Self-Assembly as a Molecular Strategy to Improve Immunotherapy

• DOI: 10.1021/acs.accounts.0c00438
• Publication Date: 2020-10-19T18:33:24Z
• Authors: Eugene Froimchuk; Sean T. Carey; Camilla Edwards; Christopher M. Je...
• Keywords: 0301 basic medicine; Static Electricity; Nanofibers; Biocompatible Materials; Hydrogen Bonding; Autoimmune Diseases; 3. Good health; Mice; 03 medical and health sciences; Adjuvants, Immunologic; Neoplasms; Animals; Humans; Immunotherapy; Antigens; Peptides; Hydrophobic and Hydrophilic Interactions; Micelles

ConspectusImmunotherapies harness an individual's immune system to battle diseases such as cancer and autoimmunity. During cancer, the often fails detect destroy cancerous cells, whereas during autoimmune disease, mistakenly attacks self-tissue. Immunotherapies can help guide more effective responses in these settings, evidenced by recent advances with monoclonal antibodies adoptive cell therapies. However, despite transformative gains of immunotherapies for patients, many therapies are not curative, work only a small subset lack specificity distinguishing between healthy diseased which cause severe side effects. From this perspective, self-assembled biomaterials promising technologies that could address some limitations facing immunotherapies. For example, self-assembly allows precision control over combination relative concentration cues directed cargo display densities. These capabilities support selectivity potency decrease off-target effects enable modular or personalized The underlying forces driving most systems aqueous solution result from hydrophobic interactions charge polarity. In Account, we highlight how being used self-assemble disease.Hydrophobic create range intricate structures, including peptide nanofibers, nanogels, micelle-like particles, vivo assemblies protein carriers. Certain nanofibers domains uniquely benefit ability elicit without additional stimulatory signals. This feature reduce nonspecific inflammation but may also limit nanofiber's application because their inherent properties. Micelle-like particles have been developed incorporate tumor-specific antigens mouse models cancer. Key observations revealed both total dose antigen density per particle impact response efficacy developments benchmarks reveal design principles engineering specific immunotherapies.There has extensive develop platforms using electrostatic drive assembly oppositely charged strategies tune biophysical components altering ratio cationic anionic formulation, charge. Using layer-by-layer method, our lab hollow capsules composed entirely signals disease models. platform allowed 100% immunotherapy be completely prevents onset model multiple sclerosis. Layer-by-layer coat microneedle patches target cells dermal layer. As alternative assembly, one step achieved mixing solution. Additional approaches created molecular structures leverage hydrogen bonding self-assembly. creativity engineered led key insights future aspects require further study. challenge now remains utilize push development new immunotherapeutics into clinical settings.