A novel class of photo-triggerable liposomes containing DPPC:DC(8,9)PC as vehicles for delivery of doxorubcin to cells.
Success of nanoparticle-mediated drug delivery is subject to development of optimal drug release strategies within defined space and time (triggered release). Recently, we reported a novel class of photo-triggerable liposomes prepared from dipalmitoyl phosphatidylcholine (DPPC) and photopolymerizable diacetylene phospholipid (DC(8),(9)PC), that efficiently released entrapped calcein (a water soluble fluorescent dye) upon UV (254nm) treatment. To develop these formulations for in vivo applications, we have examined phototriggering of these liposomes by visible light, and the effect of released anticancer drugs on cellular toxicity. Sonicated liposomes containing various ratios of DPPC:DC(8),(9)PC and 4mol% DSPE-PEG2000 were loaded with calcein (Ex/Em, 485/517nm) or a chemotherapy drug, Doxorubicin (DOX, Ex/Em 490/590nm). Our initial experiments showed that 514nm laser treatment of liposomes containing 10 or 20mol% DC(8,9)PC for 1-3min resulted in significant release of calcein. Based on these results, we performed studies with DOX-loaded liposomes. First, biophysical properties (including liposome size and stability) and DOX encapsulation efficiency of the liposomes were determined. Subsequently, the effect of 514nm laser on DOX release, and cellular toxicity by released DOX were examined. Since liposomes using the 86:10:04 mole ratio of DPPC:DC(8),(9)PC:DSPE-PEG2000, showed highest encapsulation of DOX, these formulations were investigated further. We report that (i) liposomes retained about 70% of entrapped DOX at 37°C in the presence of 0-50% serum. (ii) 514nm laser treatment resulted in DOX release from liposomes in a wavelength-specific manner. (iii) Laser treatment of co-cultures containing DOX-loaded liposomes and cells (Raji and MCF-7) resulted in at least 2-3 fold improved cell killing as compared to untreated samples. Taken together, the photo-triggerable liposomes described here may provide a platform for future drug delivery applications. To our knowledge, this is the first report demonstrating improved cell killing following light-triggered release of an encapsulated anticancer agent from photosensitive liposomes.
Yavlovich
Amichai
A
Membrane Structure and Function Section, Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA.
Singh
Alok
A
Blumenthal
Robert
R
Puri
Anu
A
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001703:Biophysics / Q000379:methods; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007834:Lasers; D008027:Light; D008081:Liposomes / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D004317:Doxorubicin