808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd3+-sensitized upconversion emission with enhanced anti-tumor efficacy

Zhiyao Hou, Kerong Deng, Chunxia Li, Xiaoran Deng, Hongzhou Lian, Ziyong Cheng, Dayong Jin, Jun Lin*

*Corresponding author for this work

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYF4:Yb/Tm@NaYF4:Yb@NaNdF4:Yb@NaYF4 (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiO2, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiO2 shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd3+-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual-photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT.

Original languageEnglish
Pages (from-to)32-46
Number of pages15
JournalBiomaterials
Volume101
DOIs
Publication statusPublished - Sep 2016
Externally publishedYes

Keywords

  • Photodynamic therapy
  • 808 nm light
  • Hyaluronic acid target
  • Nd³⁺-sensitized upconversion nanoparticles
  • Dual-photosensitizers nanoplatform

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