Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U۸۷ cancer cells in ۳D culture model

Background and aim: Exosomes (EXOs) are naturally occurring nanosized lipid bilayers that can be efficiently used as a drug delivery system to carry small pharmaceutical, biological molecules and pass major biological barriers such as the blood-brain barrier. It was hypothesized that EXOs derived from human endometrial stem cells (hEnSCs-EXOs) can be utilized as a drug carrier to enhance tumor-targeting drugs, especially for those have low solubility and limited oral bioactivity.Materials and method: in this study, atorvastatin (Ato) loaded EXOs (AtoEXOs) was prepared and characterized for its physical and biological activities in tumor growth suppression of ۳ D glioblastoma model. The AtoEXOs were obtained in different methods to maximize drug encapsulation efficacy. The characterization of AtoEXOs was performed for its size, stability, drug release, and in vitro anti-tumor efficacy evaluated comprising inhibition of proliferation, apoptosis induction of tumor cells. Expression of apoptotic genes by Real time PCR, Annexin V/PI, tunnel assay was studied after ۷۲ h exposing U۸۷ cells where encapsulated in matrigel in different concentrations of AtoEXOs (۵, ۱۰ μM).Results: the results showed that the prepared AtoEXOs possessed diameter ranging from ۳۰–۱۵۰ nm, satisfying stability and sustainable Ato release rate. The AtoEXOs was up taken by U۸۷ and generated significant apoptotic effects while this inhibited tumor growth of U۸۷ cells.Conclusion: altogether, produced AtoEXOs formulation due to its therapeutic efficacy has the potential to be an adaptable approach to treat glioblastoma brain tumors.

Keywords:

Atorvastatin loaded exosome , Glioblastoma , Apoptotic effects , anti-Glioblastoma carrier