Simultaneous delivery of doxorubicin and curcumin encapsulated in liposomes of pegylated RGDK-lipopeptide to tumor vasculature.
Curcumin, because of its distinguishing ability to inhibit activation of transcription factor linked to chemoresistance and drug transporters, is now being co-administered with various potent anti-cancer drugs. In the present study, we report on such potentiating capabilities of curcumin in anti-angiogenic cancer therapy. With a view to simultaneously deliver curcumin and doxorubicin to tumor vasculature in anti-angiogenic cancer therapy, herein we report on the design & synthesis of a tumor vasculature targeting pegylated RGDK-lipopeptide. We show that curcumin & doxorubicin co-encapsulated within the liposomes of the presently described pegylated RGDK-lipopeptide exhibit synergism in inhibiting proliferation, invasion and migration of both tumor and endothelial cells presumably by inhibiting proliferation and metastasis related genes both at mRNA & protein levels. Pronounced tumor growth inhibition was observed in mice treated with formulations containing both the drugs. Tumor growth inhibition was found to be 2-3 folds less in mice treated with formulations containing only curcumin or only doxorubicin. The presently described liposomal system is expected to find future use for simultaneously delivering potentially any combinations of hydrophilic and hydrophobic potent small molecule cancer therapeutics to tumor vasculature in anti-angiogenic cancer therapy.
Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Sugata
S
Barui
Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Soumen
S
Saha
Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Goutam
G
Mondal
Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Shaik
S
Haseena
Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: arabinda@iict.res.in.
Arabinda
A
Chaudhuri
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis; D002453:Cell Cycle; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D055666:Lipopeptides / Q000008:administration & dosage*; D008081:Liposomes; D051379:Mice; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000903:Antibiotics, Antineoplastic; D055666:Lipopeptides; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003474:Curcumin
Anti-angiogenic chemotherapy; Curcumin–doxorubicin synergy; Pegylated RGDK-lipopeptide; Targeting tumor vasculature; Tumor growth inhibition