NIR Photoregulated Theranostic System Based on Hexagonal-Phase Upconverting Nanoparticles for Tumor-Targeted Photodynamic Therapy and Fluorescence Imaging

Abstract

Although photodynamic therapy (PDT) is an effective, minimally invasive therapeutic modality with advantages in highly localized and specific tumor treatments, large and deep-seated cancers within the body cannot be successfully treated due to low transparency to visible light. To improve the therapeutic efficiency of tumor treatment in deep tissue and reduce the side effects in normal tissue, this study developed a near-infrared (NIR)-triggered upconversion nanoparticle (UCNP)-based photosensitizer (PS) carrier as a new theranostics system. The NaYF4:Yb/Er UCNPs were synthesized by a hydrothermal method, producing nanoparticles of a uniformly small size (≈20 nm) and crystalline morphology of the hexagonal phase. These UCNPs were modified with folic acid-conjugated biocompatible block copolymers through a bidentate dihydrolipoic acid linker. The polymer modified hexagonal phase UCNPs (FA-PEAH-UCNPs) showed an improved dispersibility in the aqueous solution and strong NIR-to-vis upconversion fluorescence. The hydrophobic PS, pheophorbide a (Pha), was then conjugated to the stable vectors. Moreover, these UCNP-based Pha carriers containing tumor targeting folic acid ligands exhibited the significantly enhanced cellular uptake efficiency as well as PDT treatment efficiency. These results suggested that this system could extend the excitation wavelength of PDT to the NIR region and effectively improve therapeutic efficiency of PSs.

Tumor-responsive nanomedicine based on Ce3+-modulated up-/downconversion dual-mode emission for NIR-II imaging-guided dynamic therapy

“…As recognized, hexagonal LDNPs are outstanding NIR-to-visible or NIRto-UV nanotransducers so they were able to produce efficient photon upconversion. 56,57 Importantly, the diffraction peaks of pure hexagonal NaGdF 4 still existed in the XRD patterns of LDNPs@mSiO 2 , and LDNPs@CMSNs, which indicated LDNPs had relatively excellent physical and chemical stability as well as unchanged high purity of hexagonal NaGdF 4 . To identify the functional groups on the surface of materials, Fourier transforms infrared (FT-IR) spectroscopy was sufficiently used, which provided additional confirmation for successful preparation.…”

Recent advances in near infrared upconverting nanomaterials for targeted photodynamic therapy of cancer

“…121 A c c e p t e d M a n u s c r i p t Zhao et al developed UCNPs with folic acid-polyethylene glycol-poly(aspartic acid-hydrazone)dihydrolipoic acid (FA-PEAH) polymer chains conjugated to the surface. 133 Further functionalisation with pheophorbide a (Pha) as a PS drug via an acid-labile hydrazone linker allowed for pH-responsive release of the Pha within the lysosomal compartments of the cells.…”

“…The FA-PEAH-UCNPs-Pha showed also an enhanced PDT effect compared to the PEAH-UCNPs-Pha confirming the targeting ability of the nanosystem. 133 Another example of UCNPs functionalised with FA for targeted PDT was developed by Lim et al in which TCPP was used as PS drug. 134 Core-shell UCNPs were coated with silica and further functionalised via APTED addition with TCPP-NHS, PEG-NHS, and FA/PEG-NHS.…”

Non-Oncologic Applications of Nanomedicine-Based Phototherapy

“…The NIR light irradiation enhanced tissue penetration than visible light with reduced phototoxicity and background autofluorescence [ 93 ]. Therefore, UCNP-based PS was applied to the phototherapy to increase therapeutic efficacy [ 94 ]. Another recent study used the conjugation of UCNP with dual PSs (chlorin e6 and Rose Bengal) for greater ROS generation than single PS-based PDT [ 95 ].…”