title: Evaluation of new bi-functional terpolymeric nanoparticles for simultaneous in vivo optical imaging and chemotherapy of breast cancer.
abstract: Successful development of a nanoparticulate system for cancer chemotherapy requires detailed knowledge of its biodistribution, clearance and anti-tumour efficacy in vivo. Herein we developed new bi-functional nanoparticles for simultaneous in vivo optical imaging and delivery of the anticancer drug doxorubicin (Dox) for enhanced chemotherapy. Two types of nanoparticles were synthesized, namely preformed nanoparticles (PF-NPs) and self-assembled nanoparticles (SA-NPs). The PF-NPs were prepared by cross-linking graft polymerization of methacrylic acid and polysorbate 80 with starch (PMAA-PS 80-g-St) and then loading the particles with Dox. The SA-NPs were formed upon addition of Dox to non-cross-linked PMAA-PS 80-g-St. A near infrared fluorescent probe was conjugated with the PMAA unit of the nanoparticles. The biodistribution, tumour targeting and pharmacokinetics of the Dox-loaded nanoparticles in mice were determined by in vivo/ex vivo fluorescence imaging and ex vivo fluorescence microscopy. The anti-tumour efficacy of the nanoparticles was investigated using a murine orthotopic breast cancer model. PF-NPs had an average hydrodynamic diameter and zeta potential of 137 ± 3 nm and -38 ± 1 mV, respectively. These values were measured at 62 ± 5 nm and -35 ± 5 mV for SA-NPs. PF-NPs exhibited a porous morphology while the SA-NPs appeared to have a denser structure. SA-NPs outperformed the PF-NPs in terms of blood circulation, tumour uptake and penetration. PF-NPs and SA-NPs exhibited no systemic toxicity and inhibited tumour growth significantly better than the free Dox solution with SA-NPs being the best, attributable to their excellent tumour uptake and penetration. This work demonstrates the usefulness of these bi-functional nanoparticles as nanotheranostics.
authors: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada, M5S 3M2.
authors: Alireza
authors: A
authors: Shalviri
authors: Ping
authors: P
authors: Cai
authors: Andrew M
authors: AM
authors: Rauth
authors: Jeffery T
authors: JT
authors: Henderson
authors: Xiao Yu
authors: XY
authors: Wu