#8. A Smaller Nanoparticle Assembly that Kills Tumor by Heat
NIH Title: Assemblies of nanoparticles for targeted image-guided photothermal therapy
NIH Reference Number: E-158-2015
Executive Summary:
General Description:
Photothermal therapy has shown potential in cancer treatment because of its spatiotemporal selectivity and minimal invasiveness comparing to the current standard of care such as surgery, chemotherapy and radiotherapy. The gold nanoparticles can be designed to specifically target cancer cells. When excited by light in a certain wavelength range, the nanoparticles emit heat that kills proximate cancer cells.
Early clinical studies with 150nm sized polyethylene glycol (PEG) coated gold particles showed encouraging results; however, the large-sized nanoparticles showed slow excretion from the body and toxicity.
Researchers prepared smaller nanoparticles with a size of approximately 50 nm and were able to overcome these challenges. The vesicles have a strong absorbance in the range of 700-980 nm and exhibited high tumor accumulation. They are also biodegradable and rapidly cleared from the body.
Scientific Progress:
Researchers at NIH developed a new water-oil-water emulsion method to self-assemble nanostructures of amphiphilic nanocrystals using gold nanorods (AuNR) coated with mixed polymer brushes of PEG and poly(lactic-co-glycolic acid) (PLGA). This method can more precisely control the size of the vesicle to be around 50 nm. Standard MTT assays were used to evaluate the cell toxicity in vitro. In vivo photothermal therapy using athymic nude mice showed high tumor accumulation efficiency. In vivo infrared light fluorescence/photoacoustic imaging monitoring the animal post-photothermal treatment showed rapid clearance of the nanostructures from the body. The tumor growth was almost completely inhibited by near-infrared laser at 0.2W/cm2 for 5 min. This preliminary data suggested that these new nanorod structures are promising anti-tumor agents and have broad biomedical applications because of their highly versatile structure.
Future Direction:
Strengths:
Weaknesses:
Patent Status:
Filing in progress
Publications:
Rong P. et al, PMID: 26382146
Song J et al, PMID: 26332111
Inventor Bio:
Dr. Chen received his BS (1993) and MS (1996) in chemistry from Nanjing University. He then came to the United States, where he completed his PhD degree (1999) in 3 years at the University of Idaho, under the supervision of Prof. Chien M. Wai. He was involved in chelation chemistry of alpha-emitting radionuclides. He then moved to upstate New York and spent 16 months as a postdoc at Syracuse University working with Prof. Jon Zubieta, where he learned crystallography and coordination chemistry of technetium and rhenium. Although his second postdoc at the Washington University in St. Louis was short, he was profoundly influenced by his mentor, Prof. Michael J Welch, who is renowned for applying modern chemistry to the preparation of radiopharmaceuticals in medical imaging.
He joined the University of Southern California as an Assistant Professor in 2002. By working with Prof. Peter Conti and Prof. James Bading, he pioneered multimodality imaging of angiogenesis marker integrin αvβ3. In 2004, he moved to the Molecular Imaging Program at Stanford (MIPS) under the directorship of Prof. Sanjiv Sam Gambhir, and was promoted to Associate Professor in 2008. During his tenure at Stanford, he successfully translated 18F-labeled RGD peptide dimer into clinic for first-in-human imaging studies. In the summer of 2009, he joined the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) as a Senior Investigator and Lab Chief.
He expanded the original PET Radiochemistry Group into the Laboratory of Molecular Imaging and Nanomedicine (LOMIN). LOMIN has three sections: the Chemistry and Radiochemistry Section (CRS); the Biological Molecular Imaging Section (BMIS); and the Theranostic Nanomedicine Section (TNS). CRS has research interests in the development of novel methods for incorporating radionuclides and fluorophores into molecules for the study of biologically important processes. BMIS focuses on identifying disease-specific biomarkers; developing new molecular imaging probes through cellular and molecular-biology-oriented methods; applying molecular probes in multimodality imaging; and characterizing novel imaging and therapeutic agents, both in vitro and in vivo. TNS creates and applies nanobiomaterials and devices that can provide personalized diagnosis, imaging, and therapy.
Dr. Chen has published over 500 peer-reviewed papers (H-index: 88; total citations: > 28,000) and numerous books and book chapters. He sits on the editorial board of over 10 peer-reviewed journals and is the founding editor of journal “Theranostics” (http://www.thno.org/).
