Last modified: 2019-06-15
Abstract
Background: Chemo-phototherapy employing anti-cancer drugs and a photothermal agent responsive to near-infrared (NIR) light have been intensively investigated for clinical translation and continuous-flow production of biofunctional compounds [nanocarriers (NCs), drugs, probes, nanocomposites] to increase the treatment efficacy of anticancer drugs.
Objectives: 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 chemo photothermally active NCs.
Methods: In this study, we have employed an aero-hydro-aero approach for in situ self-assembly of titanium peroxide [yTiO2nanovesicles using hydrogen flame pyrolysis of vaporized TiCl4: aero, successive ultrasonic H2O2 treatment: hydro] and graphene oxide (GO)-doxorubicin (D)-polyethylene glycol (P) mixture in a spray (aero) to form GO-yTiO2@DP NC without process interruptions. Here, yTiO2, which acts as a photothermal agent, tightly loads DP (a model drug with stealth coating) during the single-pass process through capillary suction (from interparticle voids between primary yTiO2) with adsorption and electrostatic attraction because of its net negative surface charges. Thus prepared NCs were directly sampled from the reacted gas flow, dispersed in buffered saline, and assessed in terms of in vitro and in vivo cancer chemophototherapy.
Results: The prepared NCs showed tight drug loading, enhanced stability and the endothermic effect induced greater sustained D release profile as well as enhanced cytotoxicity attributable to combined chemo-photothermal therapy.
Conclusion: A continuous, scalable route was developed to produce tightly-drug-loadable photoresponsive NCs via single-pass aero–hydro–aero assembly of GO-yTiO2@DP NCs to demonstrate its efficacy in chemo-phototherapy. Tightly drug-loadable and photostimulable NCs, may not only offer a reliable base material for chemo phototherapy but also provide significant insights into the scalability of multi-biofunctional NCs for built-to-order therapeutics.