Doxorubicin and mitomycin C co-loaded polymer-lipid hybrid nanoparticles inhibit growth of sensitive and multidrug resistant human mammary tumor xenografts.
Multidrug resistance (MDR) and drug toxicity are two major factors responsible for the failure of cancer chemotherapy. Herein the efficacy and safety of combination therapy using doxorubicin (Dox, D)-mitomycin C (MMC, M) co-loaded stealth polymer-lipid hybrid nanoparticles (DMsPLNs) were evaluated in sensitive and MDR human mammary tumor xenografts. DMsPLN demonstrated enhanced efficacy compared to liposomal Dox (PLD) with up to a 3-fold increase in animal life span, a 10-20% tumor cure rate, undetectable normal tissue toxicity and decreased tumor angiogenesis. These results suggest DMsPLN have potential as an effective treatment of breast cancer.
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, Canada M5S 3M2.
Preethy
P
Prasad
Adam
A
Shuhendler
Ping
P
Cai
Andrew M
AM
Rauth
Xiao Yu
XY
Wu
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004338:Drug Combinations; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011897:Random Allocation; D013228:Stearates / Q000008:administration & dosage / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D004338:Drug Combinations; D008055:Lipids; D013228:Stearates; D011092:Polyethylene Glycols; D016685:Mitomycin; D004317:Doxorubicin