ABSTRACT
Low-fouling hydrogels with tunable degradation rates and biochemical environments have the potential to improve adoptive cell therapies for cancer immunotherapy and regenerative medicine. To this end, we developed in situ gelling hydrogels from low-fouling poly(carboxybetaine-co-maleimide) (pCBM) random copolymers and thiolated hyaluronic acid (HA-SH). pCBM-HA hydrogel enzymatic degradation rates were tuned 5 fold by altering pCBM composition (4, 11, and 16 maleimide mol%) and 2.3 fold by HA-SH concentration (1-2 wt%). pCBM-HA gels were low-fouling towards bovine serum albumin (BSA; adsorbed â¼20 µg cm-2) and resisted fibroblast adhesion. To control pCBM-HA bioactivity, the cell adhesive peptide CGRGDS was immobilized on pCBM to promote fibroblast adhesion (39% decrease in circularity), which increased metabolic activity by â¼50%. pCBM-HA modified with CGRGDS enhanced the metabolic activity of encapsulated T cells by â¼21% compared to gels without HA, indicating their potential for immunotherapies. Low-fouling pCBM-HA hydrogels provide a vehicle with tunable degradation rates and biochemical environments for encapsulation applications in cell adoptive therapies.
Subject(s)
Betaine/chemistry , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Regenerative Medicine/methods , Tissue Engineering/methods , Acrylamides/chemistry , Adsorption , Animals , Cell Adhesion , Cell Encapsulation , Cell Survival , Cells, Cultured , Fibroblasts/metabolism , Immunotherapy , Leukocytes, Mononuclear/cytology , Materials Testing , Mice , NIH 3T3 Cells , Peptides/chemistry , Polymers , Serum Albumin, Bovine/chemistry , T-Lymphocytes/cytology , Tissue Engineering/instrumentationABSTRACT
Antibodies are a growing class of cancer immunotherapeutics that facilitate immune-cell-mediated killing of tumors. However, the efficacy and safety of immunotherapeutics are limited by transport barriers and poor tumor uptake, which lead to high systemic concentrations and potentially fatal side effects. To increase tumor antibody immunotherapeutic concentrations while decreasing systemic concentrations, local delivery vehicles for sustained antibody release are being developed. The focus of this review is to define the material properties required for implantable controlled antibody delivery and highlight the controlled-release strategies that are applicable to antibody immunotherapeutics.
