Ultrasound‐Triggered Destruction of Folate‐Functionalized Mesoporous Silica Nanoparticle‐Loaded Microbubble for Targeted Tumor Therapy

Abstract

A multifunctional drug delivery vehicle, which combines the active targeted mesoporous silica nanoparticle (MSN) and microbubble (MB) drug delivery system, is proposed and fabricated. The resulting delivery vehicle integrates the merits of high drug loading capacity, multitargeting, and ultrasound-guided releasing. Folate (FA), which serves as an active ligand, is modified to the surface of MSN (MSN-FA) to enhance cell membrane translocation. MSN-FA is loaded with tanshinone IIA (TAN), then encapsulated in a microbubble (denoted as MSN-FA-TAN-MB) for more precise tumor targeting. The conjunction between FA and MSN is confirmed by fourier transform infrared spectroscopy (FTIR). The characteristics and morphology of MSN-FA-TAN-MB are investigated by confocal microscopy and transmission electron microscopy. In vitro cytotoxicity and cellular uptake studies of MSN-FA-TAN-MB are conducted on A549 and HeLa tumor cells. FA-facilitated MSN-FA-TAN uptake is shown by HeLa cells that overexpress FA receptors via a FA-receptor-mediated endocytosis mechanism. The ultrasound response property of MSN-FA-TAN-MB is also verified. MSN-FA-TAN-MB shows significant antitumor efficacy in vivo with the assistance of FA, MB, and an external ultrasound irradiation. Thus, this multifunctional vehicle may provide a novel strategy for tumor targeting and imaging in tumor therapy.

Ultrasound responsive mesoporous silica nanoparticles for biomedical applications

“…A multidrug delivery vehicle was also developed with MSNs functionalised with folic acid and encapsulated into a microbubble. 78 Cytotoxicity and cellular uptake experiments we confirmed in vitro and the antitumor efficacy was corroborated in tumour bearing mice.…”

Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

“…Thus, ultrasound‐responsive nanomedicine may have advantages in the treatment of some kinds of deep‐seated cancer. Ultrasound technology has been widely used to microbubble or gas triggered drug delivery (Z. Chen et al, ; D. Gao et al, ; C. Huang, Zhang, & Bai, ; Lv et al, ; J. Wang et al, ; J. Zhang et al, ). In our group's previous work, the BNN6‐SPION@hMSN nanoparticle was prepared for a unique ultrasound‐triggered NO release (Z. Jin, Wen, Hu, et al, ).…”

“…Chen et al, 2018;C. Huang, Zhang, & Bai, 2017;Lv et al, 2017;. In our group's previous work, the BNN6-SPION@hMSN nanoparticle was prepared for a unique ultrasound-triggered NO release (Z.…”

Indocyanine green conjugated lipid microbubbles as an ultrasound-responsive drug delivery system for dual-imaging guided tumor-targeted therapy

“…The highest RV release rate was 89.7 AE 3.1% aer US irradiation for 60 s. These results showed that RILMBs-FA exhibited a suitable US-triggered drug release capability, likely due to the destruction of microbubbles leading to drug release. [34][35][36][37] 3.2 In vitro cellular uptake and biocompatibility Fig. 4a shows that intense ICG red uorescence could be observed in the perinuclear region in RILMBs-FA treated cells compared to that of free ICG and RILMBs treated cells.…”

“…Therefore, the results obtained throughout this study indicated the cell death mediated by apoptosis was induced by the release of RV, triggered by US irradiation. 35,40…”