Design and Synthesis of Nanoscale Zr-Porphyrin IX Framework for Synergistic Photodynamic and Sonodynamic Therapy of Tumors

doi:10.6023/A24010035

Abstract

Multifunctional nanomaterials with photodynamic and sonodynamic properties have attracted wide attention in tumor therapy, but the design and preparation of “all-in-one” type of multifunctional nanomaterials with single component remains challenging. Herein the “all-in-one” type of Zr-PpIX (protoporphyrin IX) coordination nanoparticles (ZrPs) with photodynamic and sonodynamic properties was reported as efficient nano-photo/sonosensitizers. The ZrPs had an average size of about 50 nm. The survey X-ray photoelectron spectroscopy (XPS) spectrum showed strong Zr, C, N and O elemental signals, verifying that the ZrPs were composed of Zr/C/N/O elements. In addition, Fourier transform infrared (FTIR) spectra, ultraviolet-visible (UV-Vis) spectra and fluorescence (FL) spectra showed that the Zr⁴⁺ ion was only coordinated with the carboxyl group of PpIX. The ZrPs contained photo/sono-sensitizers PpIX, which could be excited by light/ultrasonic (US) to transform O₂ into cytotoxic ¹O₂. Furthermore, the ¹O₂ can be detected by using 1,3-diphenylisobenzofuran (DPBF) assay. When the mixed solution (ZrPs+DPBF) was excited by light, the peak of DPBF decreased rapidly as the light irradiation time increased, which suggested the generation of ¹O₂ by ZrPs+light. Similarly, the absorbance of DPBF+ZrPs was reduced as the US time increased, which confirmed the sonodynamic effect of ZrPs+US. After 5 min of light/US irradiation, 59.7% (light) and 22.8% (US) of DPBF was found to be oxidized by ZrPs, which showed effective ROS generation for photodynamic/sonodynamic therapy. Besides, ZrPs had shown good biosafety in vitro cellular experiments. ZrPs can be effectively endocytosed/uptaken by tumor cells. Meanwhile, ZrPs within cells can generate ROS upon light/US, affording photodynamic and/or sonodynamic effects. After 5 min of ZrPs with light/US irradiation, the cell viability goes down rapidly from about 100% to 5.3%. Therefore, the present study not only represents ZrPs as an “all-in-one” type of multifunctional nanomaterials for PDT-SDT therapy, but also provides some insights for designing other PpIX-related molecules with the similar structure for bioapplication.

Key words: all-in-one, protoporphyrin IX, photodynamic therapy, sonodynamic therapy

Cite this article

Yan Li, Wei Wang, Yuting Zhang, Shuzhang Xiao, Haichuang Lan, Peng Geng. Design and Synthesis of Nanoscale Zr-Porphyrin IX Framework for Synergistic Photodynamic and Sonodynamic Therapy of Tumors[J]. Acta Chimica Sinica, 2024, 82(4): 443-448.

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Fig. & Tab. 5

Figure 1. Synthesis diagram (A), SEM image (B), XPS survey spectrum (C) and Zr 3d spectrum (D) of ZrPs

Figure 2. FTIR spectra (A), UV-Vis spectra (B), and FL spectra (C) of ZrPs

Figure 3. (A) The scheme showing light/US-excited 1O2 generation from ZrPs. Time-dependent absorption-spectra of DPBF solution during the reaction ZrPs upon light (B) or US (C). (D) The oxidation performance of DPBF at different conditions (A0: initial absorbance; At: absorbance at time t)

Figure 4. Cytotoxicity of CT26 cell treated with the ZrPs for 24 h (A) and 48 h (B) (n=3)

Figure 5. Relative viability of PDT (A), SDT (B) and PDT-SDT (C) for different times (n=3)

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