Spatiotemporal controlled delivery of nanoparticles to injured vasculature.
There are a number of challenges associated with designing nanoparticles for medical applications. We define two challenges here: (i) conventional targeting against up-regulated cell surface antigens is limited by heterogeneity in expression, and (ii) previous studies suggest that the optimal size of nanoparticles designed for systemic delivery is approximately 50-150 nm, yet this size range confers a high surface area-to-volume ratio, which results in fast diffusive drug release. Here, we achieve spatial control by biopanning a phage library to discover materials that target abundant vascular antigens exposed in disease. Next, we achieve temporal control by designing 60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core, which is loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis and drug release over approximately 12 days. The nanoparticles inhibited human aortic smooth muscle cell proliferation in vitro and showed greater in vivo vascular retention during percutaneous angioplasty over nontargeted controls. This nanoparticle technology may potentially be used toward the treatment of injured vasculature, a clinical problem of primary importance.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Juliana M
JM
Chan
Liangfang
L
Zhang
Rong
R
Tong
Debuyati
D
Ghosh
Weiwei
W
Gao
Grace
G
Liao
Kai P
KP
Yuet
David
D
Gray
June-Wha
JW
Rhee
Jianjun
J
Cheng
Gershon
G
Golomb
Peter
P
Libby
Robert
R
Langer
Omid C
OC
Farokhzad
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D001698:Biomedical Engineering; D001808:Blood Vessels / Q000187:drug effects* / Q000293:injuries*; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage; D019151:Peptide Library; D051381:Rats; D017207:Rats, Sprague-Dawley
D000941:Antigens; D003692:Delayed-Action Preparations; D019151:Peptide Library; D017239:Paclitaxel