A scalable on-demand platform to assemble base nanocarriers for combination cancer therapy

Chemophototherapy is an advanced cancer therapeutic that uses photothermal nanocarriers (NCs) responsive to near-infrared (NIR) light. For the past decade, chemophototherapy has been investigated intensively for clinical translation, and continuous-flow production of biofunctional compounds (NCs, drugs, probes, nanocomposites) has received increasing attention for future therapeutics. However, in situ supply of a stimuli-responsive inorganic core and subsequent tight drug loading on the core are challenging tasks in the practical use of on-demand nanomedicines. Thus, in this study, we designed and evaluated both in vitro and in vivo models of an aero-hydro-aero single-pass production system for chemophotothermally active NCs. We prepare tightly-drug-loadable cores (titanium peroxide [yTiO2] nanovesicles [NVs]) using hydrogen flame pyrolysis of vaporized TiCl4 (aero) and successive ultrasonic H2O2 treatment (hydro). The NVs formed were incorporated with graphene oxide (GO), doxorubicin (D), and polyethylene glycol (P) in a spray to form GO-yTiO2@DP NCs (aero). The NVs' tight DP loading and endothermic effect induced greater, sustained D release and tumor-selective distribution, even for hyperthermic activity. The results showed the route developed may be a stepping stone to scalable, reconfigurable production for on-demand chemophotothermal therapeutics.