Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles

Liqun Dai; Xiaoyang Zhang; Siming Zhou; Jie Li; Lili Pan; Chunyan Liao; Zhipeng Wang; Ying Chen; Guohua Shen; Lin Li; Rong Tian; Hongbao Sun; Zhenhua Liu; Shiyong Zhang; Haoxing Wu

doi:10.1039/d3tb02543h

Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles

Liqun Dai, Xiaoyang Zhang, Siming Zhou, Jie Li, Lili Pan, Chunyan Liao, Zhipeng Wang, Ying Chen, Guohua Shen, Lin Li, Rong Tian, Hongbao Sun, Zhenhua Liu, Shiyong Zhang, Haoxing Wu

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

1 Scopus citations

Abstract

Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC.

Original language	English (US)
Pages (from-to)	2324-2333
Number of pages	10
Journal	Journal of Materials Chemistry B
Volume	12
Issue number	9
DOIs	https://doi.org/10.1039/d3tb02543h
State	Published - Feb 1 2024
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
Biomedical Engineering
General Materials Science

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10.1039/d3tb02543h

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Dai, L., Zhang, X., Zhou, S., Li, J., Pan, L., Liao, C., Wang, Z., Chen, Y., Shen, G., Li, L., Tian, R., Sun, H., Liu, Z., Zhang, S., & Wu, H. (2024). Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles. Journal of Materials Chemistry B, 12(9), 2324-2333. https://doi.org/10.1039/d3tb02543h

@article{58a762575b1640edb46f0764eacd21a5,

title = "Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles",

abstract = "Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC.",

author = "Liqun Dai and Xiaoyang Zhang and Siming Zhou and Jie Li and Lili Pan and Chunyan Liao and Zhipeng Wang and Ying Chen and Guohua Shen and Lin Li and Rong Tian and Hongbao Sun and Zhenhua Liu and Shiyong Zhang and Haoxing Wu",

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doi = "10.1039/d3tb02543h",

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Dai, L, Zhang, X, Zhou, S, Li, J, Pan, L, Liao, C, Wang, Z, Chen, Y, Shen, G, Li, L, Tian, R, Sun, H, Liu, Z, Zhang, S & Wu, H 2024, 'Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles', Journal of Materials Chemistry B, vol. 12, no. 9, pp. 2324-2333. https://doi.org/10.1039/d3tb02543h

TY - JOUR

T1 - Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles

AU - Dai, Liqun

AU - Zhang, Xiaoyang

AU - Zhou, Siming

AU - Li, Jie

AU - Pan, Lili

AU - Liao, Chunyan

AU - Wang, Zhipeng

AU - Chen, Ying

AU - Shen, Guohua

AU - Li, Lin

AU - Tian, Rong

AU - Sun, Hongbao

AU - Liu, Zhenhua

AU - Zhang, Shiyong

AU - Wu, Haoxing

PY - 2024/2/1

Y1 - 2024/2/1

N2 - Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC.

AB - Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC.

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JO - Journal of Materials Chemistry B

JF - Journal of Materials Chemistry B

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ER -

Pretargeted radiotherapy and synergistic treatment of metastatic, castration-resistant prostate cancer using cross-linked, PSMA-targeted lipoic acid nanoparticles

Abstract

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