Aerosol additive manufacturing of multi-component supraparticles for Fenton reaction-assisted multi-modal anticancer treatment

Nanoscale supraparticles have attracted considerable interest in cancer therapeutics and diagnostics because of the affordable structures that can be assembled for a stimulus response and the loading of active compounds for combinatorial theranostics. These nanostructures are usually constructed by balancing interparticle forces be-tween colloidal particles during thermodynamics-controlled growth. On the other hand, there are no relevant studies for assembling cancer theranostic supraparticles in an aerosol state, even though nanoparticles in that state have three orders of magnitude greater diffusional behavior for thermal collision between the particles compared to those in the aqueous state, as well as the limited numbers in separation and purification steps are required in aerosol processing. Aerosol additive manufacturing is designed using electrically operable devices as a digitizable platform for the spontaneous assembly of multi-component supraparticles in a continuous medium, which does not require special reaction conditions and complex controls for the desired assembly. Aggregates from electrostatic interactions between the oppositely charged Fe (Zn or Fe-Zn) and Cu constituent particles were inserted within 1-hexanethiol-docetaxel (DTX)-bovine serum albumin (BSA) mixture droplets for photo -induced thiolation of the outermost Cu particles and subsequent co-aggregation with DTX-BSA to form Fe(Zn or Fe-Zn)CuS@DTX-BSA supraparticles in a single-pass gas flow. The resulting supraparticles were used to examine the combinatorial anticancer effects in both in vitro and in vivo models, and anti-programmed death-ligand 1 antibodies were added to validate chemo-chemodynamic-photothermal-immuno combination therapeutics with no systemic toxicity.