Short duration cancer treatment: inspired by a fast bio-resorbable smart nano-fiber device containing NIR lethal polydopamine nanospheres for effective chemo-photothermal cancer therapy

Abstract

Background: The objective of this study was to evaluate the efficacy of a combination of Photothermal therapy (PTT) and chemotherapy in a single nano-fiber platform containing lethal polydopamine nanopheres (PD NPs) for annihilation of CT 26 cancer cells.

Method: Polydioxanone (PDO) nanofiber containing PD and bortezomib (BTZ) was fabricated via electrospinning method. The content of BTZ and PD after optimization was 7% and 2.5% respectively with respect to PDO weight. PD NPs have absorption band in near-infrared (NIR) with resultant rapid heating capable of inducing cancer cell death. The samples was divided into three groups - PDO, PDO+PD, and PDO+PD-BTZ for analysis.

Results: In combined treatment, PDO nanofiber alone could not inhibit cancer cell growth as it neither contain PD or BTZ. However, PDO+PD fiber showed a cell viability of approximately 20% after 72 hr of treatment indicating minimal killing via hyperthermia. In the case of PDO composite fiber containing BTZ, the effect of NIR irradiation reduced the viability of cancer cells down to around 5% after 72 h showing the efficiency of combination therapy on cancer cells elimination. However, due to higher photothermal conversion that may negatively affect normal cells above 46°C, we have employed 1 s "OFF" and 2 s "ON" after initial 9 s continuous irradiation to maintain the temperature between 42 and 46°C over 3 mins of treatment using 2 W/cm²; 808 nm laser which resulted to similar cell death.

Conclusion: In this study, combination of PTT and chemotherapy treatment on CT 26 colon cancer cells within 3 min resulted in effective cell death in contrast to single treatment of either PTT and chemotherapy alone. Our results suggest that this nanofiber device with efficient heating and remote control drug delivery system can be useful and convenient in the future clinical application for localized cancer therapy.

Keywords: Bortezomib; chemotherapy; combination cancer therapy; electrospinning; electrospun nanofiber; local treatment; photothermal therapy; polydopamine nanospheres.

Figure 1

A schematic illustration from material fabrication to tumor ablation using a single hybrid nanofiber platform for synergistic anticancer treatment via simultaneous PTT and chemotherapy. Abbreviations: NIR, near-infrared; PTT, photothermal therapy.

Figure 2

Morphological changes in PDO nanofiber device. Notes: (A) PDO nanofiber. (B) PDO+PD. (C) PDO+PD after laser irradiation for 60 seconds. (D) PDO+PD after five cycles of laser irradiation at 60 seconds per cycle. (A¹) The smooth surface of PDO. (B¹) PDO+PD surface with visible particles finely distributed and marked with red arrow. (C¹) PDO+PD shows a gross surface of nanofiber with minimal fused intersections after 60 seconds of laser irradiation. (D¹) PDO+PD fiber surface with most of the intersection fused. Abbreviations: PD, polydopamine; PDO, polydioxanone.

Figure 3

DSC and degradation property of various composite fibers. Notes: (A) Variation in glass transition and other heating properties of various fibers. (B) Heat flow of various fiber mats. (C) Weight loss of PDO nanocomposites over 80 days in PBS (pH 7.4). Abbreviations: BTZ, bortezomib; DSC, differential scanning calorimeter; PD, polydopamine; PDO, polydioxanone; NIR, near-infrared; T_g, glass transition temperature; T_c, crystallization temperature; T_m, melting temperature; H_m, enthalpy of melting; H_c, enthalpy of crystallization.

Figure 4

Characterization of PD NPs and photothermal stability testing. Notes: (A) SEM image of PD NPs (inset – the magnified image of A). (B) A vial containing an aqueous suspension of various concentrations of PD (50, 100, 500, and 1,000 µg/mL). (C and D) Stability of PD NPs before and after five cycles of laser irradiation (2 W/cm²; 808 nm at 60 seconds per cycle). (E) Effect of concentration on the photothermal output of PD NPs at 60 seconds irradiation (808 nm; 2 W/cm²). (F) High precision thermal cycle by nonstop laser on–off switching on PDO composite fiber. The blue and red zones as indicated represent “on” and “off” modes, respectively. The sample was irradiated with 808 nm laser at the power of 2 W/cm² for 60 seconds (“on”) followed by natural cooling for 300 seconds (“off”). Abbreviations: PD NPs, polydopamine nanospheres; PDO, polydioxanone; SEM, scanning electron microscopy.

Figure 5

Laser-induced heating on different concentrations of PD NP solution and composite fiber. Notes: (A–D) Thermographic images of PD NP solution droplet (300 µL of 50, 100, 500, and 1,000 µg/mL, respectively) after NIR irradiation. (E) Digital image of fabricated nanofiber device (white – neat PDO fiber mat and brown – with PD NPs [3.8 mg/mL]) (F) Thermographic image was captured from respective Movie S1 showing PDO composite nanofiber device (0.005 mg) in 300 µL PBS. Power and wavelength of the NIR light used in this study were the same for all samples, that is, 2 W/cm² and 808 nm, respectively, for 60 seconds irradiation time. All images are screenshots captured from respective movies. Abbreviations: NIR, near-infrared; PD NPs, polydopamine nanospheres; PDO, polydioxanone.

Figure 6

(A) Fiber diameter distribution in the fabricated photothermal device. (B) Cell viability following treatment with various concentrations of PD NPs and using TCP as control after 48 hours culture. Note: Error bar represents SD of three independent measurements. Abbreviations: PD, polydopamine; PD NPs, polydopamine nanospheres; TCP, tissue culture plate.

Figure 7

Mechanical property and chemical component of composite fiber (A) ATR-IR. (B) Stress–strain curve. (C) Mechanical property. (D) Contact angle. Note: ^*P<0.05. Abbreviations: ATR, attenuated total reflection; BTZ, bortezomib; IR, infrared; PDO, polydioxanone; PD, polydopamine; UTS, ultimate tensile strength.

Figure 8

In vitro BTZ release profile from PDO composite fiber under acidic, basic, and NIR control conditions in PBS at 37°C. Notes: (A) Release profile under acidic (pH 5) and basic conditions (pH 7.4). (B) Under NIR irradiation (pH 7.4). The brown zone represents NIR “on” each at 60-second duration. Abbreviations: BTZ, bortezomib; NIR, near-infrared; PDO, polydioxanone.

Figure 9

Cell viability indices of combined therapy and the effect of treatment on cancer cells assessed by LIVE/DEAD^® assay with CT26 cancer cells. Notes: (A) Histogram showing CCK-8 data (OD) of CT26 cancer cell viability for control and therapy groups with no irradiation on 1, 3, and 5 days. (B) The viability of CT26 colon cancer cell co-incubated with PDO, PDO+PD, and PDO+PD-BTZ. (C and D) LIVE/DEAD^® cell microscopic images of PDO+PD nanofiber after 72 hours of treatment. (E and F) Combined photothermal and chemotherapy treatment using PDO+PD-BTZ nanofiber after 72 hours of treatment. One-way ANOVA post hoc Tukey test was used to indicate the significance (^*P<0.05, ^**P<0.01, and ^***P<0.001). Abbreviations: BTZ, bortezomib; PDO, polydioxanone; PD, polydopamine; TCP, tissue culture plate; OD, optical density; CCK-8, cell counting kit-8.