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, KiTaek Nam, Juyoung Yoon, Xiao Bing Zhang, Weihong Tan

Research output: Contribution to journalArticle

1 Citation (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

Fingerprint

Silicon Dioxide
Tumors
therapy
tumors
Silica
Nanoparticles
silicon dioxide
proteins
Proteins
nanoparticles
cancer
Bearings (structural)
excretion
Photodynamic therapy
Photosensitizing Agents
Photosensitizers
Oncology
Telomerase
Laser beam effects
albumins

All Science Journal Classification (ASJC) codes

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

Cite this

Li, X., Fan, H., Guo, T., Bai, H., Kwon, N., Kim, K. H., ... 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
Li, Xingshu ; Fan, Huanhuan ; Guo, Tian ; Bai, Huarong ; Kwon, Nahyun ; Kim, Kwang H. ; Yu, Sungsook ; Cho, Yejin ; Kim, Hyunji ; Nam, KiTaek ; Yoon, Juyoung ; Zhang, Xiao Bing ; Tan, Weihong. / Sequential Protein-Responsive Nanophotosensitizer Complex for Enhancing Tumor-Specific Therapy. In: ACS Nano. 2019 ; Vol. 13, No. 6. pp. 6702-6710.
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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.",
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Li, X, Fan, H, Guo, T, Bai, H, Kwon, N, Kim, KH, Yu, S, Cho, Y, Kim, H, Nam, K, Yoon, J, Zhang, XB & Tan, W 2019, 'Sequential Protein-Responsive Nanophotosensitizer Complex for Enhancing Tumor-Specific Therapy', ACS Nano, vol. 13, no. 6, pp. 6702-6710. https://doi.org/10.1021/acsnano.9b01100

Sequential Protein-Responsive Nanophotosensitizer Complex for Enhancing Tumor-Specific Therapy. / Li, Xingshu; Fan, Huanhuan; Guo, Tian; Bai, Huarong; Kwon, Nahyun; Kim, Kwang H.; Yu, Sungsook; Cho, Yejin; Kim, Hyunji; Nam, KiTaek; Yoon, Juyoung; Zhang, Xiao Bing; Tan, Weihong.

In: ACS Nano, Vol. 13, No. 6, 25.06.2019, p. 6702-6710.

Research output: Contribution to journalArticle

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AU - Li, Xingshu

AU - Fan, Huanhuan

AU - Guo, Tian

AU - Bai, Huarong

AU - Kwon, Nahyun

AU - Kim, Kwang H.

AU - Yu, Sungsook

AU - Cho, Yejin

AU - Kim, Hyunji

AU - Nam, KiTaek

AU - Yoon, Juyoung

AU - Zhang, Xiao Bing

AU - Tan, Weihong

PY - 2019/6/25

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N2 - 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.

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