Field-actuated antineoplastic potential of smart and versatile PEO–bPEI electrospun scaffold by multi-staged targeted co-delivery of magnetite nanoparticles and niclosamide–bPEI complexes

Abstract

Surgical removal of tumor mass is often followed by its recurrence at the same or a distant location by proliferation and metastasis of remnant cancer cells at the site of surgery. In order to circumvent such complications, we have designed a biocompatible smart stimuli responsive anti-cancer nanofiber patch which can effectively eliminate cancer cells and, at the same time, acts as physical barrier for cancer metastasis. In pursuit of this, in this work we fabricated a composite bPEI–PEO nanofiber scaffold loaded with folic acid functionalized octagonal magnetite nanoparticles (FA-bPEI@Fe₃O₄ NPs) and bPEI–niclosamide complexes and further evaluated its field responsive anticancer therapeutic efficacy. Highly magnetic FA-bPEI@Fe₃O₄ NPs impregnated within nanofiber renders them susceptible to partial disintegration by an external alternating magnetic field (AMF) and thereby enables them to attain on-demand stipulated release of FA-bPEI@Fe₃O₄ NPs and bPEI–niclosamide complexes. Upon release, free FA-bPEI@Fe₃O₄ NPs and niclosamide perpetrated cell death by instigating apoptosis and oxidative stress (in KB cells (FR+) and L132 cells (FR−)) which was subsequently investigated on a qualitative and quantitative basis in a time dependent manner by fluorescence microscopy and flow cytometry, and further corroborated with semi-quantitative RT-PCR analysis. In summary, the composite nanofiber fabricated herein can manifest stipulated on-demand release of diverse bioactive molecules solely under the influence of external AMF and thereby effectively attain the therapeutic perquisites of cancer prognosis exactly where and when needed.