Research ArticleIn vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: enhanced efficacy by folate modification
Graphical Abstract
Significant tumor-suppression effects were achieved with camptothecin-loaded mesoporous silica nanoparticles (MSNs). Dramatic improvement of the potency of tumor suppression was obtained by surface modifying MSNs with folic acid. These findings highlight attractive features (biocompatibility, renal clearance and tumor-suppressing ability) of MSNs as a drug-delivery system.
Section snippets
Synthesis of mesoporous silica nanoparticles
MSNs were synthesized by first dissolving fluorescein isothiocyanate (FITC; 5.5 mg) in absolute ethanol (3 mL) before adding aminopropyltriethoxysilane (APTS; 12 μL). In another container, cetyltrimethylammonium bromide (CTAB; 0.5 g) was dissolved in a solution of distilled water (240 mL) and sodium hydroxide (2 M, 1.75 mL) that was heated to 80°C and stirred vigorously. The FITC/APTS solution was stirred under an inert atmosphere for 2 hours before adding tetraethylorthosilicate (TEOS; 2.5
Synthesis and characterization of MSNs
MSNs provide an attractive vehicle for delivering anticancer drugs. The NPs were synthesized by the sol-gel method using surfactants as described previously.1 To increase dispersibility of the NPs, phosphonates are included to surface modify the particles. Scanning electron microscopy (SEM) and TEM analyses showed that the MSNs we used are roughly spherical in shape and approximately 100 – 130 nm in diameter, with hexagonal arrays of the pores (Figure 1, A). An average pore diameter of
Discussion
In this study we have shown that CPT-loaded MSNs are effective in suppressing tumor growth of 2 different human pancreatic cancer xenografts, PANC-1 and MiaPaCa-2. In addition, we used 2 different animal species, nude mice and SCID mice. The growth of PANC-1 tumors in the nude mice treated with CPT-loaded MSNs was significantly suppressed, with very small tumors or almost complete elimination observed at the end of the treatment. With MiaPaCa-2 xenografts in nude mice, we observed regression of
Supplementary data
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References (27)
- et al.
EPR effect based drug design and clinical outlook for enhanced cancer chemotherapy
Adv Drug Deliv Rev
(2011) - et al.
Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers
Adv Drug Deliv Rev
(2008) - et al.
Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs
Small
(2007) - et al.
Mesoporous silica nanoparticles for cancer therapy: energy-dependent cellular uptake and delivery of paclitaxel to cancer cells
Nanobiotechnology
(2007) - et al.
Targeted intracellular delivery of hydrophobic agents using mesoporous hybrid silica nanoparticles as carrier systems
Nano Lett
(2009) - et al.
Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery
ACS Nano
(2008) - et al.
Uptake of functionalized mesoporous silica nanoparticles by human cancer cells
J Nanosci Nanotechnol
(2010) - et al.
Cancer-cell-specific induction of apoptosis using mesoporous silica nanoparticles as drug-delivery vectors
Small
(2010) - et al.
Biofunctionalized phospholipid-capped mesoporous silica nanoshuttles for targeted drug delivery: improved water suspensibility and decreased nonspecific protein binding
ACS Nano
(2010) - et al.
Mechanised nanoparticles for drug delivery
Nanoscale
(2009)
Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals
Small
Mesoporous silica nanoparticles facilitate delivery of siRNA to shutdown signaling pathways in mammalian cells
Small
Mesoporous silica nanoparticle-based double drug delivery system for glucose-responsive controlled release of insulin and cyclic AMP
J Am Chem Soc
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2022, Journal of Colloid and Interface ScienceCitation Excerpt :An ever increasing number of studies demonstrate that mesoporous silica nanoparticles (MSNs) are promising drug carriers for intracellular drug delivery in vitro and in vivo [1–6]. Although the in vivo studies are to date limited to small animal studies, several studies demonstrate an enhanced therapeutic outcome when the drug is administered incorporated into MSNs as compared to when the drug is administered in free form [7–9]. Reasons that can enhance the therapeutic outcome when formulating drugs using nanoparticles like MSN include enhanced drug stability against enzymatic degradation, enhanced target organ/cell type specificity, and enhanced blood circulation time of the drug [10–15].
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This work was supported by the NIH grant CA133697.
The authors report no conflict of interest.