Photoresponsive Polypeptide-Glycosylated Dendron Amphiphiles: UV-Triggered Polymersomes, OVA Release, and In Vitro Enhanced Uptake and Immune Response.

Efficient therapeuic proteins' delivery into mammalian cells and subcellular transport (e.g., fast escape from endolysosomes into cytoplasm) are two key biological barriers that need to be overcome for antigen-based immunotherapy and related biomedical applications. For those purposes, we designed a novel kind of photoresponsive polypeptide-glycosylated poly(amidoamine) (PAMAM) dendron amphiphiles (PGDAs), and their synthesis, UV-responsive self-assembly, and triggered ovalbumin (OVA) release have been fully investigated. The highly anisotropic PGDA4 with a glycosylated second-generation PAMAM dendron self-assembled into stable polypeptide vesicles (polymersomes) within 20-50 wt % water, which exhibited UV-responsive reassembly, dynamic binding with a lectin of concanavalin A, and an accelerated OVA release in vitro. Moreover, upon 365 nm UV irradiation, the self-assembled polymersomes of those glycopolypeptides were transformed into micellar aggregates in aqueous solution at pH 7.4 but disassembled completely at pH 5. The OVA-loaded polymersomes could efficiently deliver OVA into RAW264.7 cells and achieve enhanced endolysosomes escape upon UV irradiation, as revealed by flow cytometry and confocal laser scanning microscopy (CLSM). Furthermore, the enzyme-linked immunosorbent assay (ELISA) showed that the blank sugar-coated polypeptidosomes activated a high level of tumor necrosis factor α (TNF-α) of 468 pg/mL, playing a better role of immune adjuvant for activating the macrophages. Upon the UV irradiation with a dose of 3 J/cm2, the OVA-loaded polymersomes could further stimulate RAW264.7 and enhance the TNF-α level by about 45%. Consequently, this work provides a versatile platform to construct photosensitive and sugar-coated polymersomes of glycopolypeptides that have potential applications for protein delivery, immune adjuvant, and antigen-based immunotherapy.