Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

Abstract

Introduction Metastatic breast cancer seriously harms women’s health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects. Methods The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds. Results The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis. Conclusion The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer.

Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

“…Aptamers show similar targeting ability but they are non-immunogenic and easier to produce. In this sense, Zhuang et al employed the aptamer AS1411, which targets the nucleolin protein, to engineer a redox-responsive gatekeeper for the MSNs [ 44 ]. Rather than merely loading doxorubicin, they incorporated a thiolated siRNA able to inhibit TIE2 to sensitize doxorubicin-resistant breast tumors.…”

pH-Responsive Drug Delivery and Imaging Study of Hybrid Mesoporous Silica Nanoparticles

“…To achieve the release of the drug in the targeted diseased tissues, several surface-functionalized coatings as gatekeepers are modified onto the MSN carriers to block the drug in the pore channels [ 19 , 20 , 21 , 22 ]. Various types of stimuli could be used to open the gatekeepers, such as pH [ 23 , 24 ], enzymes [ 25 ], redox [ 26 , 27 ], light [ 28 ], ultrasound [ 29 ], and temperature [ 30 ].…”

Synthesized and release study of labelled small mesoporous silica nanoparticle as theranostic material

“…It has several unique characteristics that support as carrier such as high surface area, tunable morphology, biocompatible, and non-toxic [14][15][16][17]. Some drugs have been successfully loaded into MSN such as doxorubicin, methotrexate, mitoxantrone, quercetin, curcumin, and metallodrug [18][19][20][21][22][23][24][25][26][27]. The drug loading process is influenced by MSN morphology, such as particle size and surface area [28,29].…”