation and ablation of primary tumors. In the primary tumor microenvironment, CPN/IQ lowered the Treg cell population but increased the cytotoxic CD3+CD8+ T cell population. In splenic dendritic cells, CPN/IQ treatment significantly increased the CD11c+CD86+ and CD11c+CD80+ cell populations. In a CT26 distant tumor-rechallenge model, CPN/IQ treatment increased the cytotoxic CD3+CD8+ T cell population and provided 100% survival of mice until 64 days. This study indicates the feasibility of tumor immune microenvironment modulation using LOX-responsive size-transforming nanoparticles. Although we tested the concept in a CT26 cell-derived tumor model, the concept of LOX-responsive collagen matrix- anchoring nanoparticles may be broadly applied to other tumor tissues with LOX-rich tumor microenvironments.
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