In order to improve the drug loading coefficient and realize the targeting delivey of paclitaxel (PTX) to brain and glioma,a novel core-shell structural phospholipid-functionalized mesoporous silica nanoparticles(MSN-LP) modified with Angiopep-2 (ANG-MSN-LP) were successfully developed using selfassembly and film hydration method,and mesoporous silica nanoparticles (MSN) synthesized by modified-Stober method also as control.By introducing the innovative preparation process of saturated solution adsorption method,PTX was highly encapsulated (drug loading efficiency up to 11.17%) into MSN (MSN-PTX) by forming crystal analogue complex inside the mesoporous pore channels.Results of in vitro release showed that about 75.5% of PTX released from ANG-MSN-LP-PTX (PTX loaded into ANG-MSN-LP) after 50 h and burst release was effectively reduced compared with MSN-PTX or PTX solution,indicating pronounced sustained-release characteristics.The biological safety of ANG-MSN-LP was evaluated by HBMEC and C6 cells,which proved ANG-MSN-LP has good biocompatibility and low toxicity.Compared to the control PTX formulations of MSN-PTX,MSN-LP-PTX (PTX loaded into MSN-LP) and PTX solution,ANG-MSN-LP-PTX were proved to increase the transport ratio of the PTX across the BBB and afterwards target the brain glioma and displayed higher cell uptake,stronger inhibition and apoptosis toward glioma cells,better glioma curing effect,and improved MST of C6 cells-implanted rats.Additionally,in pharmacokinetics by using blood and intracerebral microdialysis simultaneously,the AUC intracerebral of ANG-MSN-LP-PTX was increased to approximate 5.29-fold compared to that of PTX solution,but the AUCblood 2.85-fold.However,the most surprising is that the concentration-time curve of injected ANG-MSN-LP-PTX and MSN-LP-PTX tended to be similar to oral administration,which indicating that the nanoparticles as drug reservoirs can be detained in blood.In conclusion,ANG-MSN-LP are prospective targeting drug delivery system for therapy of brain glioma,Meanwhile,saturated solution adsorption method can increase the drug loading efficiency highly,blood and intracerebral microdialysis simultaneously can demonstrate the genuine capacity of brain targeting drug delivery system and precise pharmacokinetics of drug loaded in nanoparticles.