Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456, Singapore.
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583, Singapore.
Adv Mater. 2020 Jul;32(29):e2001459. doi: 10.1002/adma.202001459. Epub 2020 Jun 2.
Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery.
近红外（NIR）激活上转换纳米粒子（UCNPs）通过将深部组织穿透的 NIR 转换为可见光，实现了基于无线的光疗。因此，UCNPs 是深部肿瘤光动力治疗（PDT）的理想无线换能器。然而，未被隔离的 UCNPs 在组织中的保留，且去除选择有限，限制了它们的临床转化。为了解决这一缺点，开发了生物相容性的 UCNPs 植入物，以在灵活的光导设计中提供上转换光子特性。为了提高其可转化性，UCNPs 植入物由经过 FDA 批准的聚乙二醇二丙烯酸酯（PEGDA）核和氟化乙烯丙烯（FEP）组成。UCNPs 植入物的发射光谱可以被调谐以与临床相关的光敏剂 5-氨基乙酰丙酸（5-ALA）的吸收光谱重叠。UCNPs 植入物可以以无线方式传输上转换的可见光，长度可达 8 厘米，甚至在皮肤或头皮下植入时也可以弯曲。通过该系统，证明了在无束缚和非侵入性的情况下，在小鼠异种移植胶质母细胞瘤多形性（GBM）模型中，可以实现基于 NIR 的慢性 PDT。据推测，这种封装的 UCNPs 植入物通过不影响无线深部组织光输送来隔离 UCNPs，代表了无线深部组织光疗的转化转变。
