(704d) Composite up Converting Phosphor Nanoparticles for Photodynamic Therapy and Imaging

Authors: 
Prud'homme, R. K., Princeton University
Budijono, S. J., Princeton University
Ju, Y., Princeton University
Shan, J., Princeton University
Austin, R., Princeton University


Photodynamic therapy is an approved treatment for pulmonary and pleural mesothelial cancers. The therapy relies on cytotoxic singlet oxygen production due to excitation of a photosensitizer by a visible light. The current method has significant limitations firstly because many photosensitizers are hydrophobic and thus non-deliverable, the visible light used to excite these photosensitizers has a limited penetration distance in tissue and the mode of singlet oxygen delivery is not targeted specifically to cancer cells. We present a design of composite nanoparticles (CNPs) in which upconverting phosphors, a material capable of emitting visible light, are placed in close proximity to photosensitizer. The biocompatible, 140nm-phosphors, NaYF4:Yb3+,Er3+, produces green light upon excitation by infra red (980nm). The utilization of infra-red light in place of green laser light addresses penetration distance problem encountered in current PDT approach. The phosphors and the photosensitizer (meso-tetraphenyl porphine (mTPP)) are packaged in a single compartment using biocompatible, FDA-approved polymeric materials. Candidate block-copolymers include PEG-PCL (poly(ethylene glycol)-block-poly(caprolactone) and PEG-PLGA (poly(ethylene glycol)-block-poly(lactide-co-glycolide) acid). The CNPs are manufactured using Flash NanoPrecipitation technology which provides homogenous mixing, resulting in good control over nanoparticle size with high reproducibility. Our study suggests that PEG-PLGA provides better nanoparticle size control compared to PEG-PCL block-copolymers. The spherical composite nanoparticles of PEG-PLGA has a diameter of 200 nm while PEG-PCL 400 nm, both of which are stable in water. With a high ratio of photosensitizer to drug (1:3, by weight) in the composite, these CNPs are capable of producing cytotoxic singlet oxygen, as determined by ADPA tests. In vitro cell kill assays will be presented.