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.