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Impact of the conjugation of antibodies to the surfaces of polymer nanoparticles on the immune cell targeting abilities.

ABSTRACT: Antibodies have been widely used to provide targeting ability and to enhance bioactivity owing to their high specificity, availability, and diversity. Recent advances in biotechnology and nanotechnology permit site-specific engineering of antibodies and their conjugation to the surfaces of nanoparticles (NPs) in various orientations through chemical conjugations and physical adhesions. This study proposes the conjugation of poly(lactic-co-glycolic acid) (PLGA) NPs with antibodies by using two distinct methods, followed by a comparison between the cell-targeting efficiencies of both techniques. Full-length antibodies were conjugated to the PLGA-poly(ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) NPs through the conventional carbodiimide coupling reaction, and f(ab')₂ antibody fragments were conjugated to the PLGA-poly(ethylene glycol)-maleimide(PLGA-PEG-Mal) NPs through interactions between the f(ab')₂ fragment thiol groups and the maleimide located on the nanoparticle surface. The results demonstrate that the PLGA nanoparticles conjugated with the f(ab')₂ antibody fragments had a higher targeting efficiency in vitro and in vivo than that of the PLGA nanoparticles conjugated with the full-length antibodies. The results of this study can be built upon to design a delivery technique for drugs through biocompatible nanoparticles.

SUBMITTER: Lee NK

PROVIDER: S-EPMC8368787 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The reversible binding between a planar polymer layer functionalized by ligands and a planar cell surface containing different densities of mobile receptors has been studied by Monte Carlo simulations. Using the acceptance-ratio method, the distance-dependent profiles for the average number of ligands bound to receptors, the total free energy for the polymer layer-cell surface interaction and the interaction force were obtained. Four main design parameters for the polymer layer were considered: the degree of functionalization, chain degree of polymerization, polymer grafting density and the binding energy for the ligand-receptor interaction. We found that an increase in the degree of functionalization or in the absolute energy of ligand-receptor binding results in a larger number of ligands bound to the receptors, lower free energy, and stronger attractive force. Polymer layers composed of shorter chains were found to exhibit a deeper and narrower free energy profile and a larger attractive force, while longer tethers can interact with the cell surface at a larger and broader range of separation distances, in agreement with experimental observations. Our simulation results show that the increase in polymer grafting density from the mushroom to brush regime enhances the ligand availability and results in a stronger attractive force, increases the maximum binding distance, but exhibits a shallower free energy minimum due to the smaller tolerance to compression for polymer layers with high grafting density. We used two measures of the polymer layer binding affinity to the cell surface: the free energy minimum, related to the equilibrium binding constant and the fraction of bound ligands. We found that the polymer layers with a smaller chain length and grafting density, larger degree of functionalization, and larger absolute binding energy exhibit both a larger equilibrium binding constant to the cell surface and a larger average number of bound ligands, except for high binding energies when the maximum level of binding is reached independently of polymer length and grafting density. We showed that high binding specificity can be achieved by the polymer layers with intermediate ligand-receptor binding energies or an intermediate number of ligands, as a larger binding energy or number of ligands ensures a high binding affinity but lacks specificity while a smaller binding energy or number of ligands provides inadequate affinity. We found that the results for polymer layers with different properties follow a similar pattern when both high binding affinity to cells with high receptor density and high binding specificity are considered. As a result, the optimal design of the polymer layers can be achieved by using several different strategies, which are discussed.

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Impact of the conjugation of antibodies to the surfaces of polymer nanoparticles on the immune cell targeting abilities.

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