Biofunctional core-shell polypyrrole-polyethylenimine nanocomplex for a locally sustained photothermal with reactive oxygen species enhanced therapeutic effect against lung cancer

Abstract

Background: Polymeric delivery systems have been elucidated over the last few years as an approach of achieving high therapeutic effect to the local site of malignant disease patients who have cancer. Polypyrrole (Ppy) is a potential organic conducting polymer which has long been recognized as a versatile material due to its excellent stability, conductive properties, and great absorbance in the range of near-infrared (NIR). It is tremendously versatile for use in various biomedical fields such as cancer therapy. NIR irradiation-activated treatment platform technologies are now being considered to be novel and exciting options in potential nanomedicine. However, the realistic photothermal use of Ppy-applied nanomaterials is yet in its early phase, and there are a few disadvantages of Ppy, such as its water insolubility. In the clinic, the common approach for treatment of lung cancer is the delivery of therapeutic active substances through intratumoral administration. Nevertheless, the tumor uptake, regional retention, mechanism of treatment, and tissue organ penetration regarding the developed strategy of this nanomaterial with photothermal hyperthermia are important issues for exerting effective cancer therapy.

Materials and methods: In this study, we developed a cationic Ppy-polyethylenimine nanocomplex (NC) with photothermal hyperthermia to study its physicochemical characteristics, including size distribution, zeta potential, and transmission electron microscopy, scanning electron microscopy, and Fourier transform infrared morphology. We also examined the cellular uptake effect on lung cancer cells, the photothermal properties, intracellularly generated reactive oxygen species (ROS), and cytotoxicity.

Results: The results suggested that this nanocarrier system was able to effectively attach onto lung cancer cells for subsequent endocytosis. The NCs taken up were able to absorb NIR and then converted the NIR light into local hyperthermia with its intracellular photothermal performance to provide local hyperthermic treatment. This regionally generated hyperthermia also induced ROS formation and improved the killing of lung cancer cells as a promising local photothermal therapy.

Conclusion: This development of a nanocarrier would bring a novel therapeutic strategy for lung cancer in the future.

Keywords: lung cancer therapy; nanomaterial; near-infrared; photothermal; polypyrrole.

Figure 1

(A) Results indicating photographic images of polypyrrole (Ppy) and Ppy–PEI NCs and their microscopic TEM. (B) Results of SEM showing prepared Ppy–PEI NCs with nano-size. DLS study shows the size distribution (C), zeta potential (D), and polydispersity index (E) of the different pH environments. Abbreviations: NC, nanocomplex; PEI, polyethylenimine; SEM, scanning electron microscopy; TEM, transmission electron microscopy; DLS, dynamic light scattering.

Figure 2

Photothermal property results. Temperature profile (A) at different concentrations of prepared NC and (B) at different pH environments. (C) Photothermal images (temperature value recorded by Thermocouple). The temperature elevated to 25 degree celsius is considered time 0 second. Abbreviations: DI, deionized; NC, nanocomplex.

Figure 3

(A) Fluorescence results show binding affinity of prepared NC in differently charged hydrogels and (B) their thermal properties. (C) Chemical structural change studied by Fourier transform infrared spectroscopy. Note: *Statistically significant, P < 0.05. Abbreviations: Cy, cyanine; NC, nanocomplex; NIR, near-infrared; PEI, polyethylenimine.

Figure 4

(A) Fluorescent images show cell interaction with different formulations. (B) Fluorescence intensity was calculated by ImageJ software, and the statistical data analysis compared with NC/NIR (cy5-). NC Fluorescence group, left: NC, right: NC/NIR). Notes: Black bar is ROS studied group; red bar is H2O2 studied group. *Statistically significant, P < 0.05. Abbreviations: H₂O₂, hydrogen peroxide; NC, nanocomplex; NIR, near-infrared; ns, nonsignificant; ROS, reactive oxygen species; DAPI, 4′,6-diamidino-2-phenylindole.

Figure 5

(A) Quantitative results of MTT cell viability with different treatments, comparison of control and PEI-Ppy. (B) The group of Ppy–PEI NCs attached onto cell membranes morphologically imaged by SEM. (C) The cell viability was qualitatively tested with a Live/Dead method. Note: *Statistically significant, P < 0.05. Abbreviations: NC, nanocomplex; NIR, near-infrared; PEI, polyethylenimine; Ppy, polypyrrole; SEM, scanning electron microscopy.

Figure 6

Schematic illustration showing the developed Ppy–PEI NCs bioapplied for lung cancer treatment. Abbreviations: ECM, extracellular matrix; NC, nanocomplex; NIR, near-infrared; PEI, polyethylenimine; Ppy, polypyrrole; ROS, reactive oxygen species.