Skip to Main content Skip to Navigation
Journal articles

2b80 − Hydroxybisphosphonate Linked Doxorubicin: Bone Targeted Strategy for Treatment of Osteosarcoma

Abstract : To reply to as yet unmet medical needs to treat osteosarcoma, a form of primary bone cancer, we conceived the 12b80 compound by covalently conjugating antineoplastic compound doxorubicin to a bone targeting hydroxybisphosphonate vector and turned it into a prodrug through a custom linker designed to specifically trigger doxorubicin release in acidic bone tumor microenvironment. Synthesis of 12b80 was thoroughly optimized to be produced at gram scale. 12b80 was evaluated in vitro for high bone support affinity, specific release of doxorubicin in acidic condition, lower cytotoxicity, and cellular uptake of the prodrug. In vivo in rodents, 12b80 displayed rapid and sustained targeting of bone tissue and tumor-associated heterotopic bone and permitted a higher doxorubicin payload in tumor bone environment compared to nonvectorized doxorubicin. Consequently, 12b80 showed much lower toxicity compared to doxorubicin, promoted strong antitumor effects on rodent orthotopic osteosarcoma, displayed a dose-response therapeutic effect, and was more potent than doxorubicin/zoledronate combination.
Complete list of metadatas

Cited literature [55 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02529711
Contributor : Dominique Heymann <>
Submitted on : Thursday, April 2, 2020 - 3:01:30 PM
Last modification on : Thursday, June 18, 2020 - 5:48:01 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Emmanuelle David, Sebastien Cagnol, Jean-Yves Goujon, Maxim Egorov, Julien Taurelle, et al.. 2b80 − Hydroxybisphosphonate Linked Doxorubicin: Bone Targeted Strategy for Treatment of Osteosarcoma. The Lancet Oncology, 2019, 20 (1), pp.12-14. ⟨10.1021/acs.bioconjchem.9b00210⟩. ⟨inserm-02529711⟩

Share

Metrics

Record views

61