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After the introduction of first generation MSNs for drug delivery with some challenges such as large particle sizes, irregular morphologies and aggregations, second generation provided uniform spherical morphologies, tunable pore/particle sizes and compositions. Henceforth, organic‐inorganic hybrid mesoporous silica nanosystems have grown rapidly and utilized for active and passive targeting of tumorigenic cells especially conjugated with organic polymers followed by third generation counterparts with improved functionalities for cancer therapy. The aim of this review article is to focus on the advancements in mesoporous silica based organic‐inorganic hybrid nanoparticles developed as drug carriers targeting cancer cells. Brief introduction to the state‐of‐the‐art in passive and active targeting methods is presented. Specifically, therapeutic, diagnostic and theranostic applications are discussed with emphases on triggered and ligand conjugated organic‐inorganic hybrid mesoporous silica nanomaterials. Although mesoporous silica nanoparticles perform well in preclinical tests, clinical translation progresses slowly as appropriate doses needs to be evaluated for human use along with biocompatibility and efficiency depending on surface modifications.

BACKGROUNDPropolis exhibits therapeutic properties due to the presence of phenolic acids, esters, and flavonoids. The scope of this study was to develop a nano‐vesicular formulation and establish a three‐dimensional (3D) spheroid model in which lung cancer is recapitulated.RESULTSNiosome vesicles doped with galangin‐rich propolis extract were synthesized by the ether injection method using a cholesterol : surfactant mass ratio of 1 : 3 at 40 °C for 1 h. Formulated niosomes were administered to 3D lung cancer spheroid model and the cytotoxicity was compared with that of a two‐dimensional (2D) setting. The galangin content was determined as 86 μg mg–1 propolis extract by ultra‐performance liquid chromatography (UPLC). The particle size of loaded niosome was 151 ± 2.84 nm with a polydispersity index (PDI) of about 0.232, and an encapsulation efficiency of 70% was achieved.CONCLUSIONThe decrease in cell viability and the scattering in the 3D spheroids of A549 lung cancer cells treated with propolis‐loaded niosomes were notable, indicating a profound cytotoxic effect and suggesting that they can be utilized as an effective nano‐vesicle. © 2020 Society of Chemical Industry

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Lamellar and non-lamellar liquid crystalline nanodispersions, including liposomes, cubosomes, and hexosomes are attractive platforms for drug delivery, bio-imaging, and related pharmaceutical applications. As compared to liposomes, there is a modest number of reports on the continuous production of cubosomes and hexosomes. Using a binary lipid mixture of citrem and soy phosphatidylcholine (SPC), we describe the continuous production of nanocarriers for delivering thymoquinone (TQ, a substance with various therapeutic potentials) by employing a commercial microfluidic hydrodynamic flow-focusing chip. In this study, nanoparticle tracking analysis (NTA) and synchrotron small-angle X-ray scattering (SAXS) were employed to characterize TQ-free and TQ-loaded citrem/SPC nanodispersions. Microfluidic synthesis led to formation of TQ-free and TQ-loaded nanoparticles with mean sizes around 115 and 124 nm, and NTA findings indicated comparable nanoparticle size distributions in these nanodispersions. Despite the attractiveness of the microfluidic chip for continuous production of citrem/SPC nano-self-assemblies, it was not efficient as comparable mean nanoparticle sizes were obtained on employing a batch (discontinuous) method based on low-energy emulsification method. SAXS results indicated the formation of a biphasic feature of swollen lamellar (Lα) phase in coexistence with an inverse bicontinuous cubic Pn3m phase in all continuously produced TQ-free and TQ-loaded nanodispersions. Further, a set of SAXS experiments were conducted on samples prepared using the batch method for gaining further insight into the effects of ethanol and TQ concentration on the structural features of citrem/SPC nano-self-assemblies. We discuss these effects and comment on the need to introduce efficient microfluidic platforms for producing nanocarriers for delivering TQ and other therapeutic agents.

In this study, the neoplastic drug frequently used in the treatment of lung cancer, carboplatin is loaded to microbubbles via a microfluidic platform. In order to increase the drug loading capacity of microbubbles, carboplatin is encapsulated into alginate polymer layer. The phospholipid microbubbles (MBs) are synthesized by MicroSphere Creator, which is connected with T‐junction and micromixer for the treatment with CaCl2 solution to provide gelation of the alginate coated phospholipid microbubbles (AMBs). The carboplatin loaded alginate coated phospholipid microbubbles (CAMBs) result in 12.2 ± 0.21 µm mean size, obtained by mixing with 0.05% CaCl2 using T‐junction. The cytotoxic activities of the synthesized MBs, AMBs, and CAMBs are also investigated with the 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) (MTT) and live/dead fluorescent dying assays in the A549 and BEAS‐2B cell lines. The one‐step microfluidic coating of lipid microbubbles with natural alginate polymer appears to be a promising strategy for enhanced drug reservoir properties.

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