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

Linlin Zhao,So Yeon Kim,Jongseon Choi,Yan Lu

doi:10.3390/nano10122332

Linlin Zhao, So Yeon Kim + Show 2 more

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https://doi.org/10.3390/nano10122332

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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.

Highlights

Photodynamic therapy (PDT) has been recognized as a promising treatment method for a variety of cancers due to its minimal normal tissue toxicity, little invasiveness, highly localized and specific tumor treatments, fewer adverse effects as compared with chemotherapy and radiation therapy [1,2,3,4]
The conjugation content of pheophorbide a (Pha) to folic acid-polyethylene glycol-poly(aspartic acid-hydrazone)-dihydrolipoic acid (FA-PEAH)-upconversion nanoparticle (UCNP) was determined by 1H NMR using the relative intensity ratio of the methylene protons of the PEG chain (-OCH2CH2, 3.5 ppm) to the methylene protons of Pha (8.9 ppm, 9.4 ppm, and 9.8 ppm)
The conjugation content of photosensitizer Pha in folic acid (FA)-PEAH-UCNPs-Pha carrier was determined as about 14.7%

Summary

Introduction

Photodynamic therapy (PDT) has been recognized as a promising treatment method for a variety of cancers due to its minimal normal tissue toxicity, little invasiveness, highly localized and specific tumor treatments, fewer adverse effects as compared with chemotherapy and radiation therapy [1,2,3,4]. Most clinically approved current PSs in PDT are hydrophobic and have limited solubility in aqueous solution These hydrophobic PSs can aggregate under physiological conditions, which can dramatically decrease the 1O2 quantum yield and eventually affect the therapeutic efficiency of PDT [9,10]. To address these issues, various nanocarriers such as micelles [11,12], liposomes [13], dendrimers [14], gold nanoparticles [15], mesoporous materials [16] and carbon nanotubes [17,18,19] have been investigated as for the delivery of PSs in cancer therapy

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