A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly...

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Main Authors: Rui Liao, Yuequan Wang, Ziqi Lin, Yuting Wang, Hongyuan Zhang, Qin Chen, Shenwu Zhang, Jin Sun, Zhonggui He, Cong Luo
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Acta Pharmaceutica Sinica B
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211383525001662
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author Rui Liao
Yuequan Wang
Ziqi Lin
Yuting Wang
Hongyuan Zhang
Qin Chen
Shenwu Zhang
Jin Sun
Zhonggui He
Cong Luo
author_facet Rui Liao
Yuequan Wang
Ziqi Lin
Yuting Wang
Hongyuan Zhang
Qin Chen
Shenwu Zhang
Jin Sun
Zhonggui He
Cong Luo
author_sort Rui Liao
collection DOAJ
description Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.
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institution Kabale University
issn 2211-3835
language English
publishDate 2025-06-01
publisher Elsevier
record_format Article
series Acta Pharmaceutica Sinica B
spelling doaj-art-e86d799b946149dba9414f32b597a9282025-08-20T03:27:02ZengElsevierActa Pharmaceutica Sinica B2211-38352025-06-011563273329010.1016/j.apsb.2025.03.029A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatmentRui Liao0Yuequan Wang1Ziqi Lin2Yuting Wang3Hongyuan Zhang4Qin Chen5Shenwu Zhang6Jin Sun7Zhonggui He8Cong Luo9Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, ChinaDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China; Corresponding author.Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.http://www.sciencedirect.com/science/article/pii/S2211383525001662Prostate cancer treatmentGossypolCabazitaxelChemotherapeutic enhancerPrecise dual-drug nanoassemblyTherapeutic window broadening
spellingShingle Rui Liao
Yuequan Wang
Ziqi Lin
Yuting Wang
Hongyuan Zhang
Qin Chen
Shenwu Zhang
Jin Sun
Zhonggui He
Cong Luo
A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment
Acta Pharmaceutica Sinica B
Prostate cancer treatment
Gossypol
Cabazitaxel
Chemotherapeutic enhancer
Precise dual-drug nanoassembly
Therapeutic window broadening
title A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment
title_full A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment
title_fullStr A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment
title_full_unstemmed A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment
title_short A chemotherapy nano-booster unlocks wider therapeutic window for prostate cancer treatment
title_sort chemotherapy nano booster unlocks wider therapeutic window for prostate cancer treatment
topic Prostate cancer treatment
Gossypol
Cabazitaxel
Chemotherapeutic enhancer
Precise dual-drug nanoassembly
Therapeutic window broadening
url http://www.sciencedirect.com/science/article/pii/S2211383525001662
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