In vitro evaluation of a biomaterial-based anticancer drug delivery system as an alternative to conventional post-surgery bone cancer treatment

Iris Bischoff, Roman Tsaryk, Feng Chai, Robert Fürst, Charles James Kirkpatrick, Ronald E. Unger

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Patients diagnosed with osteosarcoma are currently treated with intravenous injections of anticancer agents after tumor resection. However, due to remaining neoplastic cells at the site of tumor removal, cancer recurrence often occurs. Successful bone regeneration combined with the control of residual cancer cells presents a challenge for tissue engineering. Cyclodextrins loaded with chemotherapeutic drugs reversibly release the drugs over time. Hydroxyapatite bone biomaterials coated with doxorubicin-loaded cyclodextrin should release the drug with time after implantation directly at the original tumor site and may be a way to eliminate residual neoplastic cells. In the present study, we have carried out in vitro studies to evaluate such a drug-delivery system and have shown that doxorubicin released from cyclodextrin-coated hydroxyapatite retained biological activity and exhibited longer and higher cytotoxic effects on both cancer (osteosarcoma cells) and healthy cells (primary osteoblasts and endothelial cells) compared to biomaterials without cyclodextrin loaded with doxorubicin. Furthermore, doxorubicin released from biomaterials with cyclodextrin moderately induced the expression of tumor suppressor protein p53 whereas p21 expression was similar to control cells. In addition, hypoxic conditions, which occur after implantation until blood-flow to the area is regenerated, protected endothelial cells and primary osteoblasts from doxorubicin-induced cytotoxicity. This chemo-protective effect was far less prominent for the osteosarcoma cells. These findings indicate that a hydroxyapatite-cyclodextrin-doxorubicin chemotherapeutic strategy may enhance the drug-targeting effect on tumor cells while protecting the more sensitive healthy cells for a period of time after implantation. A successful integration of such a drug delivery system might allow healthy cells to initially survive during the doxorubicin exposure period, while eliminating residual neoplastic cells.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalMaterials Science and Engineering C
StatePublished - 1 Dec 2018
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a grant of the Federal Ministry of Education and Research (ERA Net EuroTransBio-4: AnCaBoR, Funding number: BMBF 0315771B ).

Publisher Copyright:
© 2018 Elsevier B.V.


  • Cancer cells
  • Doxorubicin
  • Drug-delivery
  • Healthy cells
  • Hypoxia
  • Polycyclodextrin hydroxyapatite


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