Objective The BTZ@PLGA-RGD nanoparticles that target integrin αvβ3 and are loaded with bortezomib （BTZ） were prepared to achieve targeted therapy for multiple myeloma （MM）. Methods The emulsion solvent evaporation method and carbodiimide chemistry method were used to form BTZ@PLGA-RGD nanoparticles. The characterization of BTZ@PLGA-RGD nanoparticles was confirmed with scanning electron microscopy （SEM）， dynamic light scattering （DLS）， and fourier-transform infrared （FTIR）. BTZ@PLGA-RGD nanoparticles were evaluated in terms of stability， encapsulation efficiency， release profile， and blood compatibility. The localization and cytotoxicity of BTZ@PLGA-RGD were determined using confocal laser scanning microscopy （CLSM） and the CCK-8 experiment. Results BTZ@PLGA-RGD nanoparticles were in a spherical shape with a uniform size distribution. The mean particle size of BTZ@PLGA-RGD nanoparticles was （113.7 ± 3.1） nm， accompanied by a positive surface charge of （+6.4 ± 1.3） mV. The entrapment efficiency of the BTZ@PLGA-RGD nanoparticles was 73.32%. These nanoparticles exhibited good long-term stability and blood compatibility. BTZ@PLGA-RGD nanoparticles had pH-responsive drug release properties， and the cumulative drug release （%） over 48 h was （82.34 ± 0.12）%. FTIR analysis indicated that BTZ was successfully loaded into the BTZ@PLGA-RGD nanoparticles， and RGD was successfully immobilized on the surface of the nanoparticles. The localization analysis showed that the active targeting effect mediated by the RGD peptide enabled the BTZ@PLGA - RGD nanoparticles to be taken up by RPMI8226 cells more efficiently， and these nanoparticles could achieve lysosome escape. The CCK-8 experimental results indicated that BTZ@PLGA-RGD nanoparticles exhibited stronger cytotoxicity against RPMI8226 cells. Conclusion BTZ@PLGA-RGD demonstrates outstanding stability， water solubility， targeting ability， controlled drug-release properties， and biological safety， offering a novel research strategy for MM targeted therapy.