Anand Kumar Meka

Biphasic Synthesis of Large‐Pore and Well‐Dispersed Benzene Bridged Mesoporous Organosilica Nanoparticles for Intracellular Protein Delivery

Large pore (4.6-7.6 nm) and well-dispersed benzene bridged mesoporous organosilica nanoparticles with uniform particle size of ≈50 nm are prepared via a biphasic approach. They can be directly used as nanocarriers without surface modification for the intracellular delivery of therapeutic proteins.

Nitrogen-doped ordered mesoporous carbon single crystals: Aqueous organic-organic self-assembly and superior supercapacitor performance

Nitrogen-doped ordered mesoporous carbon (NOMC) with a cubic Imm symmetry and rhombic dodecahedral single-crystal morphology has been successfully synthesized for the first time via organic–organic self-assembly of triblock copolymer, 3-aminophenol, and hexamethylenetetramine (HMTA) in basic aqueous solution. A steam treatment at elevated temperature has been developed to remove the surfactant from the as-synthesized sample, open the mesoporous cages, and create abundant micropores in the final product. Benefiting from the unique features of high surface area, uniform and uninterrupted mesopores, rich microporosity, and moderate nitrogen-doping (3.42%), the resultant NOMC single crystals show a high capacitance (281 F g−1 at 0.5 A g−1), excellent rate capability (195.5 F g−1 at 20 A g−1), and outstanding cycling stability (97% capacity retention after 5000 cycles at 5 A g−1) in electrochemical double-layer capacitors (EDLCs).

Mesoporous Magnesium Oxide Hollow Spheres as Superior Arsenite Adsorbent: Synthesis and Adsorption Behavior

Arsenic contamination in natural water has posed a significant threat to global health due to its toxicity and carcinogenity. Adsorption technology is an easy and flexible method for arsenic removal with high efficiency. In this Article, we demonstrated the synthesis of mesoporous MgO hollow spheres (MgO-HS) and their application as high performance arsenite (As(III)) adsorbent. MgO-HS with uniform particle size (∼180 nm), high specific surface area (175 m(2) g(-1)), and distinguished mesopores (9.5 nm in size) have been prepared by hard-templating approach using mesoporous hollow carbon spheres as templates. An ultrahigh maximum As(III) adsorption capacity (Qmax) of 892 mg g(-1) was achieved in batch As(III) removal study. Adsorption kinetic study demonstrated that MgO-HS could enable As(III) adsorption 6 times faster as a commercial MgO adsorbent. The ultrahigh adsorption capacity and faster adsorption kinetics were attributed to the unique structure and morphology of MgO-HS that enabled fast transformation into a flower-like porous structure composed of ultrathin Mg(OH)2 nanosheets. This in situ formed structure provided abundant and highly accessible hydroxyl groups, which enhanced the adsorption performance toward As(III). The outstanding As(III) removal capability of MgO-HS showed their great promise as highly efficient adsorbents for As(III) sequestration from contaminated water.

Understanding the contribution of surface roughness and hydrophobic modification of silica nanoparticles to enhanced therapeutic protein delivery

Intracellular protein delivery holds great promise for cancer therapy. In this work, the individual and combined contribution of the surface roughness and hydrophobic modification (octadecyl-group) of silica nanoparticles has been studied in a number of events for cellular delivery of therapeutic proteins, including loading capacity, release behaviour, cellular uptake and endo/lysosomal escape. Both surface roughening and hydrophobic modification enhance the protein adsorption capacity and sustained release, while the contribution from the surface roughness is higher for loading capacity and hydrophobic modification is more effective for sustained protein release. Both structural parameters improve the cellular uptake performance; however the difference in the contribution is cell type-dependent. Only the hydrophobic modification shows a contribution to endo/lysosomal escape, independent of the surface topography. Octadecyl-functionalized rough silica nanoparticles thus show the best performance in therapeutic protein (RNase A) delivery, causing significant cell viability inhibition in different cancer cells among all groups under study.

A vesicle supra-assembly approach to synthesize amine-functionalized hollow dendritic mesoporous silica nanospheres for protein delivery

Intracellular delivery of proteins is a promising strategy of intervention in disease, which relies heavily on the development of efficient delivery platforms due to the cell membrane impermeability of native proteins, particularly for negatively charged large proteins. This work reports a vesicle supra-assembly approach to synthesize novel amine-functionalized hollow dendritic mesoporous silica nanospheres (A-HDMSN). An amine silica source is introduced into a water-oil reaction solution prior to the addition of conventional silica source tetraethylorthosilicate. This strategy favors the formation of composite vesicles as the building blocks which further assemble into the final product. The obtained A-HDMSN have a cavity core of ≈170 nm, large dendritic mesopores of 20.7 nm in the shell and high pore volume of 2.67 cm3 g-1 . Compared to the calcined counterpart without amine groups (C-HDMSN), A-HDMSN possess enhanced loading capacity to large negative proteins (IgG and β-galactosidase) and improved cellular uptake performance, contributed by the cationic groups. A-HDMSN enhance the intracellular uptake of β-galactosidase by up to 5-fold and 40-fold compared to C-HDMSN and free β-galactosidase, respectively. The active form of β-galactosidase delivered by A-HDMSN retains its intracellular catalytic functions.

