Implantable Synergistic Tumor Therapapy Platform Based On Nanofiber

Part ?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 p H 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.Part ?Targeted drug delivery to tumor tissue and effective intracellular transportation are two crucial challenges remained for the current nanomedicine in cancer therapy.Herein,an implantable device consisting of hierarchical composite fibers was constructed for the localized synergistic chemo-/starvation therapy.In this hierarchical system,electrospun PCL/gelatin(PGH)nanofibers,loaded with hyaluronidase(HAase),serve as a matrix of multiple therapeutics for minimal invasive implantation.Mesoporous silica nanoparticles(MSNs)were loaded with glucose oxidase(GOx)followed by coverage of a p H-responsive polydopamine(PDA)coating.A hypoxia-activated prodrug,banoxantrone(AQ4N),were absorbed at the particle surface(MGPA).MGPA nanoparticles,which play a role as the transportation cargo of therapeutics into the cancer cells,were electrostatically assembled on the surface of PGH nanofibers(PGH@MGPA).Controllable liberation of MGPA nanoparticles from PGH nanofibers and subsequent cellular internalization were observed in the weak acidic tumor microenvironment.Meanwhile,HAase released from the PGH fibers can effectively decompose hyaluronan,a major component of extracellular matrix(ECM)in tumors,and thereby promote the cellular uptake of MGPA nanoparticles.GOx could exhaust glucose and O2 supply,following with starvation-induced aggravation of microenvironmental hypoxia,which further actived AQ4 N to toxic AQ4.In consequence,this hierarchical composite fibers presented remarkably enhanced inhibition of cancer cell growth both in vitro and in vivo.This study has therefore demonstrated a new concept,combining advantages of systematic and implantable drug delivery systems,in the therapeutic device for cancer therapy with high efficacy.