Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy

Abstract

Conventional adjuvants (e.g., aluminum) are insufficient to trigger cell-mediated immunity, which plays a crucial role in triggering specific immunity against cancer. Therefore, developing appropriate adjuvants for cancer vaccines is a central way to stimulate the antitumor immune response. Hollow mesoporous silica nanoparticles (HMSNs) have been proven to stimulate Th1 antitumor immunity in vivo and promote immunological memory in the formulation of novel cancer vaccines. Yet, immune response rates of existing HMSNs for anticancer immunity still remain low. Here, we demonstrate the generation of polyethylenimine (PEI)-incorporated thin-shell HMSNs (THMSNs) through a facile PEI etching strategy for cancer immunotherapy. Interestingly, incorporation of PEI and thin-shell hollow structures of THMSNs not only improved the antigen-loading efficacy and sustained drug release profiles but also enhanced the phagocytosis efficiency by dendritic cells (DCs), enabled DC maturation and Th1 immunity, and sustained immunological memory, resulting in the enhancement of the adjuvant effect of THMSNs. Moreover, THMSNs vaccines without significant side effects can significantly reduce the potentiality of tumor growth and metastasis in tumor challenge and rechallenge models, respectively. THMSNs are considered to be promising vehicles and excellent adjuvants for the formulation of cancer vaccines for immunotherapy.

Inorganic Nanoparticles Applied as Functional Therapeutics

“…[ 176 ] Our recent report demonstrated that the hybrid of hollow MSN with positive polymer can remarkably promote their degradable rate. [ 177 ] Furthermore, enhancing the accumulation of inorganic therapeutics in targeted disease‐affected tissues remains a significant challenge and is yet to be solved. For certain diseases, local injection may be considered an alternative drug delivery method for systemic administration.…”

Fabrication data of two light-responsive systems to release an antileishmanial drug activated by infrared photothermal heating

“…In acid medium, the amino groups can be protonated and the polymer becomes cationic [8] . Because of the positive surface charge of different materials functionalized with PEI, cell uptake efficiency can be improved [9] . This polymer has been widely applied in regenerative medicine and gene therapy as deliver expression systems [10] .…”

Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

“…In addition, MSNs possess adjuvant behaviors due to the properties of morphology, size, and modified groups 140 . Thus far, a myriad of functionalized silica nanoparticles, acting as adjuvants or carriers, have been used for therapeutic cancer vaccines 141,142 . For example, various types of hollow MSNs have been considered as promising vaccine adjuvants to direct humoral and cellular immune responses and subsequently deprive tumor cells during tumor challenge 143 .…”