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. 2021 Jul 20:16:4901-4911.
doi: 10.2147/IJN.S319089. eCollection 2021.

An Acceptor-π-Donor Structured Organic Chromophore for NIR Triggered Thermal Ablation of Tumor via DNA Damage-Mediated Apoptosis

Di Zhang  1 , Jinghong Yang  2 , Chuang Liu  1 , Sheng Ye  1 , Qianbing Zhang  2 , Ruiyuan Liu  1
Affiliations

An Acceptor-π-Donor Structured Organic Chromophore for NIR Triggered Thermal Ablation of Tumor via DNA Damage-Mediated Apoptosis

Di Zhang et al. Int J Nanomedicine. .

Abstract

Introduction: It will be challenging to develop high-performance organic chromophores for light-triggered thermal ablation of the tumor. Besides, the mechanisms of organic chromophores for tumor therapy remain unclear. Herein, an acceptor-π-donor (A-π-D) structured organic chromophore based on 2-dicyanomethylenethiazole named PTM was developed for photothermal therapy (PTT) of tumors.

Methods and results: Biocompatible PTM nanoparticles (PTM NPs) were fabricated by enclosing PTM with Pluronic F-127. The results of optical and photothermal properties of PTM NPs showed robust near-infrared (NIR) absorption, excellent photostability and high photothermal conversion efficiency (56.9%). The results of flow cytometry, fluorescence microscopy, apoptosis, CCK-8 assays and animal experiments showed that PTM NPs had a good killing effect on tumors under NIR laser irradiation. Furthermore, mechanistic studies, RNA-seq and biological analysis revealed that PTM NPs can cause tumor cell death via DNA damage-mediated apoptosis.

Conclusion: Light-induced thermal ablation effects of PTM NPs in vitro and vivo were surveyed. Collectively, our studies provided a new approach to developing a safe and effective photothermal agent for cancer treatment.

Keywords: 2-dicyanomethylenethiazole; DNA damage induced apoptosis; NIR absorbing chromophore; RNA-seq; biological analysis; photothermal therapy.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
(A) The absorption spectrum of PTM NPs (200 μg/mL) in Water. (B) DLS of PTM NPs (10 μg/mL) insert SEM and TEM of PTM NPs. (C) Photothermal heating curves of PTM NPs (80 μg/mL) irradiated for 10 min using a 808 nm laser at varied power densities (0, 0.5, 1.0, 1.5, and 2.0 W/cm2). (D) The temperature evolution of PTM NPs with different concentrations under 808 nm laser irradiation (1.5 W/cm2, 10 min). (E) Temperature elevation of PTM NPs (120 μg/mL) under five on/off cycles (1.0 W/cm2). (F) Corresponding near infrared photographs of PTM NPs (80 μg/mL) under NIR laser irradiation (808nm, 1.5 W/cm2, 5 min). (G) HOMO and LUMO calculated by DFT at the B3LYP/6-31G (d,p) basis set.
Figure 2
Figure 2
(A) AM/PI fluorescence imaging of 4T1cells with PTM NPs (200 μg/mL) in the absence or presence of NIR laser irradiation (808nm, 1.5 W/cm2, 10 min). The scale is 100μm. (B) Representative FCM profiles of 4T1cells with PTM NPs (80 μg/mL) in the absence or presence of NIR laser irradiation (808 nm, 1.5 W/cm2, 5 min). (C) PTT induced the Bcl-2, BAX, H2AX, and γH2AX expression in 4T1 cells after different treatments.
Figure 3
Figure 3
(A) and (B) Tumor temperature of PTM + NIR laser irradiation group before and after irradiation (808nm, 1.0 W/cm2, 1 min). (C) Tumor growth curves of mice after different treatments. Results are expressed as mean ± S.E. * P < 0.05 compared with the PTM+NIR laser irradiation group. (D) Photographs of the dissected tumors after different treatment, (E) Dissected tumors weight after different treatment. Results are expressed as mean ± S.E. * P < 0.05 compared with the PTM+NIR laser irradiation group. (F) Body weight curve of mice after PTM+NIR laser irradiation group. (G) TUNEL assay of the tumor tissues after PTT.
Figure 4
Figure 4
(A) Heatmap showed the differential expressed genes after PTM NPs treated. (B) Enriched KEGG pathway analysis of differentially expressed genes after PTM NPs treated. (C) and (D) Enriched GO biological process of up-regulated genes (orange) and down-regulated genes (blue) in PTM NPs treated group. The X-axis of the histogram is -log10 (P-value) of individual terms calculated by right-sided hypergeometric test and corrected with Bonferroni. GO categories are indicated on Y-axis.
Figure 5
Figure 5
(A) H&E staining images of major organs in the mice after the intravenous injection. (B) The influence of PTM NPs on the hematopoietic system of mice.
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