<p>Targeted anticancer potential against glioma cells of thymoquinone delivered by mesoporous silica core-shell nanoformulations with pH-dependent release</p>

Abstract

Background and purpose Glioma is one of the most aggressive primary brain tumors and is incurable. Surgical resection, radiation, and chemotherapies have been the standard treatments for brain tumors, however, they damage healthy tissue. Therefore, there is a need for safe anticancer drug delivery systems. This is particularly true for natural prodrugs such as thymoquinone (TQ), which has a high therapeutic potential for cancers but has poor water solubility and insufficient targeting capacity. We have tailored novel core-shell nanoformulations for TQ delivery against glioma cells using mesoporous silica nanoparticles (MSNs) as a carrier. Methods The core-shell nanoformulations were prepared with a core of MSNs loaded with TQ (MSNTQ), and the shell consisted of whey protein and gum Arabic (MSNTQ-WA), or chitosan and stearic acid (MSNTQ-CS). Nanoformulations were characterized, studied for release kinetics and evaluated for anticancer activity on brain cancer cells (SW1088 and A172) and cortical neuronal cells-2 (HCN2) as normal cells. Furthermore, they were evaluated for caspase-3, cytochrome c, cell cycle arrest, and apoptosis to understand the possible anticancer mechanism. Results TQ release was pH-dependent and different for core and core-shell nanoformulations. A high TQ release from MSNTQ was detected at neutral pH 7.4, while a high TQ release from MSNTQ-WA and MSNTQ-CS was obtained at acidic pH 5.5 and 6.8, respectively; thus, TQ release in acidic tumor environment was enhanced. The release kinetics fitted with the Korsmeyer–Peppas kinetic model corresponding to diffusion-controlled release. Comparative in vitro tests with cancer and normal cells indicated a high anticancer efficiency for MSNTQ-WA compared to free TQ, and low cytotoxicity in the case of normal cells. The core-shell nanoformulations significantly improved caspase-3 activation, cytochrome c triggers, cell cycle arrest at G2/M, and apoptosis induction compared to TQ. Conclusion Use of MSNs loaded with TQ permit improved cancer targeting and opens the door to translating TQ into clinical application. Particularly good results were obtained for MSNTQ-WA.

Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles

“…The specific surface area, total pore volume, and pore size were greatly decreased when particles were loaded with Pip, coated with GA, and conjugated to FA compared to the starting material for both HAPs and HAP-Ps. This observation is expected and in agreement with previous studies [30,31,36]. Interestingly, the pore size distributions calculated by BET method from N2 adsorption/desorption measurements showed that HAPs had a pore size ranging from 9 nm to 13 nm.…”

“…This observation can be explained by most Pip molecules being entrapped inside pores on the surface of HAPs. These results are in agreement with reports of loading drugs in mesoporous nanoparticles [30,31,63]. Changing the crystalline state of a water-insoluble drug to the non-crystalline state using mesoporous materials can enhance solubility, increasing the drug therapeutic activity [64].…”

“…The EE reached 72-81wt % depending on the presence or absence of the GA coating and FA conjugation. The drug content calculated based on TG analysis was reported previously for inorganic nanoparticles used in drug delivery [31,62]. The second way was UV-vis spectroscopy, which is a commonly used method in most drug delivery strategies.…”

“…Cytotoxicity and anticancer activity against MCF7, Caco2, and WI-38 cells were assessed as described previously [31]. We tested HAPs and HAP-Ps for cytotoxicity at 12.3, 37, 111, 333, and 1000 µg/mL.…”

“…This effect is expected since release depends on degradation of the polymeric drug carrier such as chitosan, which takes place in short time. Inorganic nanocarriers used in drug delivery systems (DDSs) for drugs and therapeutic agents have included mesoporous silica nanoparticles (MSNs), magnetic nanoparticles, zinc nanoparticles, and others to treat various diseases [30][31][32][33]. Hydroxyapatite is the primary inorganic component of teeth and bone.…”