Abstract

Glioblastoma multiforme (GBM) is a fatal central nervous system tumor without effective treatment. Chemotherapeutic agents are mainstays in the treatment of glioblastoma. However, the effectiveness of these is seriously hindered by poor blood-brain-barrier (BBB) penetrance and tumor targeting, together with short biological half-life. Improved chemotherapy is thus urgently needed for GBM. Multifunctional nanoparticle delivery systems offer much promise in overcoming current limitations. Accordingly, we developed a multifunctional biomimetic nanomedicine by functionalizing the surface of red blood cell membranes (RBCms) with angiopep-2 and loading pH-sensitive nanoparticles (polymer, doxorubicin (Dox) and lexiscan (Lex)) using the functionalized cell membrane to generate the novel nanomedicine, Ang-RBCm@NM-(Dox/Lex). Our studies towards orthotopic U87MG human glioblastoma tumor-bearing nude mice showed that our Ang-RBCm@NM-(Dox/Lex) nanomedicine has much improved blood circulation time, superb BBB penetration, superior tumor accumulation and retention. Moreover, effective suppression of tumor growth and significantly improved medium survival time was also observed after Ang-RBCm@NM-(Dox/Lex) treatment. Our results show that this biomimetic nanoplatform can serve as a flexible and powerful system for GBM treatment which could be readily adapted for the treatment of other CNS disorders.