Issue 8, 2022

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

Abstract

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.

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

Supplementary files

Article information

Article type
Communication
Submitted
19 5 2022
Accepted
07 6 2022
First published
08 6 2022
This article is Open Access
Creative Commons BY license

Nanoscale Horiz., 2022,7, 908-915

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

N. Hüppe, J. Schunke, M. Fichter, V. Mailänder, F. R. Wurm and K. Landfester, Nanoscale Horiz., 2022, 7, 908 DOI: 10.1039/D2NH00243D

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