Reduction-Sensitive Protein Nanogels Enhance Uptake of Model and Tumor Lysate Antigens In Vitro by Mouse- and Human-Derived Dendritic Cells

Abstract

Peptides and proteins represent an emerging class of powerful therapeutics. Peptide and protein nanogels are attractive carriers for the transport and delivery of biologically active peptides and proteins because they allow essentially quantitative encapsulation of these biologics. One interesting field of use of peptide and protein nanogels is the transport of antigens and adjuvants in cancer immunotherapy. This study demonstrates the use of reduction-sensitive protein nanogels for the delivery of ovalbumin and oxidized tumor lysate-based antigens to mouse and human-donor-derived dendritic cells. Challenging mouse-derived and human dendritic cells with reduction-sensitive ovalbumin nanogels was found to significantly enhance antigen uptake as compared to the use of the corresponding free protein antigen. The experiments with mouse-derived dendritic cells further showed that the administration of ovalbumin in the form of reduction-sensitive nanogels enhanced dendritic cell maturation as well as the presentation of the SIINFEKL epitope as compared to experiments that use free ovalbumin. In addition to ovalbumin as a model antigen, the feasibility of reduction-sensitive nanogels was also demonstrated for the delivery of oxidized, whole tumor lysate-based cancer antigens. In experiments with dendritic cells harvested from human donors, dendritic cell uptake of the oxidized tumor lysate antigen was significantly enhanced in experiments that used oxidized tumor lysate nanogels as compared to the free antigen.

Biopolymer-Based Nanogel Approach in Drug Delivery: Basic Concept and Current Developments

“…It has been established that using nanosized formulations is a viable method for resolving some of these issues. Peptide and protein nanogels are especially promising because they make it possible to create nanosized formulations of these biologics with practically measurable encapsulation efficiency [ 14 , 163 , 164 , 165 , 166 ]. In the context of cancer immunotherapy, peptide/protein nanogels have also been investigated as carriers for the delivery of antigens and adjuvants [ 167 ].…”

“…Peptide/protein nanogels that include intermolecular disulfide bonds are particularly intriguing. Because of the disulfide crosslinks’ reduced sensitivity and cleavage upon exposure to the intracellular environment, these nanogels are appealing [ 166 ].…”

Biopolymer-Based Nanogel Approach in Drug Delivery: Basic Concept and Current Developments

“…It has been established that using nanosized formulations is a viable method for resolving some of these issues. Peptide and protein nanogels are especially promising because they make it possible to create nanosized formulations of these biologics with practically measurable encapsulation efficiency [14,[153][154][155][156]. In the context of cancer immunotherapy, peptide/protein nanogels have also been investigated as carriers for the delivery of antigens and adjuvants [157].…”

“…Peptide/protein nanogels that include intermolecular disulfide bonds are particularly intriguing. Because to the disulfide cross-links' reduced sensitivity and cleavage upon exposure to the intracellular environment, these nanogels are appealing [156].…”

Bioengineered nanogels for cancer immunotherapy

“…242 In addition to the delivery of OVA, the reduction-responsive nanogel could also be used for the delivery of oxidized tumour lysate (OxTL)-based antigens, enhancing the internalization of DCs. 243 Encouraged by these findings, Lobato et al prepared mannan-modified pH-responsive P (HEMA-co-MAA) nanogels as carriers for the delivery of OVA; the surface modification of mannan enhanced macrophage internalization, increased the expression of related CD40, and promoted the delivery of the antigen to APCs. 244 In another study, Umeki et al further verified that the DNA nanogel significantly improved antigen presentation in DCs wrapped with OVA and CpG oligodeoxynucleotides (ODNs).…”