Fluorophore labeling of core-crosslinked polymeric micelles for multimodal in vivo and ex vivo optical imaging.
OBJECTIVE
To enable multimodal in vivo and ex vivo optical imaging of the biodistribution and tumor accumulation of core-crosslinked polymeric micelles (CCPMs).


METHODS
mPEG-b-p(HPMAm-Lac)-based polymeric micelles, core-crosslinked via cystamine and covalently labeled with two different fluorophores (Dy-676/488), were synthesized. The CCPMs were intravenously injected into CT26 tumor-bearing mice.


RESULTS
Upon intravenous injection, the CCPMs accumulated in CT26 tumors reasonably efficiently, with values reaching approximately 4%ID at 24 h. Ex vivo two-photon laser scanning microscopy confirmed efficient extravasation of the image-guided CCPMs out of tumor blood vessels and relatively deep penetration into the tumor interstitium.


CONCLUSIONS
CCPMs were labeled with multiple fluorophores, and the results obtained exemplify that combining several different in vivo and ex vivo optical imaging techniques is highly useful for analyzing the biodistribution and tumor accumulation of nanomedicines.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
Yang
Y
Shi
Sijumon
S
Kunjachan
Zhuojun
Z
Wu
Felix
F
Gremse
Diana
D
Moeckel
Marc
M
van Zandvoort
Fabian
F
Kiessling
Gert
G
Storm
Cornelus F
CF
van Nostrum
Wim E
WE
Hennink
Twan
T
Lammers
D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D064847:Multimodal Imaging; D061848:Optical Imaging; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution
D000178:Acrylamides; D002232:Carbocyanines; C573549:DY-676; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007211:Indoles; D008823:Micelles; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C032976:N-(2-hydroxypropyl)methacrylamide
PEG; drug targeting; micelles; nanomedicine; optical imaging; pHPMA; theranostics