Hybrid nanoparticle-immune cell conjugates for augmented anticancer efficacy

Abstract

Cell-based therapies have become a powerful modality in cancer immunotherapy due to their innate cytotoxicity and ability to recognize tumor cells independently of antigen presentation. Among these, CAR-T and CAR-NK cells have shown promising anticancer effects in preclinical studies. In parallel, cell surface engineering using nanoparticles or biomaterials has emerged as a complementary strategy to modulate immune cell functions. Techniques such as hydrophobic insertion, covalent conjugation, glycoengineering, orthogonal chemistry, and host–guest interactions enable the presentation of ligands or immunomodulators directly on the cell surface. These nanoparticle–cell conjugates (NCC) allow for programmable interactions, controlled release, and enhanced tumor targeting. However, current conjugation methods often involve complex chemistries that may impair cell viability or are limited by cell-specific ligand–receptor interactions. This review outlines key aspects of NCC development: (1) nanoparticle design criteria, (2) NCC strategies, (3) limitations of direct conjugation, and (4) the role of AI in designing advanced cell-based therapies. Overall, NCC expands the therapeutic toolkit and offers a modular alternative to genetic engineering in next-generation cancer immunotherapy. © 2025 Elsevier B.V., All rights reserved.