Multicomponent encapsulation into fully degradable protein nanocarriers via interfacial azide-alkyne click reaction in miniemulsion allows the co-delivery of immunotherapeutics

Encapsulation of multiple adjuvants along with antigens into nanocarriers allows a co-delivery to antigen-presenting cells for the synergistic induction of robust immune responses. However, loading cargoes of different molar masses, polarities, and solubilities in high efficiencies remains a challenge. Therefore, we developed a strategy to encapsulate a triple combination of the so-called adjuvants, i.e. with Resiquimod (R848), muramyl dipeptide (MDP) and polyinosinic-polycytidylic acid (Poly(I : C)) into human serum albumin (HSA) nanocarriers. The loading is conducted in situ while the nanocarrier is formed by an orthogonal and metal-free click reaction at the interface of an inverse miniemulsion. By this unique approach, high encapsulation efficiency without harming the cargo during the nanocarrier formation process and regardless of their physical properties is achieved, thus keeping their bioactivity. Furthermore, we demonstrated high control over the encapsulation efficiency and varying the amount of each cargo did not influence the efficiency of multicomponent encapsulation. Azide-modified HSA was crosslinked with hexanediol dipropiolate (HDDP) at the interface of a water-in-oil miniemulsion. Varying the crosslinker amount allowed us to tailor the density and degradation rates of the protein shell. Additional installation of disulfide bonds into the crosslinker created redox-responsive nanocarriers, which degraded both by protease and under reducing conditions with dithiothreitol. The prepared HSA nanocarriers were efficiently taken up by dendritic cells and exhibited an additive cell activation and maturation, exceeding the nanocarriers loaded with only a single drug. This general protocol allows the orthogonal and metal-free encapsulation of various drugs or adjuvants at defined concentrations into the protein nanocarriers

Defect engineering of polyethylene-like polyphosphoesters: Solid-state NMR characterization and surface chemistry of anisotropic polymer nanoplatelets

Anisotropic materials with very high aspect ratios, such as nanoplatelets, are an exciting class of materials due to their unique properties based on their unilamellar geometry. Controlling their size and surface-functionality is challenging and has only be achieved in some cases for synthetic polymers. We present a general approach to prepare polymer-nanoplatelets with control over the lateral size and basal functionality, by simple polycondensation of precisely spaced and functional phosphate groups in polyethylene-like polymers. Because of the relatively large size of the phosphate groups, they are expelled from the bulk crystal to the basal surface. This allows to control the chain-folding during crystallization, which we analyzed via solid-state NMR and TEM. Furthermore, we present chemistry “on the surface” of the platelets: the pendant ester group at the phosphate offers the possibility to introduce functional groups accessible for further chemical modification on the crystal surface. This is shown by introducing a 2-acetylthioethyl ester group and subsequently cleaving this 2-acetylthioethyl ester group to the free P–OH. Together, these results render polyethylene-like polyphosphoesters a versatile platform for soft-matter nanoplatelets as functional colloids

Edge effects in graphene nanostructures: II. Semiclassical theory of spectral fluctuations and quantum transport

We investigate the effect of different edge types on the statistical properties of both the energy spectrum of closed graphene billiards and the conductance of open graphene cavities in the semiclassical limit. To this end, we use the semiclassical Green's function for ballistic graphene flakes that we have derived in Reference 1. First we study the spectral two point correlation function, or more precisely its Fourier transform the spectral form factor, starting from the graphene version of Gutzwiller's trace formula for the oscillating part of the density of states. We calculate the two leading order contributions to the spectral form factor, paying particular attention to the influence of the edge characteristics of the system. Then we consider transport properties of open graphene cavities. We derive generic analytical expressions for the classical conductance, the weak localization correction, the size of the universal conductance fluctuations and the shot noise power of a ballistic graphene cavity. Again we focus on the effects of the edge structure. For both, the conductance and the spectral form factor, we find that edge induced pseudospin interference affects the results significantly. In particular intervalley coupling mediated through scattering from armchair edges is the key mechanism that governs the coherent quantum interference effects in ballistic graphene cavities