Abstract
Most anticancer drugs are not able to cross the blood-brain barrier (BBB) effectively while surgery and radiation therapy cannot eradicate brain glioma cells and glioma stem cells (GSCs), hence resulting in poor prognosis with high recurrence rates. In the present study, a kind of multifunctional targeting daunorubicin plus quinacrine liposomes was developed for treating brain glioma and GSCs. Evaluations were performed on in-vitro BBB model, murine glioma cells, GSCs, and GSCs bearing mice. Results showed that the multifunctional targeting daunorubicin plus quinacrine liposomes exhibited evident capabilities in crossing the BBB, in killing glioma cells and GSCs and in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced efficacy of the multifunctional targeting drugs-loaded liposomes could be due to the following aspects: evading the rapid elimination from blood circulation; crossing the BBB effectively; improving drug uptake by glioma cells and GSCs; down-regulating the overexpressed ABC transporters; inducing apoptosis of GSCs via up-regulating apoptotic receptor/ligand (Fas/Fasl), activating apoptotic enzymes (caspases 8, 9 and 3), activating pro-apoptotic proteins (Bax and Bok), activating tumor suppressor protein (P53) and suppressing anti-apoptotic proteins (Bcl-2 and Mcl-1). In conclusion, the multifunctional targeting daunorubicin plus quinacrine liposomes could be used as a potential therapy for treating brain glioma and GSCs.
Highlights
Malignant brain glioma is the most lethal and aggressive type of cancer in oncology with a median survival of only 14.6 months and a 5-year survival rate of less than 5% [1, 2]
Results demonstrated that the multifunctional targeting liposomes were round shaped with smooth surface
Results exhibited that the release rates of daunorubicin and quinacrine from these liposomes were less than 5% within the initial 4 h
Summary
Malignant brain glioma is the most lethal and aggressive type of cancer in oncology with a median survival of only 14.6 months and a 5-year survival rate of less than 5% [1, 2]. Treatment for brain glioma depends on the location, the cell type and the grade of malignancy. Treatment is a combined approach, using surgery, radiation therapy and chemotherapy. The prognosis for patients is generally poor due to its pathological features. Most anticancer drugs are not able to cross the blood–brain barrier (BBB) effectively [3]. Surgery and radiation therapy cannot eradicate brain glioma cells and glioma stem cells (GSCs), leading to high recurrence rates. There is an urgent need for developing a new chemotherapy strategy to overcome the limitations
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