Floating tablets from mesoporous silica nanoparticles

Novel floating tablets are designed using mesoporous silica nanoparticles for enhancing the drug delivery performance of both hydrophobic and hydrophilic drugs compared to conventional floating tablets.

Hollow mesoporous carbon nanocarriers for vancomycin delivery: understanding the structure–release relationship for prolonged antibacterial performance

Mono-dispersed mesoporous hollow carbon (MHC) nanospheres with comparable structures have been designed as nanocarriers for the delivery of vancomycin (Van) to inhibit bacterial growth. It is demonstrated that MHC materials possess a Van loading capacity of 861 mg g-1, much higher than that of any Van nanocarrier in previous reports. By comparing the drug loading, release and antibacterial performance of MHC nanospheres with controllable structures, it is shown that MHC with a pore size of 5.8 nm and a wall thickness of 25 nm exhibits compromising storage-release behaviour and achieves extended bactericidal activity of Van towards E. coli and S. epidermidis compared to free Van and other MHC nanocarriers. This study provides new knowledge about the rational design of carbon based nanocarriers to enhance the therapeutic efficacy of antibiotics.

Asymmetric Silica Nanoparticles with Tunable Head–Tail Structures Enhance Hemocompatibility and Maturation of Immune Cells

Asymmetric mesoporous silica nanoparticles (MSNs) with controllable head-tail structures have been successfully synthesized. The head particle type is tunable (solid or porous), and the tail has dendritic large pores. The tail length and tail coverage on head particles are adjustable. Compared to spherical silica nanoparticles with a solid structure (Stöber spheres) or large-pore symmetrical MSNs with fully covered tails, asymmetrical head-tail MSNs (HTMSNs) show superior hemocompatibility due to reduced membrane deformation of red blood cells and decreased level of reactive oxygen species. Moreover, compared to Stöber spheres, asymmetrical HTMSNs exhibit a higher level of uptake and in vitro maturation of immune cells including dendritic cells and macrophage. This study has provided a new family of nanocarriers with potential applications in vaccine development and immunotherapy.

Pristine mesoporous carbon hollow spheres as safe adjuvants induce excellent Th2-biased immune response

The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capacity vaccine protein nanocarriers and safe adjuvants for boosting the immune response. Mono-dispersed invaginated mesostructured hollow carbon spheres (IMHCSs) have an average particle size of ∼200 nm, large pore size of 15 nm, and high pore volume of 2.85 cm3·g–1. IMHCSs exhibited a very high loading capacity (1,040 μg·mg–1) towards ovalbumin (OVA, a model antigen), controlled OVA release behavior, excellent safety profile to normal cells, and high antigen delivery efficacy towards macrophages. In vivo immunization studies in mice demonstrated that OVA-loaded IMHCSs induced a 3-fold higher IgG response compared to a traditional adjuvant QuilA used in veterinary vaccine research. OVA delivered by IMHCSs induced a higher IgG1 concentration than IgG2a, indicating a T-helper 2 (Th2)-polarized response. Interferon-γ and interleukin-4 concentration analysis revealed both T-helper 1 (Th1) and Th2 immune responses induced by OVA-loaded IMHCSs. IMHCSs are safer adjuvants than QuilA. Our study revealed that pure IMHCSs without further functionalization can be used as a safe adjuvant for promoting Th2-biased immune responses for vaccine delivery.

ε-Poly-L-Lysine/Plasmid DNA nanoplexes for efficient gene delivery in-vivo

&NA; The present work addresses the development and characterization of &egr;‐Poly‐L‐Lysine/pDNA polyplexes and evaluation for their improved transfection efficacy and safety as compared to polyplexes prepared using Poly‐L‐Lysine and SuperFect®. Self‐assembling polyplexes were prepared by varying the N/P ratio to obtain the optimum size, a net positive zeta potential and gel retardation. The stability in presence of DNase I and serum was assured using gel retardation assay. Their appreciable uptake in MCF‐7 and 3.5, 3.79 and 4.79‐fold higher transfection compared to PLL/pDNA polyplexes and 1.60, 1.53 and 1.79‐fold higher transfection compared to SuperFect®/pDNA polyplexes in MCF‐7, HeLa and HEK‐293 cell lines respectively, affirmed the enhanced transfection of &egr;‐PLL/pDNA polyplexes which was well supported with in vivo transfection and gene expression studies. The <8% in vitro hemolysis and >98% viability of MCF‐7, HeLa and HEK‐293 cells in presence of &egr;‐PLL/pDNA polyplexes addressed their safety, which was also ensured using in vivo toxicity studies, where hemocompatibility, unaltered levels of biochemical markers and histology of vital organs confirmed &egr;‐PLL to be an effective and safer alternative for non‐viral genetic vectors.