Self-Stabilized Supramolecular Assemblies Constructed from PEGylated Dendritic Peptide Conjugate for Augmenting Tumor Retention and Therapy

Supramolecular self-assemblies of dendritic peptides with well-organized nanostructures have great potential as multifunctional biomaterials, yet the complex self-assembly mechanism hampers their wide exploration. Herein, a self-stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate (PEG-dendritic peptide-pyropheophorbide a, PDPP), for augmenting tumor retention and therapy, is reported. The supramolecular self-assembly process of PDPP is concentration-dependent with multiple morphologies. By tailoring the concentration of PDPP, the supramolecular self-assembly is driven by noncovalent interactions to form a variety of SSAs (unimolecular micelles, oligomeric aggregates, and multi-aggregates) with different sizes from nanometer to micrometer. SSAs at 100 nm with a spherical shape possess extremely high stability to prolong blood circulation about 4.8-fold higher than pyropheophorbide a (Ppa), and enhance tumor retention about eight-fold higher than Ppa on day 5 after injection, which leads to greatly boosting the in vivo photodynamic therapeutic efficiency. RNA-seq demonstrates that these effects of SSAs are related to the inhibition of MET-PI3K-Akt pathway. Overall, the supramolecular self-assembly mechanism for the synthetic PEGylated dendritic peptide conjugate sheds new light on the development of supramolecular assemblies for tumor therapy.

Automated summary

The self-stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate shows potential for enhancing tumor retention and therapy. The concentration-dependent supramolecular self-assembly of PDPP forms various SSAs with different sizes and stability, leading to significantly improved in vivo photodynamic therapeutic efficiency.