Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer

Tzu-Yin Lin, Yuanpei Li, Qiangqiang Liu, Jui Lin Chen, Hongyong Zhang, Diana Lac, Hua Zhang, Katherine W. Ferrara, Sebastian Wachsmann-Hogiu, Tianhong Li, Susan Airhart, Ralph W deVere White, Kit Lam, Chong-Xian Pan

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)339-351
Number of pages13
JournalBiomaterials
Volume104
DOIs
StatePublished - Oct 1 2016

Fingerprint

Urinary Bladder Neoplasms
Doxorubicin
Photodynamic therapy
Chemotherapy
Photochemotherapy
Fluorescence
Cells
Aminolevulinic Acid
Bioelectric potentials
Therapeutics
Heterografts
Medicine
Tumors
Reactive Oxygen Species
Lighting
Ligands
Infrared radiation
Drug Therapy
Precision Medicine
Oxygen

Keywords

  • Bladder cancer
  • Nanotechnology
  • Photodynamic therapy
  • Photothermal therapy

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer. / Lin, Tzu-Yin; Li, Yuanpei; Liu, Qiangqiang; Chen, Jui Lin; Zhang, Hongyong; Lac, Diana; Zhang, Hua; Ferrara, Katherine W.; Wachsmann-Hogiu, Sebastian; Li, Tianhong; Airhart, Susan; deVere White, Ralph W; Lam, Kit; Pan, Chong-Xian.

In: Biomaterials, Vol. 104, 01.10.2016, p. 339-351.

Research output: Contribution to journalArticle

Lin, Tzu-Yin ; Li, Yuanpei ; Liu, Qiangqiang ; Chen, Jui Lin ; Zhang, Hongyong ; Lac, Diana ; Zhang, Hua ; Ferrara, Katherine W. ; Wachsmann-Hogiu, Sebastian ; Li, Tianhong ; Airhart, Susan ; deVere White, Ralph W ; Lam, Kit ; Pan, Chong-Xian. / Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer. In: Biomaterials. 2016 ; Vol. 104. pp. 339-351.
@article{ba9ccde182e6409ea0ecd42a5acd2712,
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.",
keywords = "Bladder cancer, Nanotechnology, Photodynamic therapy, Photothermal therapy",
author = "Tzu-Yin Lin and Yuanpei Li and Qiangqiang Liu and Chen, {Jui Lin} and Hongyong Zhang and Diana Lac and Hua Zhang and Ferrara, {Katherine W.} and Sebastian Wachsmann-Hogiu and Tianhong Li and Susan Airhart and {deVere White}, {Ralph W} and Kit Lam and Chong-Xian Pan",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.biomaterials.2016.07.026",
language = "English (US)",
volume = "104",
pages = "339--351",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer

AU - Lin, Tzu-Yin

AU - Li, Yuanpei

AU - Liu, Qiangqiang

AU - Chen, Jui Lin

AU - Zhang, Hongyong

AU - Lac, Diana

AU - Zhang, Hua

AU - Ferrara, Katherine W.

AU - Wachsmann-Hogiu, Sebastian

AU - Li, Tianhong

AU - Airhart, Susan

AU - deVere White, Ralph W

AU - Lam, Kit

AU - Pan, Chong-Xian

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

KW - Bladder cancer

KW - Nanotechnology

KW - Photodynamic therapy

KW - Photothermal therapy

UR - http://www.scopus.com/inward/record.url?scp=84979747678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979747678&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2016.07.026

DO - 10.1016/j.biomaterials.2016.07.026

M3 - Article

VL - 104

SP - 339

EP - 351

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -