Prasanna Lakshmi Abbaraju

Multi-shelled dendritic mesoporous organosilica hollow spheres: roles of composition and architecture in cancer immunotherapy

Developing potent adjuvants for the stimulation of robust immune response is central for effective cancer immunotherapy. Double-shelled dendritic mesoporous organosilica hollow spheres are an excellent adjuvant and provide superior immunity in cancer immunotherapy, and better than their counterparts either with a pure silica composition or a single-walled architecture. This study provides new insights in the rational design of effective nanostructured adjuvants for vaccine developments.

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.

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.

Core-shell-structured dendritic mesoporous silica nanoparticles for combined photodynamic therapy and antibody delivery

Multifunctional core-shell-structured dendritic mesoporous silica nanoparticles with a fullerene-doped silica core, a dendritic silica shell and large pores have been prepared. The combination of photodynamic therapy and antibody therapeutics significantly inhibits the cancer cell growth by effectively reducing the level of anti-apoptotic proteins.

Understanding the Effect of Surface Chemistry of Mesoporous Silica Nanorods on Their Vaccine Adjuvant Potency

Mesoporous silica nanoparticles are reported as adjuvants in nanovaccines in generating robust antigen-specific immunity. However, the effect of surface chemistry in initiating and modulating the immune response remains largely unexplored. In this study, mesoporous silica nanorods (MSNRs) are modified with NH2 and C18 groups to investigate the influence of surface functional groups (OH, NH2 , and C18 ) on their adjuvant efficacy. It is found that compared to OH and NH2 groups, the hydrophobic C18 modification significantly enhances antigen uptake by antigen presenting cells and endosomal-lysosomal escape in vitro, dendritic cells, and macrophages maturation ex vivo, and elicits secretion of interferon-γ level and antibody response in immunized mice. Moreover, bare MSNR and MSNRNH2 exhibit T-helper 2 biased immune response, while MSNRC18 shows a T-helper 1 biased immune response. These findings suggest that the surface chemistry of nanostructured adjuvants has profound impact on the immune response, which provides useful guidance for the design of effective nanomaterial based vaccines.

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.

Asymmetric mesoporous silica nanoparticles as potent and safe immunoadjuvants provoke high immune responses

Asymmetric mesoporous silica nanoparticles with a head-tail structure are potent immunoadjuvants for delivering a peptide antigen, generating a higher antibody immune response in mice compared to their symmetric counterparts.