Photoacoustic/Near-infrared Ⅱ Fluorescence Dual-mode Imaging and Photo/Chemodynamic Synergistic Therapy Effects of DPP-PEG/BSA-MnO2

doi:10.6023/A25050141

Acta Chimica Sinica ›› 2025, Vol. 83 ›› Issue (11): 1324-1334.DOI: 10.6023/A25050141 Previous Articles Next Articles

Article

DPP-PEG/BSA-MnO₂的光声/近红外二区荧光双模成像及光疗/化学动力学治疗协同效应研究

李佳启^a, 黄艳琴^a^,^*(), 丁桂策^a, 张瑞^b^,^*(), 刘兴奋^a, 范曲立^a, 黄维^a^,^c^,^*()

^a 南京邮电大学信息材料与纳米技术研究院柔性电子全国重点实验室南京 210023
^b 东南大学附属中大医院眼科南京 210009
^c 西北工业大学柔性电子前沿科学中心工信部柔性电子重点实验室西安 710072

投稿日期:2025-05-05 发布日期:2025-07-04
通讯作者: 黄艳琴, 张瑞, 黄维
基金资助:
江苏省基础研究计划(BK20243057); 江苏高校优势学科建设工程(YX03001); 以及东南大学附属中大医院江苏省高水平医院建设经费(YKK24271)

Photoacoustic/Near-infrared Ⅱ Fluorescence Dual-mode Imaging and Photo/Chemodynamic Synergistic Therapy Effects of DPP-PEG/BSA-MnO₂

Li Jiaqi^a, Huang Yanqin^a^,^*(), Ding Guice^a, Zhang Rui^b^,^*(), Liu Xingfen^a, Fan Quli^a, Huang Wei^a^,^c^,^*()

^a State Key Laboratory of Flexible Electronics (LoFE), Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China
^b Department of Ophthalmology, Zhongda Hospital, Southeast University, Nanjing 210009, China
^c Frontiers Science Center for Flexible Electronics (FSCFE), MIIT Key Laboratory of Flexible Electronics (KLoFE), Northwestern Polytechnical University, Xi'an 710072, China

Received:2025-05-05 Published:2025-07-04
Contact: Huang Yanqin, Zhang Rui, Huang Wei
Supported by:
Basic Research Program of Jiangsu(BK20243057); Priority Academic Program Development of Jiangsu Higher Education Institutions(YX03001); Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds(YKK24271)

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Abstract

In this paper, a multifunctional nanotheranostic agent DPP-PEG/BSA-MnO₂ was constructed for photoacoustic (PA)/near-infrared fluorescence (NIR Ⅱ FL) dual-mode imaging and photodynamic (PDT)/photothermal (PTT)/chemodynamic (CDT) synergistic therapy effects. A diketopyrrolopyrrole (DPP)-based amphiphilic conjugated polymer, DPP-PEG, was synthesized by direct (hetero) arylation polymerization (DHAP) of a DPP derivative monomer modified with polyethylene glycol (PEG) hydrophilic side chains and another DPP derivative monomer substituted with 2-ethylhexyl side chains. DPP-PEG nanoparticles (NPs) exhibited strong fluorescence emission in the NIR II region of 1000~1400 nm with a fluorescence quantum yield of 0.374%, which can quickly light up the mouse's systemic vascular network within 2 min, achieving clear fluorescence imaging of brain and leg blood vessels. DPP-PEG was complexed with bovine serum albumin (BSA)-manganese dioxide (MnO₂) to construct a water-soluble composite nanomaterial DPP-PEG/BSA-MnO₂ (abbreviated as DPP-PEG/B-M). Comparative studies with DPP-PEG/B and B-M showed that DPP-PEG/B-M exhibited evident PDT/PTT/CDT synergistic effect in the tumor microenvironment (TME). Both DPP-PEG/B and DPP-PEG/B-M can effect-tively inhibit the proliferation effect in the tumor microenvironment (TME). Both DPP-PEG/B and DPP-PEG/B-M can effectively inhibit the proliferation of 4T1 tumor cells under 808 nm laser irradiation, as DPP-PEG produced excellent PDT/PTT synergistic effects. Compared with DPP-PEG/B, DPP-PEG/B-M showed a significant increase in cytotoxicity under the same conditions. The overexpressed glutathione (GSH) and H₂O₂ in TME can effectively convert MnO₂ into Mn^2＋, which further underwent a Fenton-like reaction with H₂O₂ to generate •OH, thereby producing additional CDT therapeutic effects. Furthermore, MnO₂ reacted with H₂O₂ to produce O₂, promoting the generation of ¹O₂ and enhancing the PDT effect. The consumption of MnO₂ weakened the scavenging effect of GSH on •OH and ¹O₂, further synergistically enhancing the PDT/CDT effect. Moreover, DPP-PEG/B-M was injected into 4T1 tumor-bearing mice via the tail vein. 24 h post-injection, the photoacoustic and NIR-II fluorescence signals at the tumor site reached their highest intensity, indicating that DPP-PEG/B-M can be enriched to the tumor site through the enhanced permeation and retention (EPR) effect. Therefore, DPP-PEG/B-M exhibited excellent tumor-targeting photoacoustic imaging and NIR-II fluorescence imaging performance in 4T1 tumor-bearing mice, and was expected to be applied in PDT/PTT/CDT synergistic therapy guided by photoacoustic/NIR-II fluorescence dual-mode imaging, playing a role in precise and efficient tumor therapy.

