A multifunctional nanocarrier based on nanogated mesoporous silica for enhanced tumor-specific uptake and intracellular delivery

A multifunctional drug delivery system based on MCM-41-type mesoporous silica nanoparticles is described that behaves as if nanogates were covalently attached to the outlets of the mesopores through a highly acid-sensitive benzoic-imine linker. Tumor-specific uptake and intracellular delivery results from the pH-dependent progressive hydrolysis of the benzoic-imine linkage that starts at tumor extracellular pH = 6.8 and increases with decreasing pH. The cleavage of the benzoic-imine bond leads to the removal of the polypseudorotaxane caps and subsequent release of the payload drugs at tumor sites. At the same time, the carrier surface becomes positively charged, which further facilitates cellular uptake of the nanocarriers, thus offering a tremendous potential for targeted tumor therapy.     

Hollow mesoporous silica nanoparticles modified with coumarin‐containing copolymer for photo‐modulated loading and releasing guest molecule

Hollow mesoporous silica nanoparticles (HMSNs) grafted with a photo‐responsive copolymer containing coumarin groups were successfully prepared. With uniform polystyrene nanoparticles and cetyltrimethylammonium bromide correspondingly as the template of core and channel, HMSNs were made from tetraethyloxysilane in alkalic condition. Epoxy groups were introduced onto the outer surface of HMSNs with γ‐(2,3‐epoxypropoxy)propyltrimethoxysilane and converted into azido groups with sodium azide, resulting in azido‐functionalized HMSNs (azido‐HMSNs). Meanwhile, single‐electron transfer‐living radical copolymerization of methyl methacrylate (MMA) and 7‐(2‐methacryloyloxy)‐4‐methylcoumarin (CMA) with propargyl 2‐bromoisobutyrate as the initiator produced alkynyl‐capped P(MMA‐co‐CMA) [alkynyl‐P(MMA‐co‐CMA)]. Finally, photo‐responsive HMSNs grafted with P(MMA‐co‐CMA) [HMSN‐g‐P(MMA‐co‐CMA)] was achieved through the click reaction between azido‐HMSNs and alkynyl‐P(MMA‐co‐CMA). Different techniques such as transmission electron microscopy, Fourier transform infrared spectroscopy, and thermal gravimetric analysis confirmed the successful preparation of the resultant hybrid nanoparticles and their intermediates. Because of its hollow core, mesoporous shell channels and light responsiveness, the coumarin‐modified HMSNs would be an interesting nano‐vehicle for guest molecules. Thus, the loading and release of pyrene with HMSN‐g‐P(MMA‐co‐CMA) was studied. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3791–3799     

Excellent correlation between drug release and portal size in metalla-cage drug-delivery systems

A series of large cationic hexanuclear metalla-prisms, [Ru(6)(p-iPrC(6)H(4)Me)(6)(tpt)(2)(donq)(3)](6+), [Ru(6)(p-iPrC(6)H(4)Me)(6)(tpt)(2)(doaq)(3)](6+) and [Ru(6)(p-iPrC(6)H(4)Me)(6)(tpt)(2)(dotq)(3)](6+), composed of p-cymene-ruthenium building blocks bridged by OO∩OO ligands (donq=5,8-dioxido-1,4-naphthoquinonato; doaq=5,8-dioxido-1,4-anthraquinonato, dotq=6,11-dioxido-5,12-naphthacenedionato) and connected by two 2,4,6-tripyridin-4-yl-1,3,5-triazine (tpt) panels, which encapsulate the guest molecules 1-(4,6-dichloro-1,3,5-triazin-2-yl)pyrene and Pd(acac)(2), have been prepared. The host-guest properties of these water-soluble delivery systems were studied in solution by NMR and fluorescence spectroscopy, providing the stability constants (K) for these host-guest systems. Moreover, the ability of the hosts to deliver the guests into cancer cells was evaluated and the uptake mechanism studied; the rate of release of the guest molecule was found to depend on the portal size of the host.     

Effective controlled release of captopril by silylation of mesoporous MCM-41.

The release of the water-soluble drug Captopril is controlled by tailoring the surface properties of mesoporous silica via stepwise silylation. The degree of silylation is manipulated by adjusting the initial concentration of silylanizing reagent (trimethylchlorosilane, TMCS). The silylanized and drug-loaded samples are characterized by powder X-ray diffraction, Fourier transform IR spectroscopy, N2 adsorption and desorption, 29Si cross-polarization magic angle spinning NMR spectroscopy, and transmission electron microscopy. The drug-loading amount is correlated to the Brunauer-Emmett-Teller surface area and surface hydrophilicity/hydrophobicity of the mesoporous silica material, while drug release profiles can be controlled by tailoring the surface properties and pore size.