Rhein-PEG-nHA conjugate as a bone targeted drug delivery vehicle for enhanced cancer chemoradiotherapy

Bone-targeted therapies have been the choice of treatments for cancer metastases in bone to minimize skeletal morbidity and preserve patients' quality of life. Rhein is of particular interest due to its high bone affinity. Here we reported a novel Rhein- polyethylene glycol (PEG)-nano hydroxyap...

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Published in:Nanomedicine 2020-07, Vol.27, p.102196-102196, Article 102196
Main Authors: Yang, Xiuying, Zhai, Dongliang, Song, Jia, Qing, Rui, Wang, Bochu, Ji, Jingou, Chen, Xiaoliang, Hao, Shilei
Format: Article
Language:English
Subjects:
Bone metastases
Bone targeting
Chemo-radiation combined therapy
Hydroxyapatite
Rhein
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Summary:Bone-targeted therapies have been the choice of treatments for cancer metastases in bone to minimize skeletal morbidity and preserve patients' quality of life. Rhein is of particular interest due to its high bone affinity. Here we reported a novel Rhein- polyethylene glycol (PEG)-nano hydroxyapatite (nHA) conjugate to deliver doxorubicin (DOX) and Phosphorus-32 (32P) simultaneously for enhanced cancer chemo-radiotherapy. The synthetic Rhein-PEG-nHA conjugates were sphere in shape with an average diameter of ~120 nm. Their morphology, drug release and bone affinity were confirmed in vitro. The release profiles of DOX depend on pH condition, but 32P exhibited good stability. Rhein-PEG-nHA also showed high bone affinity in vivo, and the tumor volume decreased after the DOX@Rhein-PEG-nHA and 32P@Rhein-PEG-nHA treatments. Most importantly, the DOX/32P@Rhein-PEG-nHA showed the strongest inhibition on the growth of bone metastases of breast cancer. We revealed the potential of Rhein-PEG-nHA in combined chemo-radiation treatment for bone metastases of breast cancer. Bone metastases is a common clinical problem, and bone-targeting treatments is an efficient way to enhance the clinical efficacy of bone metastases. This manuscript reports a novel approach using Rhein- polyethylene glycol (PEG)-nano hydroxyapatite (nHA) conjugates to deliver doxorubicin (DOX) and Phosphorus-32 (32P) simultaneously for enhanced cancer chemo-radiotherapy. The DOX/32P @Rhein-PEG-nHA displayed strongest tumor growth inhibition in vivo, and the bone destruction was also reduced efficiently. [Display omitted]
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2020.102196