Targeted delivery of temozolomide to pediatric brain tumors using micelle-based theranostic nanocarriers

K. Miller, S. Dixit, A-L. Bredlau, A-M. Broome
Medical University of South Carolina, US

Keywords: diffuse pontine glioma, temozolomide, micelle, PDGFR

Summary:

Diffuse intrinsic pontine glioma (DIPG) is the single most devastating pediatric brain tumor. Surgical excision of these tumors, due to the exquisite location of the pons, is dangerous and is not curative. No chemotherapy has been identified that can control these tumors. One theory for this failure is that the pons is a unique location into which delivery of medications at therapeutic concentrations is singularly challenging. Current standard of care utilizes temozolomide (TMZ), a pro-drug that releases a DNA alkylating agent that is used to kill glial cells. TMZ is very toxic when delivered systemically and therapeutic dosages are limited by severe side effects. These factors necessitate a selectively targeted carrier for TMZ to deliver the drug efficiently to malignant cells avoiding nonspecific interaction and reducing offsite toxicity. In order to design an efficient and effective drug carrier, we addressed several issues: a tailored surface on the carrier to attach biomolecules for targeted drug delivery; a biocompatible coating which can efficiently encapsulate the hydrophobic drug thereby reducing cytotoxicity; and stimuli-induced (pH) disruption of the carrier agent for slow and controlled drug release to the desired environment.