Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells

Abstract

Using nanoparticles to deliver chemotherapeutics offers new opportunities for cancer therapy, but challenges still remain when they are used for the delivery of multiple drugs, especially for the synchronous delivery of hydrophilic and hydrophobic drugs in combination therapies. In this paper, we developed an approach to deliver hydrophilic-hydrophobic anticancer drug pairs by employing magnetic mesoporous silica nanoparticles (MMSNs). We prepared 50 nm-sized MMSNs with uniform pore size and evaluated their capability for the loading of two combinations of chemotherapeutics, namely doxorubicin-paclitaxel and doxorubicinrapamycin, by means of sequential adsorption from the aqueous solution of doxorubicin and nonaqueous solutions of paclitaxel or rapamycin. Experimental results showed that the present strategy successfully realized the co-loading of hydrophilic and hydrophobic drugs with high-loading content and widely tunable ratio range. We elaborate on the theory behind the molecular interaction between the silica hydroxyl groups and drug molecules, which underlie the controllable loading, and the subsequent release of the drug pairs. Then we demonstrate that the multidrug-loaded MMSNs could be easily internalized by A549 human pulmonary adenocarcinoma cells, and produce enhanced tumor cell apoptosis and growth inhibition as compared to single-drug loaded MMSNs. Our study thus realized simultaneous and dose-tunable delivery of hydrophilic and hydrophobic drugs, which were endowed with improved anticancer efficacy. This strategy could be readily extended to other chemotherapeutic combinations and might have clinically translatable significance.

Controlled drug release from pharmaceutical nanocarriers

“…The three drugs were released from the PLGA NPs showing distinct patterns according to their aqueous solubility (PNS > Sal B > TS IIA) (Zhang et al, 2013). In another example, DOX and PTX or another hydrophobic immunosuppressant rapamycin (RAPA) were loaded in mesoporous silica NPs with an iron oxide core (Qian Liu, 2012). Co-encapsulation of two drugs with different water solubility was achieved by a sequential adsorption procedure, namely, loading DOX in aqueous solution first, followed by adsorbing RAPA (or PTX) in non-aqueous medium, where the former was attracted to the silica matrix via electrostatic interactions and the latter through hydrogen bonding and polar interactions with silica (Qian Liu, 2012).…”

“…In another example, DOX and PTX or another hydrophobic immunosuppressant rapamycin (RAPA) were loaded in mesoporous silica NPs with an iron oxide core (Qian Liu, 2012). Co-encapsulation of two drugs with different water solubility was achieved by a sequential adsorption procedure, namely, loading DOX in aqueous solution first, followed by adsorbing RAPA (or PTX) in non-aqueous medium, where the former was attracted to the silica matrix via electrostatic interactions and the latter through hydrogen bonding and polar interactions with silica (Qian Liu, 2012). The drug release followed the Korsmeyer-Peppas model with a release exponent n value of 0.45, indicative of simple diffusion-controlled Fickian process.…”

“…The drug release followed the Korsmeyer-Peppas model with a release exponent n value of 0.45, indicative of simple diffusion-controlled Fickian process. The presence of hydrophobic RAPA or PTX restricted the kinetics of water diffusion, the first step of diffusion-controlled release process, resulting in slower DOX release than from the system with DOX alone (Qian Liu, 2012). …”

Materials innovation for co-delivery of diverse therapeutic cargos

“…Recently, a group developed a simple sequential loading method using different solvents to load a hydrophobic and hydrophilic drug (DOX-paclitaxel and DOX-rapamycin) within the pores of an MSNP through molecular interaction between the hydroxyl groups of silica and the drug molecules. In addition to obtaining a high loading of the hydrophobic and hydrophilic drug, they were also able to manipulate the ratio of the two drugs loaded by varying the feed ratio 116 . The next generation of MSNP carriers is likely to be a multifunctional system endowed with targeting, stimuli-responsive, multiple-release, and theranostic capabilities.…”

Synthesis and surface modification of magnetic nanoparticles for potential applications in sarcomas

“…In addition to particle size, biocompatibility, bioavailability, multi-functionality, and multimodality of IONPs are substantially enhanced by surface coatings, such as polyethylene glycol (PEG; Boyer et al 2010;Li et al 2005), D-glucose (DG; Harris and Chess 2003), and mesoporous silica (Huang et al 2011a, b;Liu et al 2012;Li et al 2014;Lien et al 2011). Coating enhances the colloidal stability decreasing aggregation and preventing oxidation, which increases endocytic efficiency by target cells (Petri Fink et al 2005).…”