Paclitaxel-loaded PEGylated nanocapsules of perfluorooctyl bromide as theranostic agents.
We optimize the encapsulation of paclitaxel (PTX) into nanocapsules made of a shell of poly(lactide-co-glycolide)-polyethylene glycol and a core of perfluorooctyl bromide (PFOB) to serve as theranostic agents. Two main challenges were met: keeping the imaging moiety (PFOB) encapsulated while loading the polymer shell with a hydrophobic drug very prone to crystallization. Encapsulation is performed by a modified emulsion-evaporation method leading to 120nm diameter nanocapsules with a drug loading compatible with tumor treatment. The optimized formulation tested in vitro on CT-26 colon cancer cells yields a similar IC50 as the generic Taxol® formulation. In vivo,19F-MRI shows that PTX encapsulation does not modify the ability of nanocapsules to accumulate passively in CT-26 tumors in mice by the enhanced permeation and retention (EPR) effect. This accumulation leads to a promising and statistically significant twofold reduction in tumor growth as compared with negative control and generic Taxol® group. Altogether these results advocate for an interesting potential of these paclitaxel-loaded theranostic agents.
Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Tanguy
T
Boissenot
Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Elias
E
Fattal
Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Alexandre
A
Bordat
Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Sophie
S
Houvenagel
Commissariat à l'Energie Atomique (CEA), Institut d'Imagerie Biomédicale (I(2)BM), Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France.
Julien
J
Valette
Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Hélène
H
Chacun
Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Claire
C
Gueutin
Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
Nicolas
N
Tsapis
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy; D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D020128:Inhibitory Concentration 50; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D053769:Nanocapsules / Q000737:chemistry*; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D000068936:Theranostic Nanomedicine
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D053769:Nanocapsules; D011092:Polyethylene Glycols; D017239:Paclitaxel; C003072:perflubron
(19)F-MRI; Nanocapsules; Paclitaxel; Theranostics