Dendrimer nanocarriers for targeted co-delivery of MiR-146b-3p and 5-ALA to synergistic photodynamic therapy in secondary hyperparathyroidism

The combination of photodynamic therapy (PDT) and gene therapy is a viable therapeutic approach for the management of secondary hyperparathyroidism (SHPT). Nevertheless, the effective delivery of photosensitizers or nucleotide drugs remains a crucial limitation in achieving therapeutic efficacy. MiR-146b-3p directly targeted BCL2, and its overexpression enhanced the antiproliferative, proautophagic, and proapoptotic effects during 5-aminolevulinic acid (5-ALA)-mediated PDT in this study. Herein, we investigated the potential of codelivering 5-ALA and miR-146b-3p to SHPT primary cells via polyamidoamine (PAMAM) and achieving enhanced therapeutic efficacy relative to that of monotreatment. The fabrication of the PAMAM-based 5-ALA and miR-146b-3p dual-delivery system (5-ALA@PAMAM/miR) involved the use of covalent condensation reactions and electrostatic self-assembly. The nanoparticles were characterized by various analytical techniques, including transmission electron microscopy (TEM), zeta potential measurements, and size measurements. Fluorescence and confocal laser scanning microscopy demonstrated a greater degree of cellular uptake of nanoparticles. Moreover, the synthesized nanoparticles considerably enhanced the effectiveness of PDT without systemic toxicity both in vitro and in vivo. Overall, the nanocarrier-gene-photosensitizer coloaded system is a promising platform for the efficient simultaneous delivery of miR-146b-3p and 5-ALA and achieves synergistic therapeutic effects.