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

doi:10.1021/acsnano.9b01100

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

BioMedical Science Institute

Research output: Contribution to journal › Article › peer-review

44 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 language	English
Pages (from-to)	6702-6710
Number of pages	9
Journal	ACS Nano
Volume	13
Issue number	6
DOIs	https://doi.org/10.1021/acsnano.9b01100
Publication status	Published - 2019 Jun 25

Bibliographical note

Funding Information:
X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002).

Funding Information:
X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002). J.Y. thanks the National Research Foundation of Korea (NRF), which was funded by the Korean government (MSIP) (Grant No. 2012R1A3A2048814). H.F. thanks the National Postdoctoral Program for Innovative Talents (BX201700072). K.T.N. thanks the Korea Mouse Phenotyping Project (NRF-2016M3A9D5A01952416) of the National Research Foundation.

Publisher Copyright:
© 2019 American Chemical Society.

All Science Journal Classification (ASJC) codes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsnano.9b01100

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title = "Sequential Protein-Responsive Nanophotosensitizer Complex for Enhancing Tumor-Specific Therapy",

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.",

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

note = "Funding Information: X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002). Funding Information: X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002). J.Y. thanks the National Research Foundation of Korea (NRF), which was funded by the Korean government (MSIP) (Grant No. 2012R1A3A2048814). H.F. thanks the National Postdoctoral Program for Innovative Talents (BX201700072). K.T.N. thanks the Korea Mouse Phenotyping Project (NRF-2016M3A9D5A01952416) of the National Research Foundation. Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

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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, Ki Taek

AU - Yoon, Juyoung

AU - Zhang, Xiao Bing

AU - Tan, Weihong

N1 - Funding Information: X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002). Funding Information: X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002). J.Y. thanks the National Research Foundation of Korea (NRF), which was funded by the Korean government (MSIP) (Grant No. 2012R1A3A2048814). H.F. thanks the National Postdoctoral Program for Innovative Talents (BX201700072). K.T.N. thanks the Korea Mouse Phenotyping Project (NRF-2016M3A9D5A01952416) of the National Research Foundation. Publisher Copyright: © 2019 American Chemical Society.

PY - 2019/6/25

Y1 - 2019/6/25

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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