Research Article
In vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: enhanced efficacy by folate modification

https://doi.org/10.1016/j.nano.2011.06.002Get rights and content

Abstract

Mesoporous silica nanoparticles (MSNs) have proven to be promising vehicles for drug delivery. However, despite the potential, few studies have extended the success of in vitro studies to animal settings. In this article, we report the efficacy of MSNs using two different human pancreatic cancer xenografts on different mouse species. Significant tumor-suppression effects were achieved with camptothecin-loaded MSNs. Dramatic improvement of the potency of tumor suppression was obtained by surface modifying MSNs with folic acid. Dose-dependent tumor suppression was observed, establishing 0.5 mg of CPT-loaded MSNs per mouse as a minimum dose sufficient for achieving complete tumor growth inhibition. Renal excretion of MSNs was also confirmed with transmission electron microscopy (TEM) imaging. These findings highlight attractive features (biocompatibility, renal clearance and high efficacy for delivering anticancer drugs) of MSNs as a drug-delivery system.

From the Clinical Editor

In this study, mesoporous silica nanoparticles are used as chemotherapy delivering agents in two different human pancreatic cancer xenografts and different mouse species. Significant tumor-suppression effects, biocompatibility and efficient renal clearance are demonstrated.

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.

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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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      Citation 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.

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