Macrophage-reprogramming upconverting nanoparticles for enhanced TAM-mediated antitumor therapy of hypoxic breast cancer
- Authors
- Yoon, Johyun; Le, Xuan Thien; Kim, Juho; Lee, Hyunjun; Nguyen, Nguyen Thi; Lee, Woo Tak; Lee, Eun Seong; Oh, Kyung Taek; Choi, Han-Gon; Youn, Yu Seok
- Issue Date
- Aug-2023
- Publisher
- Elsevier BV
- Keywords
- Cancer immunotherapy; M2-to-M1 repolarization; Photodynamic therapy; Tumor-associated macrophage; Upconversion nanoparticles
- Citation
- Journal of Controlled Release, v.360, pp 482 - 495
- Pages
- 14
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Controlled Release
- Volume
- 360
- Start Page
- 482
- End Page
- 495
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/113613
- DOI
- 10.1016/j.jconrel.2023.07.009
- ISSN
- 0168-3659
1873-4995
- Abstract
- In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated mannose-decorated/macrophage membrane–coated, silica-layered NaErF4@NaLuF4 upconverting nanoparticles (UCNPs) co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6) and loaded with paclitaxel (PTX) (UCNP@mSiO2-PFC/Ce6@RAW-Man/PTX: ∼61 nm; −11.6 mV). These nanoparticles were designed to have two major functionalities, (i) efficient singlet oxygen generation aided by an oxygen supply and (ii) good targeting to tumor-associated macrophage (TAMs) (M2-type), to induce polarization to M1 type macrophages that release proinflammatory cytokines and suppress breast cancers. The primary UCNPs consisted of lanthanide elements (erbium and lutetium) in a core@shell structure, and they facilely emitted 660 nm light in response to a deep-penetrating 808 nm near-infrared laser. Moreover, the UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX were able to release O2 and generate 1O2 because of the co-doped PFC/Ce6 and upconversion. Our nanocarriers' excellent uptake to RAW 264.7 macrophage cells (M2 type) and efficient M1-type polarization activity were clearly demonstrated using qRT-PCR and immunofluorescence-based confocal laser scanning microscopy. Our nanocarriers displayed significant cytotoxicity to 4T1 cells in 2D culture and 3D co-culture systems of 4T1/RAW 264.7 cells. More importantly, UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX (+808 nm laser) noticeably suppressed tumor growth in 4T1-xenografted mice, compared with the other treatment groups (332.4 vs. 709.5–1185.5 mm3). We attribute this antitumor efficacy to the prominent M1-type macrophage polarization caused by our nanocarriers through efficient ROS/O2 generation and targeting of M2-type TAMs via mannose ligands on coated macrophage-membrane. © 2023
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