title: Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer.
abstract: The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23 nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic.
authors.affiliation: Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA. Electronic address: tylin@ucdavis.edu.
authors.forename: Tzu-Yin
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Yuanpei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, Taipei 403, Taiwan.
authors.forename: Jui-Lin
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Lac
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
authors.affiliation: Department of Pathology and Laboratory Medicine and Center for Biophotonics Science and Technology, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wachsmann-Hogiu
authors.affiliation: Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA; VA Northern California Health Care System, Mather, CA 95655, USA.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Li
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Airhart
authors.affiliation: Department of Urology, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: deVere White
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.affiliation: Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA; VA Northern California Health Care System, Mather, CA 95655, USA; Department of Urology, University of California Davis, Sacramento, CA 95817, USA. Electronic address: cxpan@ucdavis.edu.
authors.forename: Chong-Xian
authors.initials: CX
authors.lastname: Pan
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000008:administration & dosage; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D010789:Phototherapy / Q000379:methods; D011166:Porphyrins / Q000008:administration & dosage*; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: C558117:PLZ4 peptide; D010456:Peptides, Cyclic; D017319:Photosensitizing Agents; D011166:Porphyrins; D004317:Doxorubicin
keywords: Bladder cancer; Nanotechnology; Photodynamic therapy; Photothermal therapy