Multifunctional hybrid silica nanoparticles for controlled doxorubicin loading and release with thermal and pH dual response

Abstract

Controlled drug loading and release into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to resistance and inefficient cellular uptake. Here a temperature and pH dually responsive PNiPAM/AA@SiO2 core-shell particles with internal controlled release were designed and fabricated for efficient cancer treatment, which could recognize the intrinsic pH differences between cancers and normal tissues. Upon lowering the temperature, doxorubicin was loaded into the PNiPAM/AA@SiO2 nanoparticles, whereas by increasing the acidity, previously loaded doxorubicin was quickly released. Comparing with common mesoporous silica particles (MSNs), this core-shell particle has more uniform size and better dispersity. In addition, dried PNiPAM/AA@SiO2 nanoparticles could be easily redispersed in distilled water. The in vitro cell culture experiments showed that not only PNiPAM/AA@SiO2 particles were more biocompatible and lower cytotoxic than MSN, but also DOX@PNiPAM/AA@SiO2 had higher drug releasing efficiency in the lysosomes and stronger inhibitory effect on tumor cell growth than DOX@MSN. All these features indicated that PNiPAM/AA@SiO2 particles have great potential in therapy applications.

Adsorption of antitumor antibiotic doxorubicin on MCM-41-type silica surface

“…Among them, ordered mesoporous silicas of MCM-41 type are the most promising solid supports for the formation of biologically active systems (Aznar et al, 2011;Bernardos et al, 2010;Gu et al, 2012;Hu et al, 2013;Knezevic et al, 2011Knezevic et al, , 2013Lee et al, 2010Lee et al, , 2011Meng et al, 2010;Prokopowicz et al, 2016;Yuan et al, 2011). Besides chemical stability and biocompatibility, the potential importance of MCM-41 silica materials as drug carriers is caused by their high surface area, large pore volume, uniform and tunable pores of molecular size, and controllable participation in chemical reactions with a wide range of modifiers.…”

“…In order to prevent undesirable release of Dox molecules at the first contact of carrier with aqueous solution and provide their liberation only in specific time and location, stimuli-responsive structures were constructed on MCM-41 surface. In particular, effective Dox release systems, which respond to the enzyme presence (Bernardos et al, 2010), light initiation (Knezevic et al, 2011), pH change (Bernardos et al, 2010;Gu et al, 2012;Hu et al, 2013;Knezevic et al, 2011;Lee et al, 2010Lee et al, , 2011Meng et al, 2010;Yuan et al, 2011), and temperature variation (Aznar et al, 2011;Hu et al, 2013), were reported. At the same time, because of the low loading efficiency of initial MCM-41 (up to 2.6 wt.%) (Kim et al, 2013), many attempts were made to enhance affinity between Dox molecules and silica surface by lining mesopore walls with functional groups (Kardys et al, 2013;Kim et al, 2013;Knezevic et al, 2011;Ma et al, 2014) or immobilization of polymer moieties on outer surface of silica particles (Kim et al, 2013).…”

“…In order to minimize undesired damages of healthy cells without reducing therapeutic action of Dox, drug carrier systems are widely used (Aznar et al, 2011;Bernardos et al, 2010;Chen et al, 2013;Gao et al, 2011;Gu et al, 2012;Hu et al, 2013;Knezevic et al, 2011Knezevic et al, , 2013Lee et al, 2010Lee et al, , 2011Maeda et al, 2003;Meng et al, 2010;Mishra et al, 2014;Nishiyama and Kataoka, 2003;Prokopowicz and Przyjazny, 2007;Prokopowicz et al, 2016;Safari and Zarnegar, 2014;Singh et al, 2011;Tan et al, 2011;Wang et al, 2011;Yang et al, 2008;Yokoyama, 2011;Yuan et al, 2011;Zhang et al, 2011). Among them, ordered mesoporous silicas of MCM-41 type are the most promising solid supports for the formation of biologically active systems (Aznar et al, 2011;Bernardos et al, 2010;Gu et al, 2012;Hu et al, 2013;Knezevic et al, 2011Knezevic et al, , 2013Lee et al, 2010Lee et al, , 2011Meng et al, 2010;Prokopowicz et al, 2016;Yuan et al, 2011).…”

The Effect of Chlorpyrifos, an Organophosphorus Pesticide, on Glucose Uptake in Whole Blood

“…Hemolysis assay was done by method as described by Hu et al [13]. Two ml of heparinized blood was added to 4 ml sterile Dulbecco's phosphate buffer saline (DPBS) and centrifuged at 3000 rpm for 5 min using clinical centrifuge (REMI R-8C) to wash Red Blood Cells (RBCs).…”

Development and Evaluation of High Oxaliplatin Loaded CS-g-PNIPAAm Co-Polymeric Nanoparticles for Thermo and pH Responsive Delivery

“…14,15 Taking these differences as a basic concept, various pH and temperature responsive polymers were synthesized and utilized as carriers for stimuli-responsive delivery of anti-cancer drugs. [16][17][18][19][20] Though all these reported polymeric nanoparticles have shown tremendous potential for targeted drug delivery, they have a very low drug loading capacity. Among them, due to the closer LCST (32 o C) of PNIPAAm to normal body temperature, biocompatibility and non-toxicity, chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) co-polymer was most extensively studied as a carrier for anticancer drugs to achieve thermo and pH responsive delivery of drugs to the intended sites with minimal or no adverse effects in cancer therapy.…”