A Flexi‐PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy

Abstract

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.

Light Technology for Efficient and Effective Photodynamic Therapy: A Critical Review

“…Several light sources have been incorporated inside the implants to activate the PS, namely: (1) persistent luminescent materials (so-called “optical batteries”) such as nanoparticles (PLNPs) or green persistent luminescence materials (GPM), (2) UNCPs, and (3) micro-devices including LED sources and modules. For activation of the light sources, NIR radiation [ 236 , 237 , 238 ], radio-frequency (RF), near-field communication (NFC) [ 239 , 240 , 241 ], and ultrasound [ 242 ] have demonstrated their capabilities to activate the light sources.…”

“…Another NIR-activated implant relays on UCNPs (NaYF 4 :Yb 3+ , Er 3+ and NaYF 4 :Yb 3+ , Tm 3+ ) mixed with poly(ethylene glycol) diacrylate (PEGDA) and a fluorinated ethylene propylene (FEP) cladding layer to improve light transmission and minimize leakage of UCNPs [ 238 ]. The PS (5-ALA) is administrated systemically.…”

“…A brain tumour is studied, the results reveal beneficial outcomes and biocompatibility of the implant in comparison to interstitial fibre optics. Optical fibre produced higher glial scarring comprising both reactive microglia and astrocytes as compared to UCNPs implant [ 238 ]. Moreover, PDT-treated mice showed shrinkage of tumour size after 16 days, these results were confirmed by immunohistochemistry staining for the gross morphology of the engrafted tumour in brain slices.…”

Boosting the Energy Migration Upconversion through Inter-Shell Energy Transfer in Tb 3+ -Doped Sandwich Structured Nanocrystals

“…Nevertheless, the ultraviolet excitation of Tb 3+ complex inevitably causes the issues of poor tissue penetration of excitation light and background biofluorescence from endogenous chromophores and proteins for in vivo biodetection. [19][20][21][22][23][24][25][26] Unfortunately, even if substituting the luminescent Tb 3+ complex with the EMU NCs (e.g., NaGdF 4 :Yb/Tm@NaGdF 4 :Tb) that are excitable by 980 nm NIR light can help in the light penetration depth, [27][28][29][30] the issue of background biofluorescence induced by the ultraviolet upconversion emissions of Tm 3+ will still exist. This is because that the Tm 3+ ultraviolet emissions of considerable magnitude were always concomitant with the 5 D 4 → 7 F J emissions of Tb 3+ for the previously reported Tb 3+ -doped EMU NCs.…”

Biomedical Implants with Charge‐Transfer Monitoring and Regulating Abilities

“…Nevertheless, various de novo wireless implants have been designed, and studies on their clinical potential have been widely investigated by in vivo animal experiments. [ 21 ]…”