nanoparticles for medical and surgical tumor therapy
DESCRIPTION
Nanoparticles for Medical and Surgical Tumor Therapy . James M. Provenzale, MD. Departments of Radiology, Oncology and Biomedical Engineering Emory University School of Medicine and Department of Radiology Duke University Medical Center. Disclosures. Bayer Pharmaceuticals Advisory Board. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/1.jpg)
Nanoparticles for Medical and Surgical Tumor Therapy
Departments of Radiology, Oncology and Biomedical EngineeringEmory University School of Medicine
and Department of Radiology
Duke University Medical Center
James M. Provenzale, MD
![Page 2: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/2.jpg)
Disclosures
• Bayer Pharmaceuticals Advisory Board
• Research Funding from Bayer Pharmaceuticals and GE Healthcare
![Page 3: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/3.jpg)
Aims
• Discuss medical uses of nanoparticles
• Show how nanoparticles and fluorescent molecules can be used for intraoperative imaging
![Page 4: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/4.jpg)
• Chemotherapy or radiation therapy
Delivery Vehicles
• Other therapeutic drugs
• Gene therapy
• Materials for tissue engineering
![Page 5: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/5.jpg)
• vesicles having a phospholipid bilayer membrane and an aqueous core
Liposomes
S. Leary. Neurosurgery 2006; 58:1009-1025
![Page 6: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/6.jpg)
Liposomes
• Some liposomal chemotherapy formulations are already in clinical use
• Liposomal doxorubicin for Kaposi’s sarcoma and ovarian cancer
• Opportunity exists for targeted delivery
![Page 7: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/7.jpg)
Targeted Imaging
tumor-targeted nanoparticles
C. Sun et al. Small 2008; 4:372-379
non-targeted nanoparticles
Subcutaneous implantation of glioma
![Page 8: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/8.jpg)
S. Leary. Neurosurgery 2006; 58:1009-1025
Multi-functional Capability
![Page 9: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/9.jpg)
Liposomes
• Can be made modified for delivery of contents solely at target-site
- disruption by ultrasound focused solely at the tumor
- disruption by heat applied at tumor site
- Responsive to local environmental conditions (e.g., pH, hypoxia)
![Page 10: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/10.jpg)
Tissue Regeneration
G Silva. Nat Rev Neurosci 2006; 7:65-74
VM Tysseling-Mattiace. J Neurosci 2008; 28:3814-
3823
![Page 11: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/11.jpg)
Multiple Sclerosis
Treatment: Decrease inflammatory response
Imaging: Targeting myelin debris
Nanoscaffold with axonal nutrients
![Page 12: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/12.jpg)
• Thermal ablation
Therapeutic Uses
• Intra-operative guidance for improving surgical margins
![Page 13: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/13.jpg)
E. Dickerson. Cancer Letters 2008; 269:57-66
Thermal Ablation
Control injection- saline, no
nanoparticles
Intravenous injection of gold nanoparticles
Intratumoral injection of gold nanoparticles
Mice bearing squamous cell carcinoma implants
![Page 14: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/14.jpg)
Thermal Ablation
Signal proportional to number of particles within tumor
Intravenous injection of gold nanoparticles
Intratumoral injection of gold nanoparticles
Control injection- no nanoparticles
![Page 15: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/15.jpg)
Thermal Ablation
Temperature change, 0 C Control injection,
no nanoparticles
Intratumoral injection of
gold nanoparticles
![Page 16: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/16.jpg)
Tumor Growth after Ablation
Intravenous injection of
nanoparticles
Control group- no nanoparticles
Intratumoral injection of
nanoparticles
![Page 17: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/17.jpg)
Findings after Thermal Ablation
L. Hirsch, et al. PNAS 2003; 100:13549-13554
Gross pathology
Silver staining for nanoparticles
Hematoxylin-eosin
![Page 18: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/18.jpg)
• Ultrasmall paramagnetic iron oxide particles that can be used for imaging
Iron Oxide Particles
JH Lee et al. Angew Chem Int Ed Engl 2006; 45:8160-8162
• Already in human use
![Page 19: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/19.jpg)
Intra-operative Imaging
Intra-operative 0.3T pre-resection
Intra-operative 0.3T post-resection
![Page 20: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/20.jpg)
Intraoperative Imaging
Problems:• High cost of MR scanners
• Usually not portable
• Increase surgical time
• Do not provide real-time feedback
![Page 21: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/21.jpg)
Real-time Intraoperative Imaging
• Fluorescent molecule as a contrast agent
• Laser excitation
• Passive accumulation in tumor hours after infusion
• Fluorescence depicted as color image or spectral wave form
![Page 22: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/22.jpg)
Real-time Intraoperative Imaging
![Page 23: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/23.jpg)
Improving Surgical Margins
• Subcutaneous breast cancer xenograft
• Resected tumor without optical imaging, to simulate conventional surgery
![Page 24: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/24.jpg)
Improving Surgical Margins• Tumor cells had
been modified to contain luciferase enzyme
• After injection of luciferin, tumor could be detected using bioluminescence imaging
![Page 25: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/25.jpg)
Positive Tumor Margin
![Page 26: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/26.jpg)
Improving Surgical Margins Optical Imaging
![Page 27: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/27.jpg)
Surgery in Large Animals Naturally occurring sarcoma in a dog
Resection 24 hours after infusion of fluorescent contrast agent
![Page 28: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/28.jpg)
Optical Imaging of Tumor
Regions of high signal intensity At histology, all sites were + for tumor
![Page 29: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/29.jpg)
Normal Tissue
Region of normal signal intensity
![Page 30: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/30.jpg)
Normal Tissue
Region of normal signal intensity
![Page 31: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/31.jpg)
Positive Tumor Margins
Region of high signal intensity
![Page 32: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/32.jpg)
Imaging-Histology Correlation• Canine patient with thyroid carcinoma
• Black- low signal (negative)
• Blue-intermediate signal (negative)
• Red- high signal (positive)
Imaging Histology
• Normal tissue- square
• Tumor- circle
![Page 33: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/33.jpg)
Imaging-Histology Correlation
• Black square- true negative
• Red circle- true positive
• Blue square- true negative
• Blue circle- false negative
![Page 34: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/34.jpg)
Imaging-Histology Correlation
• 4 true negatives
• 4 true positives
• 1 false negative
![Page 35: Nanoparticles for Medical and Surgical Tumor Therapy](https://reader035.vdocuments.net/reader035/viewer/2022062323/56816733550346895ddbe0ec/html5/thumbnails/35.jpg)
Summary
• Nanoparticles, alone or with fluorescent contrast agents, can provide a means to improve surgical results
• Nanoparticles have capabilities to delivery drug therapy and materials for tissue regeneration