Improved Efficacy of Localized Brain Tumor Therapy using Photosensitive Nanoparticles.

Abstract

Currently, surgical resection serves as the leading management for the treatment of brain tumors. Performing a maximal resection must be balanced with the need to preserve adjacent non-cancerous brain tissue, and even with the best microsurgical technique, resection may leave behind residual tumor tissue. In order to provide a better approach to treat cancer patients, a minimally invasive localized treatment, photodynamic therapy (PDT), has been utilized to specifically treat localized and superficial tumors. PDT uses exogenously administered photosensitizers, such as Methylene Blue and HPPH, which are activated by a specific wavelength of light. The sensitizer, in its excited state, transfers its energy to molecular oxygen, forming reactive oxygen species which irreversibly oxidize essential cellular components, resulting in injury and necrosis of nearby tumor tissue. Photosensitizer-conjugated polyacrylamide nanoparticles were prepared for in vivo characterization of the minimally invasive and localized treatment of photodynamic therapy on brain tumors. PDT efficiency was improved by incorporating a variety of nanoparticle matrixes, photosensitizers, and targeting methods as well as exploring the systemic incubation of nanoparticles and fluence dependence on tumor response. Advancements and considerable attention to nanoparticle characteristics, incubation time, and photosensitizer delivery are proving allowance for further PDT quantification. Tumor growth patterns and tumorigenic response to various treatments were determined via visual observation by the use of an animal cranial window model. PDT treatments with photosensitizer loaded polyacrylamide nanoparticles, both with F3-targeting and PEG, displayed worthy homing and passive targeting efficiency towards the implanted 9L glioma, as shown by the significant phototoxic effect, killing the tumor cells in the treatment area of the cranial window. These photoreactive nanoparticles produced significant adjournment of tumor growth over control groups, clearly demonstrating the advantages of nanoparticle-based PDT agents. The advancements in therapy efficacy described in this thesis, has the potential to be utilized as an aid to neurosurgery for the eradication of local tumors, leading to the potential palliation of the advancing disease. This form of treatment can be extended to many other types of tumors to complement surgery or even by itself for small tumors.