title: Surface modification of liposomes with rhodamine-123-conjugated polymer results in enhanced mitochondrial targeting.
abstract: A novel mitochondrial-targeted liposomal drug-delivery system was prepared by modification of the liposomal surface with a newly synthesized polymer, rhodamine-123 (Rh123)-PEG-DOPE inserted into the liposomal lipid bilayer. This novel polymer was synthesized by conjugating the mitochondriotropic dye Rh123, with the amphiphilic polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate. The modified liposomes showed better uptake by cells (HeLa, B16F10) estimated by fluorescence microscopy and FACS analysis. The co-localization study with stained mitochondria as well as with the isolation of mitochondria of the cultured cells after their treatment with Rh123 liposomes showed a high degree of accumulation of the modified liposomes in the mitochondria. We also prepared mitochondrial-targeted and nontargeted paclitaxel (PCL)-loaded liposomes. Mitochondrial-targeted PCL-loaded liposomes demonstrated enhanced cytotoxicity toward cancer cells compared with nontargeted drug-loaded liposomes or free PCL. Thus, Rh123-modified liposomes target mitochondria efficiently and can facilitate the delivery of a therapeutic payload to mitochondria.
authors.affiliation: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Biswas
authors.forename: Namita S
authors.initials: NS
authors.lastname: Dodwadkar
authors.forename: Rupa R
authors.initials: RR
authors.lastname: Sawant
authors.forename: Alexander
authors.initials: A
authors.lastname: Koshkaryev
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D020112:Rhodamine 123 / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D008081:Liposomes; D020112:Rhodamine 123