Journal
BIOMATERIALS
Volume 278, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121135
Keywords
Photodynamic therapy (PDT); Photothermal therapy (PTT); Transcytosis; ROS-Responsive; Immunogenic cell death (ICD)
Funding
- National Science and Technology Major Special Project-Major New Drug Creation [2019ZX09301-112]
- Major Basic Research Projects of Shandong Natural Science Foundation, P.R.China [ZR2018ZC0232]
- Shandong Natural Science Foundation, P.R.China [ZR2020QH351]
- Shandong Provincial Program of Taishan Industrial Experts [2019TSCYCX-31]
- Fundamental Research Funds of Shandong University [2020GN091]
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The CPIM nanoplatform combines size-transforming and transcytosis strategies to enhance tumor penetration and drug delivery, resulting in significant effects on tumor penetration, drug transport, and anti-tumor immunity.
The restricted tumor penetration has been regarded as the Achilles' Heels of most nanomedicines, largely limiting their efficacy. To address this challenge, a cluster-bomb-like nanoplatform named CPIM is prepared, which for the first time combines size-transforming and transcytosis strategies, thus enhancing both passive and active transport. For passive diffusion, the cluster-bomb CPIM (135 nm) releases drug-loaded bomblets (IR780/1-methyl-tryptophan (1 MT) loaded PAMAM, <10 nm) in response to the high reactive-oxygen-species (ROS) concentration in tumor microenvironment (TME), which promotes intratumoral diffusion. Besides, IR780 generates ROS upon NIR irradiation and intensifies this responsiveness; therefore, there exists a NIR-triggered self-destructive behavior, rendering CPIM spatiotemporal controllability. For active transport, the nanoplatform is proven to be delivered via transcytosis with/without NIR irradiation. Regarding the anti-cancer performance, CPIM strengthens the photodynamic therapy (PDT)/photothermal therapy (PTT) activity of IR780 and IDO pathway inhibition effect of 1 MT, thus exhibiting a strongest inhibitory effect on primary tumor. CPIM also optimally induces immunogenic cell death, reverses the cold TME to a hot one and evokes systemic immune response, thus exerting an abscopal and anti-metastasis effects. In conclusion, this work provides a facile, simple yet effective strategy to enhance the tumor penetration, tumor-killing effect and antitumor immunity of nanomedicines.
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