Pegylated composite nanoparticles containing upconverting phosphors and meso-tetraphenyl porphine (TPP) for photodynamic therapy

Jingning Shan, Stephanie J. Budijono, Guohong Hu, Nan Yao, Yibin Kang, Yiguang Ju, Robert Krafft Prud'homme

Research output: Contribution to journalArticle

162 Scopus citations

Abstract

The utilization of upconverting nanophosphors (UCNP) for photodynamic therapy (PDT) has gained significant interests due to its ability to convert deep-penetrating near-infra red (NIR) light (i.e., 978 nm) to visible light. Previous attempts to co-localize UCNPs with photosensitizers suffer from low photosensitizer loading and problems with nanoparticle aggregation. Here, the preparation of a novel composite nanoparticle formulation comprising 100 nm β-NaYF4:Yb3+,Er3+ UCNPs, and meso-tetraphenyl porphine (TPP) photosensitizer, stabilized by biocompatible poly(ethylene glycol-block-(dl)lactic acid) block copolymers (PEG-b-PLA) is presented. A photosensitizer loading of 10 wt% with respect to UCNP crystal was achieved via the Flash NanoPrecipitation (FNP) process. A sterically stabilizing PEG layer on the composite nanoparticle surface prevents nanoparticle aggregation and ensures nanoparticle stability in water, PBS buffer, and culture medium containing serum proteins, resulting in nanoparticle suitable for in vivo applications. Based on in vitro studies utilizing HeLa cervical cancer cell lines, the composite nanoparticles are shown to exhibit low dark toxicity and efficient cancer cell-killing activity upon NIR excitation. Exposure with 134 W cm-2 of 978 nm light for 45 min resulted in 75% HeLa cell death. This is the first quantification of the cell-killing capabilities of the UCNP/TPP composite nanoparticles formulated for photodynamic therapy. A kinetically driven self-assembly process successfully produces poly(ethylene glycol)-stabilized composite nanoparticles, which simultaneously encapsulate upconverting phosphors and photosensitizers within the cores. These nanoparticles are capable of producing cytotoxic singlet oxygen upon near-infrared excitation and have potential applications in improved photodynamic cancer therapy, deep tissue imaging and biomarker identification.

Original languageEnglish (US)
Pages (from-to)2488-2495
Number of pages8
JournalAdvanced Functional Materials
Volume21
Issue number13
DOIs
StatePublished - Jul 8 2011

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

Keywords

  • block copolymers
  • nanoparticles.
  • photodynamic therapy
  • self-assembly
  • tetraphenyl porphines
  • upconverting nanophosphors

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