Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy

Liqun Dai, Jie Liu, Tingyu Yang, Xiaorui Yu, Yi Lu, Lili Pan, Siming Zhou, Diyun Shu, Yuanhao Liu, Wuyu Mao () and Zhiyong Qian ()
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Liqun Dai: Sichuan University
Jie Liu: Sichuan University
Tingyu Yang: Sichuan University
Xiaorui Yu: Neuboron Medtech Ltd.
Yi Lu: Sichuan University
Lili Pan: Sichuan University
Siming Zhou: Sichuan University
Diyun Shu: Neuboron Medtech Ltd.
Yuanhao Liu: Neuboron Medtech Ltd.
Wuyu Mao: Sichuan University
Zhiyong Qian: Sichuan University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Cancer remains a major health challenge, with the effectiveness of chemotherapy often limited by its lack of specificity and systemic toxicity. Nanotechnology, particularly in targeted drug delivery, has emerged as a key innovation to address these limitations. This study introduces lipoic acid-boronophenylalanine (LA-BPA) derivatives that incorporate short-chain polyethylene glycol (PEG) as a spacer. These derivatives distinctively self-assemble into vesicles under specific pH conditions, exhibiting a pH-dependent reversible assembly characteristic. Notably, these vesicles target cancer cells by binding to sialic acid via phenylboronic acid groups, subsequently depleting cellular glutathione and elevating reactive oxygen species, thereby inducing apoptosis via mitochondrial dysfunction and mitophagy. The vesicles demonstrate high efficiency in encapsulating doxorubicin, featuring a glutathione-responsive release mechanism, which present a promising option for tumor therapy. Additionally, the derivatives of the B-10 isotope, containing up to 1.6% boron, are engineered for incorporation into LPB-3-based vesicles. This design facilitates their application in boron neutron capture therapy (BNCT) alongside chemotherapy for the treatment of pancreatic cancer. Our findings highlight the potential of LA-BPA derivatives in developing more precise, effective, and less detrimental chemoradiotherapy approaches, marking an advancement in nanomedicine for cancer treatment.

Date: 2025
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DOI: 10.1038/s41467-025-56507-4

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