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. Effective.pdf
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