Jason McCarthy, PhD
Instructor in Chemistry, Harvard Medical School Phone: 617-726-9218 Email: jason_mccarthy@hms.harvard.edu The research of the McCarthy Group is focused on the synthesis of multimodal nanoparticle platforms for the diagnosis and treatment of diseases, such as atherosclerosis and cancer. The combination of light-activated photodynamic therapy (PDT) agents with fluorescent and/or magnetic resonance imaging modalities on a particulate scaffold yields nanoagents with properties that may prove advantageous in the clinical setting. PDT is the combination of a drug and light to yield a desired response. In the case of cancer, this means the eradication of tumor tissues. The main advantage of PDT is that the treatment is localized, which spares the surrounding healthy tissues. The main disadvantage is the extraneous photosensitivity caused by non-specific localization of the photosensitizer within the epidermis. To overcome this issue, we have encapsulated a potent chlorin-based photosensitizer within poly(lactic-co-glycolic acid) nanoparticles. While encapsulated, the sensitizer aggregates, which quenches the phototoxicity of the agent. When the particles are taken up by cells, the photosensitizer is released and regains its phototoxicity. This strategy has proven efficacious in vivo, as preliminary results in a murine model of cancer show complete eradication of tumors. We have also conjugated a photosensitizer to a magnetofluorescent nanoparticle for the treatment of atherosclerosis. Many prevalent diseases, such as atherosclerosis, have prominent inflammatory components that could be efficiently treated by localized, macrophage targeted therapies. We therefore synthesized a novel biocompatible nanoparticle with high avidity for macrophages, which encompasses magnetic (MRI detection) and fluorescent imaging (750 nm), as well as therapeutic functionalities, through a chlorin-based photosensitizer. We have demonstrated multimodal detection and exquisite phototoxicity to macrophages when illuminated by appropriate light. This multimodality, multispectral nanoparticle illustrates a new class of therapeutic drugs for the photo-activated treatment (photoangioplasty) of atherosclerosis, and offers diagnostic imaging capabilities as well as improved safety and targeting profiles. Publications Multifunctional magnetic nanoparticles for targeted imaging and therapy.
Adv Drug Deliv Rev. 2008;60:1241-1251
Model Systems for Fluorescence and Singlet Oxygen Quenching by Metalloporphyrins.
ChemMedChem. 2007;2:360-365
Targeted delivery of multifunctional magnetic nanoparticles
NanoMedicine. 2007;2(2):153-167
Novel Peptide Sequence ("IQ-tag") with High Affinity for NIR Fluorochromes Allows Protein and Cell Specific Labeling for In Vivo Imaging.
PLoS ONE. 2007;2:e665
A Macrophage Targeted Theranostic Nanoparticle for Biomedical Applications
Small. 2006;2(8-9):983-987
Conjugation of a Photosensitizer to an Oligoarginine-based Cell-penetrating Peptide Increases the Efficacy of Photodynamic Therapy
ChemMedChem. 2006;1(4):458-463
Polymeric Nanoparticle Preparation that Eradicates Tumors.
Nano Lett. 2005;5:2552-6
Crystal and molecular structure of [5,10,15,20-tetrakisphenyl-2-ethoxy-3-oxa-chlorinato]Ag(II).
J Chem Cristallogr. 2005;35(12):935-42
Synthesis of indaphyrins: meso-tetraarylsecochlorin-based porphyrinoids containing direct o-phenyl-to-beta-linkages.
Org Biomol Chem. 2004;2(10):1484-91
Indaphyrin, a meso-tetraphenylsecochlorin-derived chromophore incorporating o-phenyl-to-β-linkages
Chem Commun. 2003;:1738-9
Free base meso-tetraaryl-morpholinochlorins and porpholactone from meso-tetraaryl-2,3-dihydroxy-chlorin.
Org Lett. 2003;5(1):19-22
Use of Ag(II) as a removable ion in porphyrin chemistry: Diol cleavage products of [meso-tetraphenyl-2,3-diolchlorinato]Ag(II)
Tetrahedron. 2003;59:9137-46
A spectroscopic and computational study of the singlet and triplet excited states of synthetic beta-functionalized chlorins
Chem Phys. 2003;294:285-303
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