title: Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release.
abstract: Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Inclusion of 2 molar % porphyrin-phospholipid (PoP) imparted optimal near infrared (NIR) light-triggered release of doxorubicin (Dox) from conventional sterically stabilized stealth liposomes. The type and amount of PoP affected drug loading, serum stability and drug release induced by NIR light. Cholesterol and PEGylation were required for Dox loading, but slowed light-triggered release. Dox in stealth PoP liposomes had a long circulation half-life in mice of 21.9 h and was stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increased ∼ 7 fold in treated subcutaneous human pancreatic xenografts. Phototreatment induced mild tumor heating and complex tumor hemodynamics. A single chemophototherapy treatment with Dox-loaded stealth PoP liposomes (at 5-7 mg/kg Dox) eradicated tumors while corresponding chemo- or photodynamic therapies were ineffective. A low dose 3 mg/kg Dox phototreatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). To our knowledge, Dox-loaded stealth PoP liposomes represent the first reported long-circulating nanoparticle capable of light-triggered drug release.
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Dandan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Carter
authors.affiliation: Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, L8S4L8, Canada.
authors.forename: Aida
authors.initials: A
authors.lastname: Razi
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Jumin
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Giraldo
authors.affiliation: Department of Biomedical, Industrial & Human Factors Engineering, Wright State University, Dayton, OH 45435, USA.
authors.forename: Ulas
authors.initials: U
authors.lastname: Sunar
authors.affiliation: Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, L8S4L8, Canada.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Ortega
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA. Electronic address: jflovell@buffalo.edu.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D065546:Drug Liberation; D005260:Female; D006801:Humans; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000628:therapy; D010743:Phospholipids / Q000737:chemistry; D010789:Phototherapy; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry; D013696:Temperature
chemical_list: D010743:Phospholipids; D011166:Porphyrins; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol
keywords: Chemophototherapy; Chemotherapy; Doxorubicin; Liposomes; Phototherapy; Porphyrin-phospholipid