Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

摘要

An obstacle to successful cancer drug therapy is the existence of drug delivery barriers, which causes insufficient drug delivery to the tumor tissue. Because of the inadequate drug delivery, the drug dose has to be increased, which leads to normal tissue toxicity. This delivery problem not only limits the clinical application of existing chemotherapeutics, but also decreases the effectiveness of many new drugs under development for prostate cancer. We found that vascular targeting photodynamic therapy (PDT), a modality involving the combination of a photosensitizer and laser light, is able to disrupt tumor vascular barrier, a significant hindrance to drug delivery. Therefore, tumor accumulation of circulating molecules is significantly enhanced, which has been demonstrated by intravital fluorescence microscopy and whole-body fluorescence imaging techniques. Immunofluorescence staining of endothelial cytoskeleton structure further indicates microtubule depolymerization, stress actin fiber formation and intercellular gap formation. Based on these results, we are using this laser-based therapy to enhance anticancer drug effectiveness. PDT is currently in worldwide multicenter clinical trials for the localized prostate cancer therapy. The available results indicate that PDT employing advanced laser fiber technology and sophisticated light dosimetry is able to treat localized prostate cancer in an effective and safe way. The combination of photosensitization with current chemotherapy or other new drug therapies will further improve its treatment for the localized prostate cancer patients that accounts for more than 90% of total prostate cancer population.