Alternating Magnetic Fields Trigger Apoptosis by Destruction of Lysosomes with LAMP1-Targeted Nanoparticles

Abstract

Magnetic nanoparticles (MNPs) can be shuffled into cells by external magnetic fields. The speed and frequency of MNP's movement in vivo can be modulated using alternating magnetic fields (AMF), which may provide the potential approach to selectively destroy cancer cells. To this end, 100nm MNPs conjugated with antibodies against LAMP1, a lysosomal transmembrane protein, were loaded into human endocrine pancreatic islet cells. MNPs were detected by live imaging and immunostaining, demonstrating that MNPs rapidly enter cells through the endocytic pathway and target the lysosomal membrane. The loading efficiency of LAMP1-MNPs was 21.2±2.4% which is significantly increased compared to non-targeted MNPs (13.3±2.3%). After treatment with AMF for 20 min at 40Hz, the lysosomal membrane was disrupted and early stage apoptosis of LAMP1-MNPs loaded cells significantly increased to 5.3±0.9% compared with 3.0±0.3% of MNPs (p<0.05). Cell proliferation was significantly decreased to 1.9∗10e5/ml from 3.2∗10e5/ml (p<0.01) in LAMP1-MNPs loaded cells from day 1 and onwards after 40Hz 20min of AMF. These results suggest that LAMP1-MNPs enter islet cells rapidly and preferentially locate to the lysosome. External AMF can kill the loaded cells by disrupting the lysosomal membrane.