Low molecular weight heparin modified bone targeting liposomes for orthotopic osteosarcoma and breast cancer bone metastatic tumors

The standard-of-care chemotherapy is important in the treatment of osteosarcoma and bone metastastic tumors. However, the efficacy is limited by the specific physiological environment of the bone. Thus, developing an efficient antitumor and anti-metastasis chemotherapeutic formulation is desired for treatment of bone tumors. Herein, we utilized the alendronate (ALN) and low molecular weight heparin (LMWH) modified liposomes to deliver the antitumor drug doxorubicin (DOX), where traditionally-believed non-active drug carrier, targeting moiety could also exhibit biological functions and realize anti-tumor and anti-metastasis efficiency synergistically with the antitumor drug. Specifically, ALN could serve as the bone targeting moiety and the therapeutic agents of anti-osteoporosis. LMWH could enhance the blood circulation time of liposomes and exhibit anti-metastasis efficiency. Besides characterization of typical physiochemical properties of the delivery system, both the orthotopic osteosarcoma model and bone metastasis cancer model were adopted to evaluate the in vivo efficacy. The results proved this system could remarkably suppress tumor growth and inhibit tumor metastasis. (C) 2020 Published by Elsevier B.V.