Hollow Mesoporous Silica Nanoparticles with Extra-Large Mesopores for Enhanced Cancer Vaccine

Abstract

Owing to the limitations of conventional cancer therapies, cancer immunotherapy has emerged for the prevention of cancer recurrence. To provoke adaptive immune responses that are antigen-specific, it is important to develop an efficient antigen delivery system that can enhance the activation and maturation of the dendritic cells (DCs) in the human body. In this study, we synthesize hollow mesoporous silica nanoparticles with extra-large mesopores (H-XL-MSNs) based on a single-step synthesis from core–shell mesoporous silica nanoparticles with a core composed of an assembly of iron oxide nanoparticles. The hollow void inside the mesoporous silica nanoparticles with large mesopores allows a high loading efficiency of various model proteins of different sizes. The H-XL-MSNs are coated with a poly­(ethyleneimine) (PEI) solution to provide an immune adjuvant and change the surface charge of the particles for loading and slow release of a model antigen. An in vitro study using a cancer vaccine based on the PEI-coated H-XL-MSNs with the loading of the model antigen showed an enhanced activation of the DCs. An in vivo study demonstrated that the resulting cancer vaccine increased the antigen-specific cytotoxic T cells, enhanced the suppression of tumor growth, and improved the survival rate after challenging cancer to mice. These findings suggest that these hollow MSNs with extra-large pores can be used as excellent antigen carriers for immunotherapy.

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine

“…Given that MSNs can efficiently load high amounts of cargo, it is feasible to use MSNs for the delivery of cancer vaccines comprising protein antigens and immune adjuvants [ 414 , 415 ]. For example, Lee et al developed an antigen delivery system for enhancing the activation and maturation of dendritic cells using HMSNs with extra-large mesopores (H-XL-MSNs) and a core composed of iron oxide nanoparticles [ 85 ]. The surface of HMSNs was coated with poly(ethyleneimine) to change the surface charge of MSNs, allowing the efficient loading and release of antigens.…”

“…Furthermore, the in vivo studies in tumor-bearing mice showed a significant improvement in tumor suppression and recipient survival. These results suggest that HMSNs with extra-large pores are excellent carriers for cancer vaccines [ 85 ]. Besides, cyclic diguanylate monophosphate can activate the stimulator of interferon genes (STING) pathway, leading to the enhanced tumor immunogenicity, which in turn reverses the immunosuppressive tumor microenvironment.…”

Chemical Conjugation Strategies for the Development of Protein-Based Subunit Nanovaccines

“…Owing to their mesopores, high surface area, large pore volume, easy modification of physical and chemical functionalities, biocompatibility, and self-adjuvanticity, mesoporous silica nanoparticles (MSNs) are considered to be one of the most promising inorganic nanocarriers [157]. Thalhauser et al proved that covalent conjugates of MSNs and antigens were able to elicit stronger immune responses compared to their noncovalent counterparts in a study where they conjugated HIV-1 envelope trimers onto the surface of MSNs via maleimide-thiol chemistry [158].…”

Silicon nanoparticles (SiNPs) in sustainable agriculture: major emphasis on the practicality, efficacy and concerns

“…In contrast to this, the MSN has a pore size of around 2 to 20 nm and is widely used for drug delivery [55][56] . Hollow mesoporous (HMSN) SiNPs are spherical-shaped and have a large hole in the center, and they can be used for loading of antigen to activate the immune system 57 . Core-shell SiNP is the spherical silica particle having solid cores and mesoporous shell 58 .…”