Mesoporous Silica Nanoparticles for Dual-Mode Chemo-Sonodynamic Therapy by Low-Energy Ultrasound

Abstract

Low-energy ultrasound (LEUS), exhibiting obvious advantages as a safe therapeutic strategy, would be promising for cancer therapy. We had synthesized a LEUS-responsive targeted drug delivery system based on functional mesoporous silica nanoparticle for cancer therapy. Paclitaxel (PTX) was loaded in mesoporous silica nanoparticles with a hydrophobic internal channel, and folic acid (FA) functionalized β-Cyclodextrin (β-CD) was capped on the surface of the nanoparticles (DESN), which acted as a cancer-targeting moiety and solubilizer. The existence of a hydrophobic internal channel in the DESN was beneficial to the storage of hydrophobic PTX, along with the enhancement of the cavitation effect produced by mild low-energy ultrasound (LEUS, ≤1.0 W/cm2, 1 MHz). The DESN showed significantly enhanced cavitation effect, selective targeting, and achieved a rapid drug release under mild LEUS. To investigate the in vivo antitumor efficacy of the DESN upon LEUS irradiation, we established a 4T1 mammary tumor model. The DESN were confirmed to be of great biodegradability/biocompatibility. The tumor growth was significantly inhibited when the mice were treated with DESN (10 mg/kg) + LEUS with the relative tumor volume reduced to 4.72 ± 0.70 compared with the control group (V/V0 = 17.12 ± 2.75). The DESN with LEUS represented excellent inhibiting effect on tumor cell in vivo. This work demonstrated that DESN mediating dual mode chemo-sonodynamic therapy could be triggered by extracorporeal remote control, may suggest a promising clinical application in cancer therapy.

Mesoporous Silica Nanoparticles for Drug Delivery

“…[9], [113], [114], [115], [116], [117], [118], [119], [120] Ultrasounds is also an external stimulus that constitutes an efficient element for developing responsive MSNs with spatiotemporal control of the cargo delivery at the target site and preventing the damage of the healthy tissues. [121], [122], [123], [124], [125] Some of the benefits of Ultrasounds include its non-invasiveness, the absence of ionizing radiations and the easily regulation of tissue penetration depth by tuning some basic parameters.…”

Nanoparticle-Assisted Sonosensitizers and Their Biomedical Applications

“…be achieved through combining SDT and chemotherapy. 36,[69][70][71][72][73][74][75][76][77][78] Recently, Chen et al fabricated a self-assemble sonosensitizer composed of hydrophobic fluorescent dye chlorin e6 (Ce6), hydrophobic antitumor drug paclitaxel (PTX) and hydrophilic cyanine dye IR783 (named as Ce6-PTX @IR783, Figure 6). 69 Among these three parts, Ce6 can improve the efficacy of SDT, PTX was used for chemotherapy, and IR783 was applied for tumor-targeting and PAI.…”

Influence of the Surface Functionalization on the Fate and Performance of Mesoporous Silica Nanoparticles

“…Overall, the application of US leads to two main effects, namely acoustic cavitation (as noted in Section 2) and thermal effects, and it has been shown that both effects can lead to significantly higher drug release. In this regard, US can be effectively used to further enhance the effectiveness of functionalized nanoparticles, such as poly(dimethylsiloxane)-coated MSNs [376], polydopamine-coated MSNs [377] and β-CD-coated MSNs [378], achieving more amount of drugs released when used in combination with US.…”