Plasmonic semi shells derived from simultaneous in situ gold growth and anisotropic acid etching of ZIF-8 for photothermal ablation of metastatic breast tumor

Abstract A rapid colloidal synthetic protocol for PEGylated semi shell (SS) fabrication using nano metal-organic framework, ZIF-8 as a sacrificial template is reported. The mechanism of semi shell formation was found to be simultaneous facet specific anisotropic chemical etching of rhombic dodecahedral ZIF-8 and heterogenous nucleation & growth of gold. The SS possesses a strong localized surface plasmon resonance in the near-infrared region, which is retained after surface passivation with polyethylene glycol and subsequent cryopreservation for extended shelf-life. Freshly reconstituted PEGylated SS was found to be hemocompatible & biocompatible under in vitro conditions as well as safe & non-toxic in healthy C57BL/6 mice post intravenous administration for up to 28 days. The PEGylated SS displayed significant photothermal efficiency of ~ 37% with 808 nm laser irradiation. Preclinical assessment of intra-tumoral photothermal efficacy indicated complete remission of primary breast tumor mass with insignificant metastasis to vital organs in 4T1 FL2 tumor bearing CD1 nude mice. Further, PEGylated SS mediated photothermal therapy also yielded morbidity free survival of 75% in a syngeneic 4T1 breast tumor model for up to 90 days, indicating their potential to significantly improve outcomes in advanced breast tumors.