Effects of Phospholipid Structure on the Acoustic Cavitation of Functionalized Mesoporous Silica Nanoparticles: Implications for Image-Guided Drug Delivery

This study investigates the acoustic response of phospholipid-coated, hydrophobically modified mesoporous silica nanoparticles (PL-HMSNs) for image-guided drug delivery. PL-HMSNs were first stabilized with a PEGylated lipid, DSPE-PEG2k-methoxy, and the effect of particle concentration on the high-intensity focused ultrasound-induced cavitation threshold was explored. We found that increasing the particle concentration from 0 to 200 μg/mL decreased the acoustic pressure threshold for cavitation from ∼14 to ∼11 MPa, depending on the formulation. Dipalmitoylphosphatidylcholine (DPPC)-, distearoylphosphatidylcholine (DSPC)-, 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC)-, and 1,2-dibehenoyl- sn -glycero-3-phosphocholine (DBPC)-HMSNs gave similar cavitation thresholds. Dilauroylphosphatidylcholine (DLPC)-stabilized particles showed little to no cavitation, which was attributed to DLPC’s high critical micelle concentration. DOPC-HMSNs had a higher uptake into HTB-9 human urinary bladder cancer cells than DSPC HMSNs, which is consistent with liposome delivery reports using unsaturated lipids. Finally, the effect of mixed lipid tail lengths was investigated by combining fluid-forming DOPC with gel-forming lipids. Cavitation signal intensities for mixed lipid-stabilized HMSNswere significantly higher than those for pure lipids, which was ascribed to reduced line tension of mixed lipids. Our findings highlight that higher particle concentrations and longer lipid tail lengths can lower the cavitation threshold of PL-HMSNs, and combining saturated lipids with DOPC can amplify the cavitation response. These results provide insights for optimizing lipid-stabilized solid ultrasound contrast agents for drug delivery applications and show how common lipid formulations can be imparted with acoustic activity.