Targeted anticancer prodrug with mesoporous silica nanoparticles as vehicles

Abstract

A targeted anticancer prodrug system was fabricated with 180 nm mesoporous silica nanoparticles (MSNs) as carriers. The anticancer drug doxorubicin (DOX) was conjugated to the particles through an acid-sensitive carboxylic hydrazone linker which is cleavable under acidic conditions. Moreover, folic acid (FA) was covalently conjugated to the particle surface as the targeting ligand for folate receptors (FRs) overexpressed in some cancer cells. The in vitro release profiles of DOX from the MSN-based prodrug systems showed a strong dependence on the environmental pH values. The fluorescent dye FITC was incorporated in the MSNs so as to trace the cellular uptake on a fluorescence microscope. Cellular uptakes by HeLa, A549 and L929 cell lines were tested for FA-conjugated MSNs and plain MSNs respectively, and a much more efficient uptake by FR-positive cancer cells (HeLa) can be achieved by conjugation of folic acid onto the particles because of the folate-receptor-mediated endocytosis. The cytotoxicities for the FA-conjugated MSN prodrug, the plain MSN prodrug and free DOX against three cell lines were determined, and the result indicates that the FA-conjugated MSN prodrug exhibits higher cytotoxicity to FR-positive cells, and reduced cytotoxicity to FR-negative cells. Thus, with 180 nm MSNs as the carriers for the prodrug system, good drug loading, selective targeting and sustained release of drug molecules within targeted cancer cells can be realized. This study may provide useful insights for designing and improving the applicability of MSNs in targeted anticancer prodrug systems.

Smart surface-enhanced Raman scattering traceable drug delivery systems

“…S1 †), the peak at 1720 cm −1 is attributed to the symmetric stretching of -CvO, which confirms the presence of carboxyl groups, while the 1657 cm −1 peak indicates the existence of -NH-CvO stretching vibrations. After removing Boc groups using TFA, 10 Au-SN-NHNH 2 was obtained. From the TEM image (Fig.…”

“…Unlike physical adsorption and diffusion, which may lead to premature, burst drug release and ultimately severe side effects, smart covalent linkages between the drug and carrier, especially carboxylic hydrazone links, [10][11][12] could bring effective impacts on sustainable drug release and reduce side effects, making the development of such smart DDSs a high priority.…”

Aptamer-Functionalized Silica Nanoparticles for Targeted Cancer Therapy

“…Normal L929 mouse fibroblast cells were used as the control cells [34][35][36] bioresource center, Japan, were cultured in monolayers to 80% confluence using 25 cm 2 tissue culture flasks. The cultures were maintained in Dulbecco's minimal essential medium, (Gibco) supplemented with 10% fetal bovine serum (Gibco), and 1% penicillin-streptomycin solution (Gibco) in a 5% CO 2 -humidified atmosphere at 37°C.…”

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

“…The control over the particle size and biocompatibility is of utmost importance in order to optimize the therapeutic efficacy and hence the applicability of nanoparticles 7,8 . Lipids [9][10][11][12][13] , polymers 14,15 , metals 16,17 and carbon nanotubes 18,19 have been commonly employed as nanocarriers for various biomedical and pharmaceutical applications.…”