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

Abstract
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.
AuthorsXiuying Yang, Dongliang Zhai, Jia Song, Rui Qing, Bochu Wang, Jingou Ji, Xiaoliang Chen, Shilei Hao
JournalNanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 27 Pg. 102196 (07 2020) ISSN: 1549-9642 [Electronic] United States
PMID32272233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020 Elsevier Inc. All rights reserved.
Chemical References
  • Anthraquinones
  • Immunoconjugates
  • Phosphorus Radioisotopes
  • Polyethylene Glycols
  • Phosphorus-32
  • Doxorubicin
  • Durapatite
  • rhein
Topics
  • Animals
  • Anthraquinones (chemistry, pharmacology)
  • Bone Neoplasms (drug therapy, pathology, radiotherapy, secondary)
  • Breast Neoplasms (drug therapy, pathology, radiotherapy)
  • Cell Line, Tumor
  • Doxorubicin (chemistry, pharmacology)
  • Drug Delivery Systems
  • Durapatite (chemistry, pharmacology)
  • Female
  • Humans
  • Immunoconjugates (chemistry, pharmacology)
  • Mice
  • Neoplasm Metastasis
  • Phosphorus Radioisotopes (chemistry, pharmacology)
  • Polyethylene Glycols (chemistry)
  • Xenograft Model Antitumor Assays

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