Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy

Abstract

Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems.

Characterization of a Mesoporous Silica Nanoparticle Formulation Loaded with Mitomycin C Lipidic Prodrug (MLP) and In Vitro Comparison with a Clinical-Stage Liposomal Formulation of MLP

“…Blank (drug-free) MSNPs were prepared through the same procedure as before to remove ethanol and tested in cell cultures of Panc-1 and T24 cells for 48–72 h. No inhibition of cell growth was found at nanoparticle concentrations in culture medium up to 0.1 mg/mL, indicating that the MSNPs were not toxic per se (data not shown). This is consistent with the general picture emerging from animal studies with MSNP, indicating that they are relatively nontoxic within an extended dose range, as recently reviewed [ 41 ]. Factors that may contribute to the lack of toxicity of MSNP in tissue culture are the low amount of pegylated MSNP taken up by non-phagocytic cells and the particle mesoporosity that should accelerate the bioerosion and breakdown processes to small secretable fragments and final dissolution to silicic acid.…”

Nanomedicine as an Emerging Technology to Foster Application of Essential Oils to Fight Cancer

“…MSNs occur in many forms (e.g., MCM-41, SBA-15, KCC-1, and KIT) and have been extensively used as drug delivery nanocarriers because of exceptional properties. They are characterized by stability (chemical and mechanical), easy synthesis and functionalization, a large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and a high drug-loading capacity, enabling multifunctional purposes and targeting [ 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 ].…”

Optimization of Nanoparticles for Smart Drug Delivery: A Review

“…In addition, the high aspect ratio enhanced surface functionalization, with better porosity to carry molecular cargo without any interference to the silica framework. MSNP's large Brunauer-Emmet-Teller (BET) surface area (700-1000 m 2 /g) and pore volume (0.6-1 cm 3 /g) also conduced to high drug loading (up to 50% w/w) so that it could adsorb multiple drug molecules [189]. Peng et al synthesized a core-shell hybrid nanoparticle composed of a copolymer shell with N-(3,4-dihydroxyphenethyl) methacrylamide (DMA) and N-isopropylacrylamide (NIPAM) as the response part.…”