Fig. 11
(Reprinted from [270] with permission from the American Chemical Society)
Nano-immunotherapy against respiratory viral infection. A, B Stepwise synthesis of polymer–nanoparticle (PNP) hydrogels comprising TLR7/8a-functional nanoparticles. PNP hydrogels are formed when i poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA) nanoparticles (NPs) or TLR7/8a-conjugated PEG-PLA NPs are combined with ii dodecyl-modified hydroxypropylmethylcellulose (HPMC-C12). Vaccine cargo can be added to the aqueous NP solution before mixing, which yields complete encapsulation into the fabricated hydrogels. iii A homogeneous gel is easily achieved using an elbow mixer or a spatula. C Small molecular cargo, such as TLR7/8a, can be chemically attached to the hydrogels’ PEG-PLA NP structural motif to assure long-term delivery. D NHS coupling of alykyne functionality to TLR7/8a (I) followed by copper-catalyzed “click” coupling to azide-terminated PEGPLA (II) yields PEG-PLA with the TLR7/8a (purple) presenting on the hydrophilic PEG (blue) terminus of the block copolymer (III). This polymer is then nanoprecipitated into the water to form TLR7/8a-functional NPs. E Influenza hemagglutinin subunit vaccination induces a cellular response. (a) A 2 g dosage of hemagglutinin (HA) was delivered subcutaneously in either a PNP gel prepared with 10% TLR7/8a-conjugated nanoparticles (TLR7/8a-NP Gel) and 2% HPMC-C12, a bolus of AddaVax (formulated like MF59, the most powerful adjuvant used therapeutically for influenza), or Alum. F Anti-HA IgG titers in serum from day 14 to day 56 after a single HA injection in TLR7/8a-NP gel, TLR7/8a-Sol gel, AddaVax bolus, or Alum bolus. P values for TLR7/8a-NP gel vs. Alum (bottom, dark blue), TLR7/8a-Sol gel (middle, light blue), and AddaVax (top, orange) (n = 4 to 5). G Increased breadth of antibodies toward future influenza strains