Porphyrin-phospholipid liposomes permeabilized by near-infrared light.
The delivery of therapeutic compounds to target tissues is a central challenge in treating disease. Externally controlled drug release systems hold potential to selectively enhance localized delivery. Here we describe liposomes doped with porphyrin-phospholipid that are permeabilized directly by near-infrared light. Molecular dynamics simulations identified a novel light-absorbing monomer esterified from clinically approved components predicted and experimentally demonstrated to give rise to a more stable porphyrin bilayer. Light-induced membrane permeabilization is enabled with liposomal inclusion of 10 molar % porphyrin-phospholipid and occurs in the absence of bulk or nanoscale heating. Liposomes reseal following laser exposure and permeability is modulated by varying porphyrin-phospholipid doping, irradiation intensity or irradiation duration. Porphyrin-phospholipid liposomes demonstrate spatial control of release of entrapped gentamicin and temporal control of release of entrapped fluorophores following intratumoral injection. Following systemic administration, laser irradiation enhances deposition of actively loaded doxorubicin in mouse xenografts, enabling an effective single-treatment antitumour therapy.
1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Kevin A
KA
Carter
1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Shuai
S
Shao
Department of Chemistry and Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Matthew I
MI
Hoopes
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Dandan
D
Luo
Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada L8S4L8.
Bilal
B
Ahsan
Department of Chemistry, University at Albany, State University of New York, Albany, New York 12222, USA.
Vladimir M
VM
Grigoryants
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Wentao
W
Song
1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Haoyuan
H
Huang
Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Guojian
G
Zhang
PDT Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Ravindra K
RK
Pandey
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Jumin
J
Geng
Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Blaine A
BA
Pfeifer
Department of Chemistry, University at Albany, State University of New York, Albany, New York 12222, USA.
Charles P
CP
Scholes
Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada L8S4L8.
Joaquin
J
Ortega
Department of Chemistry and Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Mikko
M
Karttunen
1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Jonathan F
JF
Lovell
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry / Q000528:radiation effects; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D005260:Female; D006801:Humans; D007259:Infrared Rays; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry* / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D010743:Phospholipids / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010743:Phospholipids; D011166:Porphyrins; D004317:Doxorubicin