BN nanospheres functionalized with mesoporous silica for enhancing CpG oligodeoxynucleotide-mediated cancer immunotherapy

Abstract

CpG oligodeoxynucleotides (CpG ODNs) possess strong immunostimulatory activity, which hold great promise in cancer immunotherapy. However, their therapeutic efficacy is largely limited due to nuclease degradation and poor cellular internalization. Efficiently delivering CpG ODNs into target cells is crucial to improve their therapeutic efficacy. Boron nitride nanospheres (BNNS) possess advantage as carriers for CpG ODNs. However, their poor aqueous dispersity and low CpG ODN loading capacity became a big obstacle for further applications. Herein, we develop amino group grafted, mesoporous silica (MS)-functionalized BNNS as novel nanovectors for CpG ODN delivery. Modification of BNNS with MS significantly improved the dispersity of BNNS and CpG ODN loading. BNNS@MS-NH2 exhibited no cytotoxicity and enhanced the delivery of CpG ODNs into macrophages. BNNS@MS-NH2/CpG ODN complexes triggered enhanced immunostimulation and induced higher amounts of cytokines. Most importantly, BNNS@MS-NH2/CpG ODN complexes induced bifurcated cytokines, which simultaneously simulated the secretion of IL-6, TNF-α and IFN-α. In contrast, CpG ODN and BNNS/CpG ODN complexes could not. The result of the Transwell plate assay suggested that BNNS@MS-NH2/CpG ODN complexes were more effective in inhibiting cancer cell growth. Taken together, our findings provide a promising strategy for enhancing CpG ODN-mediated cancer immunotherapy.

CpG-ODN Induces a Dose-Dependent Enrichment of Immunological Niches in the Spleen and Lungs of Neonatal Chicks That Correlates with the Protective Immunity againstEscherichia coli

“…The formulation of CpG-ODN with nanoparticles further improves the immune protective effect [30,33,34]. A recent study using boron nitride nanospheres functionalized with mesoporous silica demonstrated enhanced the delivery of CpG ODNs into macrophages that induced higher amounts of cytokines without cytotoxicity [47]. Previous studies suggested that enhanced expression of cytokines and chemokines [34,35] and increased cellular functions, such as the increase in heterophil degranulation and oxidative burst [48], play important roles in CpG-ODNinduced protection in chickens.…”

Palladium-based nanomaterials for cancer imaging and therapy

“…The integration of PTT with immunetherapy involving the incorporation of photothermal agents with immunomodulatory agents has brought some inspiring results 74 , 93 . Enhanced anti-cancer effects have been successfully obtained by the combination of photothermal agents and immune checkpoint blockades 94 and immunoadjuvants 95 - 97 . Recently, Pd NSs were reported as carriers of immunoadjuvant CpG oligodeoxynucleotides by our group 98 .…”

<p>Hexagonal Boron Nitrides (White Graphene): A Promising Method for Cancer Drug Delivery</p>

“…HydroxylationHydrogel composite[10]5. CpG oligodeoxynucleotidesGene therapy[22,23]6. Pd and copper (II) phthalocyaninePhototherapy[11,19]2.B 24 N 24 1.…”

“…At the same time, the BNNT@mesoporous silica hydrides for controllable surface zeta potential materials have shown higher suspension ability that facilitated intracellular endocytosis of doxorubicin 21. Moreover, the BNNTs encapsulated drug (curcumin) has found to efficient cellular uptake ability and in vitro release potentiality, which associated predictable anti-inflammatory effects of curcumin 22. Another study provided new insight towards the promising application of adenine-functionalized macromer (A-PPG) with the h-BN system in controlled release drug delivery systems.…”