Photodynamic Molecular Beacons: An Image-Guided Therapeutic Approach to Breast Cancer Vertebral Metastases
Abstract
The vertebral column is the most common site of breast cancer metastases. Metastases disrupts the dynamic balance between bone resorption (by osteoclasts) and bone formation (by osteoblasts), inducing a vicious cycle whereby tumors reprogram osteoclasts causing osteolysis and promote tumor growth. The overexpression of MMPs in the vicious tumor-bone cycle not only aid tumors to spread to distant sites, but are also involved in the local dissolution of the vertebral body and tumor progression. Current therapies for managing vertebral metastases have significant limitations due to high associated risk of spinal cord damage. An attractive alternative is photodynamic therapy (PDT) for ablating breast cancer spinal metastases to relieve pain and prevent tumor progression and adjuvant to vertebroplasty, can stabilize weak and fractured vertebrae. However, current photosensitizers are limited by their non-specific accumulation. Photodynamic molecular beacons (PPMMPB), activated by MMPs, offer another level of PDT selectivity by preserving the spinal cord. Using a clinicallyrelevant metastatic model, PPMMPB-PDT results in the specific destruction of metastases while the spinal cord is left undamaged using a 150J light dose, a light dose 3 times greater than that achievable by the photosensitizer, Visudyne . PPMMPB-PDT appears to not only destroy metastatic tumours but also osteoclasts thereby disrupting the viscious tumour-bone osteolytic cycle increasing the success of vertebroplasty.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2012
- Accession Number
- ADA589200
Entities
People
- Tracy Liu
Organizations
- University Health Network