Sequential Protein-Responsive Nanophotosensitizer Complex for Enhancing Tumor-Specific Therapy

Xingshu Li, Huanhuan Fan, Tian Guo, Huarong Bai, Nahyun Kwon, Kwang H. Kim, Sungsook Yu, Yejin Cho, Hyunji Kim, Ki Taek Nam, Juyoung Yoon, Xiao Bing Zhang, Weihong Tan

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9 Citations (Scopus)

Abstract

A major challenge in cancer treatment is the development of effective tumor-specific therapeutic methods that have minimal side effects. Recently, a photodynamic therapy (PDT) technique using activatable photosensitizers (aPSs) has shown great potential for cancer-specific treatment. Here, we develop a sequential protein-responsive aPS (PcC4-MSN-O1) that is based on zinc(II) phthalocyanine derivative (PcC4)-entrapped mesoporous silica nanoparticles (MSNs) and a wrapping DNA (O1) as a biogate. Inside the nanostructure of PcC4-MSN-O1, PcC4 shows self-quenching photoactivity. However, when PcC4-MSN-O1 sequentially reacts with telomerase and albumin, its photoactivity is dramatically turned on. Therefore, PcC4-MSN-O1 displays selective phototoxicity against cancer cells (e.g., HeLa) over normal cells (e.g., HEK-293). Following systemic PcC4-MSN-O1 administration, there is an obvious accumulation in HeLa tumors of xenograft-bearing mice, and laser irradiation clearly induces the inhibition of tumor growth. Moreover, the time-modulated activation process in tumors and the relatively fast excretion of PcC4-MSN-O1 indicate its advantages in reducing potential side effects.

Original languageEnglish
Pages (from-to)6702-6710
Number of pages9
JournalACS Nano
Volume13
Issue number6
DOIs
Publication statusPublished - 2019 Jun 25

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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    Li, X., Fan, H., Guo, T., Bai, H., Kwon, N., Kim, K. H., Yu, S., Cho, Y., Kim, H., Nam, K. T., Yoon, J., Zhang, X. B., & Tan, W. (2019). Sequential Protein-Responsive Nanophotosensitizer Complex for Enhancing Tumor-Specific Therapy. ACS Nano, 13(6), 6702-6710. https://doi.org/10.1021/acsnano.9b01100