NIH Reference Number: E-158-2015
Executive Summary:
- Invention Type: Therapeutic/diagnostic
- Patent Status: Patent pending
- Link: https://www.ott.nih.gov/technology/E-158-2015
- NIH Institute or Center: National Institute of Biomedical Imaging and Bioengineering (NIBIB)
- Disease Focus: Cancer
- Basis of Invention: Nano sized rod structures assembled by gold nanoparticles coated with PEG and PLGA
- How it works: The nano sized rods can specifically accumulate in the region of a solid tumor. An infrared light excites the photosensitive agents in the nanorod structure, which then releases heat to kill cancer cells
- Lead Challenge Inventor: Xiaoyuan (Shawn) Chen (NIBIB)
- Inventors: Xiaoyuan (Shawn) Chen (NIBIB), Jibin Song (NIBIB)
- Development Stage: Preclinical in vitro data showed the characterization of nanoparticle, in vivo data in athymic mouse model demonstrated tumor specific accumulation and rapid clearance from the body
-
Novelty:
- Gold nanorod particles are smaller in size compared to the current gold particles in clinical photothermal treatment for cancer
- High tumor-specific accumulation
- Rapid clearance from circulation
- Clinical Applications:
- Photothermal therapy
- Anticancer drug delivery for combined chemo/photothermal therapy
- Photoacoustic imaging
- CT contrasting agent
- Contrast-enhanced optical coherence imaging
General Description:
Photothermal therapy has shown potential in cancer treatment because of its spatiotemporal selectivity and minimal invasiveness comparing to the current standard of care such as surgery, chemotherapy and radiotherapy. The gold nanoparticles can be designed to specifically target cancer cells. When excited by light in a certain wavelength range, the nanoparticles emit heat that kills proximate cancer cells.
Early clinical studies with 150nm sized polyethylene glycol (PEG) coated gold particles showed encouraging results; however, the large-sized nanoparticles showed slow excretion from the body and toxicity.
Researchers prepared smaller nanoparticles with a size of approximately 50 nm and were able to overcome these challenges. The vesicles have a strong absorbance in the range of 700-980 nm and exhibited high tumor accumulation. They are also biodegradable and rapidly cleared from the body.
Scientific Progress:
Researchers at NIH developed a new water-oil-water emulsion method to self-assemble nanostructures of amphiphilic nanocrystals using gold nanorods (AuNR) coated with mixed polymer brushes of PEG and poly(lactic-co-glycolic acid) (PLGA). This method can more precisely control the size of the vesicle to be around 50 nm. Standard MTT assays were used to evaluate the cell toxicity in vitro. In vivo photothermal therapy using athymic nude mice showed high tumor accumulation efficiency. In vivo infrared light fluorescence/photoacoustic imaging monitoring the animal post-photothermal treatment showed rapid clearance of the nanostructures from the body. The tumor growth was almost completely inhibited by near-infrared laser at 0.2W/cm2 for 5 min. This preliminary data suggested that these new nanorod structures are promising anti-tumor agents and have broad biomedical applications because of their highly versatile structure.
Future Direction:
- Control the size of the vesicle by adjusting the water-oil-water ratio and PEG/PLGA ratio
- Insert hydrophobic drugs or anti-tumor biomolecules into the cavity of vesicle for enhanced tumor killing effects
- Conjugation of vesicle with target ligands such as antibodies, small molecules, peptides, etc. for enhanced tumor targeting efficiency
Strengths:
- Good biodegradability and biocompatibility
- Fast tumor accumulation
- Rapid excretion from body
- No off-target cytotoxicity
- Broad application including both therapeutic and diagnostic for cancer and potentially other diseases
Weaknesses:
- Early stage
Patent Status:
Filing in progress
Publications:
Rong P. et al, PMID: 26382146
Song J et al, PMID: 26332111
Inventor Bio:
Dr. Chen received his BS (1993) and MS (1996) in chemistry from Nanjing University. He then came to the United States, where he completed his PhD degree (1999) in 3 years at the University of Idaho, under the supervision of Prof. Chien M. Wai. He was involved in chelation chemistry of alpha-emitting radionuclides. He then moved to upstate New York and spent 16 months as a postdoc at Syracuse University working with Prof. Jon Zubieta, where he learned crystallography and coordination chemistry of technetium and rhenium. Although his second postdoc at the Washington University in St. Louis was short, he was profoundly influenced by his mentor, Prof. Michael J Welch, who is renowned for applying modern chemistry to the preparation of radiopharmaceuticals in medical imaging.
He joined the University of Southern California as an Assistant Professor in 2002. By working with Prof. Peter Conti and Prof. James Bading, he pioneered multimodality imaging of angiogenesis marker integrin αvβ3. In 2004, he moved to the Molecular Imaging Program at Stanford (MIPS) under the directorship of Prof. Sanjiv Sam Gambhir, and was promoted to Associate Professor in 2008. During his tenure at Stanford, he successfully translated 18F-labeled RGD peptide dimer into clinic for first-in-human imaging studies. In the summer of 2009, he joined the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) as a Senior Investigator and Lab Chief.
He expanded the original PET Radiochemistry Group into the Laboratory of Molecular Imaging and Nanomedicine (LOMIN). LOMIN has three sections: the Chemistry and Radiochemistry Section (CRS); the Biological Molecular Imaging Section (BMIS); and the Theranostic Nanomedicine Section (TNS). CRS has research interests in the development of novel methods for incorporating radionuclides and fluorophores into molecules for the study of biologically important processes. BMIS focuses on identifying disease-specific biomarkers; developing new molecular imaging probes through cellular and molecular-biology-oriented methods; applying molecular probes in multimodality imaging; and characterizing novel imaging and therapeutic agents, both in vitro and in vivo. TNS creates and applies nanobiomaterials and devices that can provide personalized diagnosis, imaging, and therapy.
Dr. Chen has published over 500 peer-reviewed papers (H-index: 88; total citations: > 28,000) and numerous books and book chapters. He sits on the editorial board of over 10 peer-reviewed journals and is the founding editor of journal “Theranostics” (http://www.thno.org/).
