Stimuli‐Responsive Biomaterials for Vaccines and Immunotherapeutic Applications

Abstract

The immune system is the key target for vaccines and immunotherapeutic approaches aimed at blunting infectious diseases, cancer, autoimmunity, and implant rejection. However, systemwide immunomodulation is undesirable due to the severe side effects that typically accompany such strategies. In order to circumvent these undesired, harmful effects, scientists have turned to tailorable biomaterials that can achieve localized, potent release of immune‐modulating agents. Specifically, “stimuli‐responsive” biomaterials hold a strong promise for delivery of immunotherapeutic agents to the disease site or disease‐relevant tissues with high spatial and temporal accuracy. This review provides an overview of stimuli‐responsive biomaterials used for targeted immunomodulation. Stimuli‐responsive or “environmentally responsive” materials are customized to specifically react to changes in pH, temperature, enzymes, redox environment, photo‐stimulation, molecule‐binding, magnetic fields, ultrasound‐stimulation, and electric fields. Moreover, the latest generation of this class of materials incorporates elements that allow for response to multiple stimuli. These developments, and other stimuli‐responsive materials that are on the horizon, are discussed in the context of controlling immune responses.

Biomaterial-based immunotherapeutic strategies for rheumatoid arthritis

“…The EPR effect describes a phenomenon where nanoparticles tend to accumulate within tissues with leaky vasculature, such as sites of inflammation, or within tumors [85]. Membrane surfaces of the nanocarriers can also be customized through ligation of antibodies, peptides, and receptors, or incorporation of environmentally sensitive bonds [86] to facilitate active targeting of specific tissue compartments [84]. Nanocarriers can also function as drug depots with programmable release kinetics [84].…”

“…Moreover, the potential for customizability is vast. Altering the material used for fabrication of NPs and MPs can bestow dynamic characteristics to the drug carrier system that allows for targeting of different environmental cues or specific disease states [86], or even potentially conferring intrinsic characteristics into the particle itself [102]. For example, many gut-derived molecules exert immunosuppressive effects and are garnering interest for their potential to be fabricated into particles that possess tolerance-inducing effects [102], and poly-conjugated aspirin particles have been used to confer innate anti-thrombus activity into the particle itself [103].…”

“…For example, many gut-derived molecules exert immunosuppressive effects and are garnering interest for their potential to be fabricated into particles that possess tolerance-inducing effects [102], and poly-conjugated aspirin particles have been used to confer innate anti-thrombus activity into the particle itself [103]. Additionally, particles that incorporate pH-sensitive bonds such as aliphatic monomers incorporating cleavable acetal links can facilitate preferential cargo delivery into specific environments where the pH is acidic [86]. Other environmental attributes can be targeted for precision-based delivery of the payload through incorporation of bonds that are sensitive to various environmental cues, such as temperature, enzymes, light, and hypoxia [86].…”

“…Additionally, particles that incorporate pH-sensitive bonds such as aliphatic monomers incorporating cleavable acetal links can facilitate preferential cargo delivery into specific environments where the pH is acidic [86]. Other environmental attributes can be targeted for precision-based delivery of the payload through incorporation of bonds that are sensitive to various environmental cues, such as temperature, enzymes, light, and hypoxia [86]. A comprehensive review encompassing many different stimulus-responsive biomaterials can be found here [86].…”

“…Other environmental attributes can be targeted for precision-based delivery of the payload through incorporation of bonds that are sensitive to various environmental cues, such as temperature, enzymes, light, and hypoxia [86]. A comprehensive review encompassing many different stimulus-responsive biomaterials can be found here [86]. Additionally, the membrane surface of NPs and MPs can be functionalized with a variety of ligands, such as peptides, receptors, or antibodies, further allowing precise delivery to specific immune cell subsets or tissues [83,84,104].…”