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

Jingjing Wang,Yiran Shao,Yajing Jiao

doi:10.3390/ma11102041

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.

Highlights

Cancer is one of the most serious diseases threatening the health of human beings.Cooperative therapeutic strategies, which may overcome the intrinsic shortages of traditional chemotherapy, have drawn great attention in recent years [1,2,3]
Dual-Effect Mesoporous Silica Nanoparticles (DESN) with accurate weight were immersed in four same PBS solutions and treated under low-energy ultrasound irradiation with different intensities (1 MHz; 0.4, 0.6, 0.8, and 1.0 W·cm−2 )
mesoporous silica nanoparticles (MSN) and DESN were dispersed in the terephthalic acid (TA)-PBS solution (20 mL, 1 μg·mL−1 ), respectively

Summary

Introduction

Cooperative therapeutic strategies, which may overcome the intrinsic shortages of traditional chemotherapy, have drawn great attention in recent years [1,2,3]. Chemotherapy assisted by ultrasound based on mesoporous silica nanomaterials has been intensively investigated for improving cancer treatment [4,5]. Ultrasound recently aroused increasing interest as a preferable tool for cancer diagnostics because of its noninvasiveness, nonionizing nature, cost-effectiveness and easy regulation of tissue penetration depth by tuning the frequency, cycles, and exposure time [6,7]. Ultrasound was one of the most promising external triggers for achieving spatiotemporal control of the drug release at the desired site, and has been shown to enhance nanoparticles’ extravasation through blood capillaries, increase cell membrane permeation, and even induce an immune response against tumors [6,8,9].

Results

Discussion

Conclusion