Implantable fibrous ‘patch’ enabling preclinical chemo-photothermal tumor therapy

Abstract

Localized drug delivery systems (LDDSs), in the forms of fibers or hydrogel, have emerged as an alternative approach for effective cancer treatment, but suffer challenges in the limited efficacy originated from sole therapeutic functionality. Herein, a multifunctional LDDS, showing feasibility for minimally-invasive implantation, was designed and synthesized for on-site chemo-photothermal synergistic therapy. In this system, polydopamine (PDA) nanoparticles, loaded with doxorubicin (DOX), were assembled at the surface of electrospun PCL-gelatin (PG) fibers (PG@PDA-DOX). The composite PG@PDA-DOX nanofibers could effectively transform NIR light into heat and present excellent photostability. In addition, low pH and NIR irradiation enabled remarkably accelerated DOX release. The in vitro study of PG@PDA-DOX fibers showed effective anti-cancer effect with irradiation of 808 nm NIR by inducing cell apoptosis and suppressing cell proliferation. The in vivo study, by implanting PG@PDA-DOX nanofibers in the patient derived xenograft (PDX) model via minimally-invasive surgery, presented that the composite fibers can effectively inhabit tumor growth by the combined chemo-photothermal effect without clear systematic side-effects. This study has therefore demonstrated a minimally-invasive platform, in a fibrous mesh form, with both high therapeutic efficacy and considerable potential in clinical translation for liver cancer treatment.