TY - JOUR
T1 - Near-infrared light-responsive liposomes for protein delivery
T2 - Towards bleeding-free photothermally-assisted thrombolysis
AU - Refaat, Ahmed
AU - del Rosal, Blanca
AU - Palasubramaniam, Jathushan
AU - Pietersz, Geoffrey
AU - Wang, Xiaowei
AU - Moulton, Simon E.
AU - Peter, Karlheinz
N1 - Funding Information:
A. R. acknowledges the financial support in the form of PhD Faculty Growth SUPRA scholarship jointly funded by Swinburne University of Technology and Baker Heart and Diabetes Institute . A. R. also thanks Faculty of Pharmacy- Alexandria University for their continued support. B. d. R. acknowledges funding from the Australian Research Council ( DE200100985 ) and RMIT University (VC Fellowships program). J.P. is supported by Monash University Scholarship and a National Health and Medical Research Council (NHRMC) Postgraduate Scholarship. X. W. is supported by a National Heart Foundation Future Leader Fellowship, Baker Fellowship , and K.P. is supported by an NHMRC Investigator Fellowship . S. E. M. acknowledges financial support from Swinburne University of Technology .
Funding Information:
A. R. acknowledges the financial support in the form of PhD Faculty Growth SUPRA scholarship jointly funded by Swinburne University of Technology and Baker Heart and Diabetes Institute. A. R. also thanks Faculty of Pharmacy- Alexandria University for their continued support. B. d. R. acknowledges funding from the Australian Research Council (DE200100985) and RMIT University (VC Fellowships program). J.P. is supported by Monash University Scholarship and a National Health and Medical Research Council (NHRMC) Postgraduate Scholarship. X. W. is supported by a National Heart Foundation Future Leader Fellowship, Baker Fellowship, and K.P. is supported by an NHMRC Investigator Fellowship. S. E. M. acknowledges financial support from Swinburne University of Technology. The authors acknowledge use of the RMIT Microscopy and Microanalysis Facility (RMMF) at RMIT University and thank Dr. Chaitali Dekiwadia for her technical assistance and helpful discussion.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9/10
Y1 - 2021/9/10
N2 - Smart drug delivery systems represent state-of-the-art approaches for targeted therapy of life-threatening diseases such as cancer and cardiovascular diseases. Stimuli-responsive on-demand release of therapeutic agents at the diseased site can significantly limit serious adverse effects. In this study, we engineered a near-infrared (NIR) light-responsive liposomal gold nanorod-containing platform for on-demand delivery of proteins using a hybrid formulation of ultrasmall gold nanorods (AuNRs), thermosensitive phospholipid (DPPC) and non-ionic surfactant (Brij58). In light-triggered release optimization studies, 55.6% (± 4.8) of a FITC-labelled model protein, ovalbumin (MW 45 kDa) was released in 15 min upon NIR irradiation (785 nm, 1.35 W/cm2 for 5 min). This platform was then utilized to test on-demand delivery of urokinase-plasminogen activator (uPA) for bleeding-free photothermally-assisted thrombolysis, where the photothermal effect of AuNRs would synergize with the released uPA in clot lysis. Urokinase light-responsive liposomes showed 80.7% (± 4.5) lysis of an in vitro halo-clot model in 30 min following NIR irradiation (785 nm, 1.35 W/cm2 for 5 min) compared to 36.3% (± 4.4) and 15.5% (± 5.5) clot lysis from equivalent free uPA and non-irradiated liposomes respectively. These results show the potential of low-dose, site-specific thrombolysis via the combination of light-triggered delivery/release of uPA from liposomes combined with photothermal thrombolytic effects from gold nanorods. In conclusion, newly engineered, gold nanorod-based, NIR light-responsive liposomes represent a promising drug delivery system for site-directed, photothermally-stimulated therapeutic protein release.
AB - Smart drug delivery systems represent state-of-the-art approaches for targeted therapy of life-threatening diseases such as cancer and cardiovascular diseases. Stimuli-responsive on-demand release of therapeutic agents at the diseased site can significantly limit serious adverse effects. In this study, we engineered a near-infrared (NIR) light-responsive liposomal gold nanorod-containing platform for on-demand delivery of proteins using a hybrid formulation of ultrasmall gold nanorods (AuNRs), thermosensitive phospholipid (DPPC) and non-ionic surfactant (Brij58). In light-triggered release optimization studies, 55.6% (± 4.8) of a FITC-labelled model protein, ovalbumin (MW 45 kDa) was released in 15 min upon NIR irradiation (785 nm, 1.35 W/cm2 for 5 min). This platform was then utilized to test on-demand delivery of urokinase-plasminogen activator (uPA) for bleeding-free photothermally-assisted thrombolysis, where the photothermal effect of AuNRs would synergize with the released uPA in clot lysis. Urokinase light-responsive liposomes showed 80.7% (± 4.5) lysis of an in vitro halo-clot model in 30 min following NIR irradiation (785 nm, 1.35 W/cm2 for 5 min) compared to 36.3% (± 4.4) and 15.5% (± 5.5) clot lysis from equivalent free uPA and non-irradiated liposomes respectively. These results show the potential of low-dose, site-specific thrombolysis via the combination of light-triggered delivery/release of uPA from liposomes combined with photothermal thrombolytic effects from gold nanorods. In conclusion, newly engineered, gold nanorod-based, NIR light-responsive liposomes represent a promising drug delivery system for site-directed, photothermally-stimulated therapeutic protein release.
KW - Drug release
KW - Gold nanorods
KW - Light-responsive liposomes
KW - Photothermally-assisted thrombolysis
KW - uPA
KW - Urokinase liposomes
UR - http://www.scopus.com/inward/record.url?scp=85111143292&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2021.07.024
DO - 10.1016/j.jconrel.2021.07.024
M3 - Article
C2 - 34284049
AN - SCOPUS:85111143292
SN - 0168-3659
VL - 337
SP - 212
EP - 223
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -
