Precision Wormlike Nanoadjuvant Governs Potency of Vaccination

Abstract

It remains unclear how the precise length of onedimensional nanovehicles influences the characters of vaccination.Here, a unimolecular nanovehicle with tailored size and aspect ratio (AR) is applied to deliver CpG oligodeoxynucleotide, a Toll-like receptor (TLR) 9 agonist, as an adjuvant of recombinant hepatitis B virus surface antigen (rHBsAg), for treating chronic hepatitis B (CHB). Cationic nanovehicles with fixed width (ca. 45 nm) but varied length (46 nm−180 nm), AR from 1 to 4, are prepared through controlled polymerization and are loaded with CpG by electrostatic interaction. We reveal that the nanoadjuvant with AR = 2 shows the highest retention in proximal lymph nodes. Importantly, it is more easily internalized into antigen-presenting cells and accumulates in the late endosome, where TLR9 is located. Such a nanoadjuvant exhibits the strongest immune response with rHBsAg to clear the hepatitis B virus in the CHB mouse model, showing that the AR of nanovehicles governs the efficiency of vaccination.

Impact of Zwitterionic Polymers on the Tumor Permeability of Molecular Bottlebrush-Based Nanoparticles

“…Additionally, the MBs designed in this study are nanoparticles constructed by covalent bonding rather than self-assembly systems, indicating that it is not necessary to consider the potentially complicated issues mentioned in the micellar and metal nanoparticle systems. Based on these structural features, MBs composed of biocompatible polymers are suitable model polymeric nanoparticles for the comparison of their tissue permeability as well as a powerful building block for next-generation polymer-based nanomedicines. − Although there have been studies discussing the effect of the size and morphology of the nanoparticles coated with PEG on the tumor permeability, ,,,, we revealed the importance of zwitterionic nature in tumor penetration in addition to those particle characteristics. Furthermore, we demonstrated the improvement of tumor permeability of PEG-based nanoparticles by incorporating a small amount of zwitterionic betaine polymers.…”

Molecular polymer bottlebrushes in nanomedicine: therapeutic and diagnostic applications

“…(C) A core-shell MPB with cationic core is used to load a Toll-like receptor (TLR) 9 agonist and induce an immune response to the hepatitis B virus. Adapted with permission from Sun et al 112 showed lower cytotoxicity and higher transfection activity when compared to linear high molecular weight PDMAEMA or 25 kDa PEI.…”

“…with AR = 2) boosted immune responses and delivery outcomes in vivo. 112 This journal is © The Royal Society of Chemistry 2022 Chem. Commun., 2022, 58, 5683-5716 | 5711…”

“…5C). 114 The study not only investigated the delivery, but also the effect of carrier aspect ratio (AR) in delivering cargo to the lymph node to induce potent immune responses to the hepatitis B virus and treat chronic hepatitis B. MPBs of fixed width (45 nm) but varied length (46–180 nm) formed carriers with ARs of 1 to 4. Interestingly, AR = 2 showed the highest retention in proximal lymph nodes, preferential traffic kinetics and better cellular endocytosis in vivo compared to the other ARs.…”

Precision therapy through breaking the intracellular redox balance with an MOF-based hydrogel intelligent nanobot for enhancing ferroptosis and activating immunotherapy

“…Recent research reported that immune adjuvants TLR9 agonist CpG oligodeoxynucleotides (CpG-ODNs) could enhance antitumor immune responses to trigger a powerful systemic anti-tumor therapeutic effect. 28,29 As small RNAs, CpG-ODNs were impermeable to the cellular membrane, owing to unstable, relatively high molecular weight, and negatively charged character. Hence, the development of a secure delivery carrier of siRNA is especially important for tumor therapeutics.…”