SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy.

Autor: Kamarudin JBM; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597., Sun B; Department of Biomedical Engineering, College of Design & Engineering, National University of Singapore, Singapore, S117575., Foo ASC; Division of Neurosurgery, Department of Surgery, National University Hospital, National University Health System, Singapore, S119074., Lim XY; MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597., Judd H; Ngee Ann Polytechnic, Singapore, S599489., Tan X; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597., Tan XH; Department of Biomedical Engineering, College of Design & Engineering, National University of Singapore, Singapore, S117575., Razar RBBA; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597., Liu M; Department of Biomedical Engineering, College of Design & Engineering, National University of Singapore, Singapore, S117575., Zhong J; Department of Biomedical Engineering, College of Design & Engineering, National University of Singapore, Singapore, S117575., Chua JJE; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597.; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, S138673.; Neurobiology Program, Life Science Institute, National University of Singapore, Singapore, S117456., Ng CWQ; Division of General Surgery (Breast Surgery), Department of Surgery, National University Hospital, National University Health System, Singapore, S119074., Goh JCH; Department of Biomedical Engineering, College of Design & Engineering, National University of Singapore, Singapore, S117575., Tan TZ; Genomics and Data Analytics Core, Cancer Science Institute of Singapore, National University of Singapore, Singapore, S117599., Parikh BH; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, S138673., Su X; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, S138673.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597., Kumar AP; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597.; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597., Ong WY; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597.; Neurobiology Program, Life Science Institute, National University of Singapore, Singapore, S117456., Yamaguchi N; Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, 153-8904, Japan., Set SY; Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, 153-8904, Japan., Yip GW; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597., Zhang Y; Department of Biomedical Engineering, College of Design & Engineering, National University of Singapore, Singapore, S117575., Teh DBL; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597.; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597.; Neurobiology Program, Life Science Institute, National University of Singapore, Singapore, S117456.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, S117597.
Jazyk: angličtina
Zdroj: ACS nano [ACS Nano] 2023 Jun 27; Vol. 17 (12), pp. 11593-11606. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1021/acsnano.3c01916
Abstrakt: Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF 4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/ HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.
Databáze: MEDLINE