Abstract: OBJECTIVE To prepare and evaluate Angiopep-2 (ANG) modifying neurotoxin (NT) loaded phospholipid-functionalized mesoporous silica nanoparticles (MSN) (ANG-LP-MSN-NT). METHODS MSN was synthesized by modified-Stober method. MSN-NT was developed by impregnation adsorption method. ANG-LP-MSN-NT was prepared by film hydration method. Laser particle size analyzer and transmission electron microscope were used to determine the particle size, Zeta potential and morphology. Small angle X-ray diffraction was used to determine the mesoporous structure; nitrogen adsorption method was used to calculate the surface area, pore diameter and pore volume. The drug release behavior of ANG-LP-MSN-NT was studied by dialysis method. Pharmacodynamics of ANG-LP-MSN-NT was studied by the hot-plate test and the acetic acid-writhing test. RESULTS The specific surface area, pore diameter and pore volume (V_p) of MSN were 557 m²·g^-1, 2.94 nm and 0.58 cm³·g^-1, respectively. The mean particle size and Zeta potential of ANG-LP-MSN-NT were (123.37±3.76)nm with PDI 0.20±0.02 and (-16.57±1.59)mV. The drug loading and entrapment efficiency of ANG-LP-MSN-NT were (10.75±0.54)% and (91.82±3.12)%. In vitro release, compared with MSN-NT, burst release of ANG-LP-MSN-NT was smaller and sustained release was more obvious. The results of pharmacodynamics experiment showed that the onset time and the maximum effect of ANG-LP-MSN-NT were better than other groups. CONCLUSION The successful preparation of ANG-LP-MSN-NT solves the problem of aggregation and burst release of MSN and low drug loading and easy leakage of liposomes. ANG-LP-MSN-NT has profit for NT enrichment in brain and a better analgesic effect. ANG-LP-MSN is a prospective drug delivery system for neurotoxin.