On-demand drug release and hyperthermia therapy applications of thermoresponsive poly-(NIPAAm-co-HMAAm)/polyurethane core-shell nanofiber mat on non-vascular.

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On-demand drug release and hyperthermia therapy applications of thermoresponsive poly-(NIPAAm-co-HMAAm)/polyurethane core-shell nanofiber mat on non-vascular nitinol stents Ludwig Erik Aguilar, MSc, Amin GhavamiNejad, PhD, Chan Hee Park, PhD, Cheol Sang Kim, PhD Nanomedicine: Nanotechnology, Biology and Medicine Volume 13, Issue 2, Pages 527-538 (February 2017) DOI: 10.1016/j.nano.2016.12.012 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Schematics of (A) radical polymerization of NIPAAm and HMAAm monomers to poly(NIPAAm-co-HMAAm) and thermal crosslinking reaction. (B) Electrospinning process of the core-shell nanofiber mats on the nitinol stents. (C) Order of polymeric coating layer on to the nitinol stent. Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 FESEM images of the nanofibers, (A) pure PU, (B) p-NP-HM 9:1, (C) p-NP-HM 8:2 (D) PU/Composite+drugs, (E) Composite electrospun fibers on 60 mm nitinol stent samples, (F) nanofiber diameter survey using imageJ software. Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 3 TEM images of core-shell nanofibers, (A) 9:1 p-NP-HM, (B) 8:2 p-NP-HM. Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 4 Mechanical strength test of drug loaded nanofiber composites compared to pure PU and pure p-NP-HM. (A) Young's Modulus, (B) Tensile Strength, (C) Percentage strain, (D) Stress vs Strain. * indicates statistical significance (P<0.05), ** indicates statistical significance (P<0.01) (one way ANOVA post hoc Tukey test). Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 5 In vitro drug release profile of both PTX and 5-FU from the core-shell nanofiber composite mat at different temperature and time points and cycles. Each temperature point was maintained for 10 min. Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 6 In vitro biocompatibility test using CCK8 assay and confocal images of NIH 3T3 fibroblast cells. (A) Biocompatibility test on the polymer component. (B) Biocompatibility test on Composite+drugs vs Bare PTX and 5-FU on different doses (Dose 1, 800 μg; Dose 2, 400 μg; Dose 3, 1.8 mg PTX, 1.8 mg 5-FU). The data are reported as the mean±standard deviation (n=5 and * indicates statistical significance (P<0.05), ** indicates statistical significance (P<0.01) (one way ANOVA post hoc Tukey test)). Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 7 (A) Cell proliferation Index of ESO26 and OE21 human esophageal cancer cell line. The cell proliferation index was calculated using ND/ND1=1, where ND=cell number on day D and ND1=1=cell number on day 1 (broken red line indicates the time when AMF was switched ON). (B) Live/Dead Assay using Flow cytometry (FACS). Cells stained using C12-resazurin red and Sytox® green stain, events counted=10,000. Treatment Group Abbreviations; HHRx, Hyperthermia (45 °C) with dual drug release; LHRx, hyperthermia (40 °C) with single drug release; H, Hyperthermia (45 °C); HfreeRx, Hyperthermia (45 °C) with free combination drugs; freeRx, Free combination drugs. Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 8 Confocal images of (A) ESO26 cell line live/dead staining and (B) OE21 cell line DAPI and Rhodamine stains. Treatment Group Abbreviations; HHRx, Hyperthermia (45 °C) with dual drug release; LHRx, hyperthermia (40 °C) with single drug release; H, Hyperthermia (45 °C); HfreeRx, Hyperthermia (45 °C) with free combination drugs; freeRx, Free combination drugs. Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions

Nanomedicine: Nanotechnology, Biology and Medicine 2017 13, 527-538DOI: (10.1016/j.nano.2016.12.012) Copyright © 2016 Elsevier Inc. Terms and Conditions