Immunostimulatory silica nanoparticle boosts innate immunity in brain tumors

Abstract

An immunostimulatory nanoparticle was specifically designed to boost the local innate immune compartment of brain tumors leading to a robust antitumor immune response.

The effect of PEGylation on the efficacy and uptake of an immunostimulatory nanoparticle in the tumor immune microenvironment

“…On the other hand, it has been shown that systemically administered silica nanoparticles deposit in the perivascular region of various murine tumor models, providing access to the numerous inactive innate immune cells present in this exact space. 19,22,23,37 Here, we observed that surface charge had a greater effect on the microdistribution and uptake of systemically administered MSNs by tumor-resident innate immune cells than the surface density of PEG itself.…”

“…3B). In a recent study, 19 we showed that mild acidication from pH 7.4 to pH 5.5 (mimicking late endosomal conditions) caused a 4-fold increase of CDN release from MSNs. Finally, the ability of immuno-MSN that immuno-MSN facilitated intracellular delivery and shuttled CDN out of endosomes and into the cytosol, which allowed direct access to STING.…”

“…Further, systemic administration of nanoparticles loaded with immunomodulatory drugs such as STING agonists offers many advantages, including convenient access to the entire tumor volume using the tumor microvasculature, preferential deposition within the tumor's perivascular niche that coincides with the APC-rich regions, and effective delivery to sites of early metastatic spread throughout the body. 12,[15][16][17][18][19][20][21] We designed an immunostimulatory nanoparticle loaded with a STING agonist (i.e., CDN) using mesoporous silica nanoparticles (termed immuno-MSNs). 19 The immuno-MSN provides an extremely high specic surface area, enabling a high drug-to-excipient ratio.…”

“…12,[15][16][17][18][19][20][21] We designed an immunostimulatory nanoparticle loaded with a STING agonist (i.e., CDN) using mesoporous silica nanoparticles (termed immuno-MSNs). 19 The immuno-MSN provides an extremely high specic surface area, enabling a high drug-to-excipient ratio. 22,23 Additionally, the mesoporous structure of MSNs can be readily functionalized with positively charged amines that can tightly bind the negative phosphonate groups of CDN.…”

The Promise and Challenges of Cyclic Dinucleotides as Molecular Adjuvants for Vaccine Development

“…In many cases, the treatment-induced substantial and durable systemic tumour-specific Th1 adaptive immunity is capable of rejecting distant metastases and providing long-lived immunologic memory [ 72 , 73 , 74 , 76 ]. The intratumoral CDN treatment also increased the response rate to T-cell receptor activation by checkpoint-modulating antibodies to CTLA-4, PD-1, 4-1BB, and OX40, resulting in significant increases in median survival time in animal models of melanoma (B16-F10 and YUMM1.7), breast adenocarcinoma (E0771), prostate cancer (TRAMP-C2), head and neck squamous cell cancers (SCCFVII) [ 72 , 73 ], HER-2 + breast tumours [ 76 ], glioblastoma multiforme [ 77 ], glioma [ 70 ], neuroblastoma [ 75 ], and 4T1 breast tumour [ 72 , 74 , 78 , 79 , 80 , 81 ]. In this regard, a single dose of cGAMP-liposomal nanoparticles (cGAMP-NP) was sufficient to modulate the tumour microenvironment for effective control of programmed death-ligand 1 (PD-L1)-insensitive basal-like triple-negative breast cancer and melanoma and, more significantly, prevented the formation of secondary tumours in mice [ 82 ].…”