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 witha PEGylated lipid, DSPE-PEG2k-methoxy, and the effect of particleconcentration on the high-intensity focused ultrasound-induced cavitationthreshold was explored. We found that increasing the particle concentrationfrom 0 to 200 & mu;g/mL decreased the acoustic pressure thresholdfor cavitation from & SIM;14 to & SIM;11 MPa, depending on theformulation. 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, whichwas attributed to DLPC's high critical micelle concentration.DOPC-HMSNs had a higher uptake into HTB-9 human urinary bladder cancercells than DSPC HMSNs, which is consistent with liposome deliveryreports using unsaturated lipids. Finally, the effect of mixed lipidtail lengths was investigated by combining fluid-forming DOPC withgel-forming lipids. Cavitation signal intensities for mixed lipid-stabilizedHMSNswere significantly higher than those for pure lipids, which wasascribed to reduced line tension of mixed lipids. Our findings highlightthat higher particle concentrations and longer lipid tail lengthscan lower the cavitation threshold of PL-HMSNs, and combining saturatedlipids with DOPC can amplify the cavitation response. These resultsprovide insights for optimizing lipid-stabilized solid ultrasoundcontrast agents for drug delivery applications and show how commonlipid formulations can be imparted with acoustic activity.