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Abstract Peptides are an emerging class of biologics for cancer immunotherapy; however, their clinical translation is hindered by poor binding kinetics, bioavailability, and short plasma half‐life compared to their corresponding antibodies. Nanoparticles present potential solutions but face scale‐up difficulties due to complexity. Here, a translatable, modular nanoparticle scaffold is presented for peptide‐based immune checkpoint inhibitors (ICIs). This platform is based on a simple structure of generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers conjugated with engineered peptides (dendrimer‐peptide conjugates, DPCs). DPCs functionalized with multiple copies of a programmed death‐ligand 1 (PD‐L1)‐binding peptide exhibited significantly enhanced avidity‐based binding kinetics and in vitro specificity, in addition to the substantially prolonged plasma half‐life in vivo. Notably, a series of in vivo experiments revealed that DPCs displayed selective tumor accumulation and high efficacy, without apparent toxicity, when applied to a syngeneic mouse model bearing mouse oral carcinoma (MOC1) tumors. The results indicate that the DPC platform significantly improves the antagonistic effect and in vivo behaviors of the PD‐L1‐binding peptides, which can be potentially applied to virtually any peptide‐based ICIs. The DPC platform's simplicity and modular nature will likely increase the potential of its clinical translation and ultimately enable precision/personalized cancer immunotherapy. 

Dendrimers and dendritic NPs are emerging as potential nanoplatforms for cancer immunotherapy. This minireview provides an updated overview of dendrimer conjugates, dendritic hybrids, and dendron-based copolymers for targeted therapy.