Key words: conjugated polymers, manganese dioxide, dual-mode imaging, photodynamic therapy, photothermal therapy, chemodynamic therapy, synergistic therapy

Cite this article

Li Jiaqi, Huang Yanqin, Ding Guice, Zhang Rui, Liu Xingfen, Fan Quli, Huang Wei. Photoacoustic/Near-infrared Ⅱ Fluorescence Dual-mode Imaging and Photo/Chemodynamic Synergistic Therapy Effects of DPP-PEG/BSA-MnO₂[J]. Acta Chimica Sinica, 2025, 83(11): 1324-1334.

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Fig. & Tab. 6

Figure 1. Schematic illustration of preparation and applications of DPP-PEG/B-M in tumor diagnosis and therapy

Figure 2. (a) UV-Vis-NIR absorption and fluorescence (λexc: 808 nm) spectra of DPP-PEG aqueous solution (inset: photograph of DPP-PEG aqueous solution); hydrodynamic sizes and TEM images of (b) B-M, (c) DPP-PEG/B-M, and (d) DPP-PEG/B; (e) comparison of hydrodynamic sizes of B-M, DPP-PEG/B, and DPP-PEG/B-M; (f) Zeta potentials of B-M, DPP-PEG/B, and DPP-PEG/B-M

Figure 3. (a) Energy-dispersive X-ray spectroscopy spectrum of DPP-PEG/B-M; (b) photos of DPP-PEG/B, B-M, and DPP-PEG/B-M solid state; (c) DPP-PEG/B, B-M, and DPP-PEG/B-M in the solution of neutral PBS (pH 7.4) and weakly acidic PBS (pH 5.5, 100 μmol/L H2O2); (d) time-dependent dissolved oxygen concentration of DPP-PEG/B, B-M, and DPP-PEG/B-M in acidic PBS (pH 5.5, 100 μmol/L H2O2); (e) UV-Vis-NIR absorption spectra and (f) fluorescence spectra (λexc: 808 nm) of DPP-PEG/B, B-M, and DPP-PEG/B-M in neutral PBS (pH 7.4) and acidic PBS (pH 5.5, 100 μmol/L H2O2)

Figure 4. (a) Linear relationship between absorbance changes of DPBF and irradiation time (808 nm, 1 W/cm²) in neutral PBS (pH 7.4) or weakly acidic PBS (pH 5.5, 100 μmol/L H₂O₂) containing DPP-PEG/B-M or DPP-PEG/B; (b) intracellular detection of ¹O₂ in 4T1 cells incubated with DPP-PEG/B-M and DPP-PEG/B using DCFH-DA as a fluorescent probe; (c) absorption spectral changes of MB in NaHCO₃ buffer (25 mmol/L) after mixing DPP-PEG/B-M, GSH, H₂O₂, and MB for different durations; (d) absorption spectra of MB at varying GSH concentrations (0~50 mmol/L) after mixing DPP-PEG/B-M, GSH, H₂O₂, and MB for 0.5 h; (e) temperature elevation curves of DPP-PEG/B-M (400 μg/mL) under 808 nm laser irradiation at different power densities; (f) photothermal response of DPP-PEG/B-M during five on/off cycles under 808 nm laser irradiation (1.2 W/cm²); (g) single photothermal cycle from (f); (h) linear relationship between time and −lnθ derived from the cooling phase in (g)

Figure 5. Cell viability of 3T3 and 4T1 cells coincubated with (a) DPP-PEG/B or (b) DPP-PEG/B-M under dark conditions; (c) cell viability of 4T1 cells after PDT, PTT and PDT/PTT treatment with DPP-PEG/B, and cell viability of 4T1 cells after PTT/PDT treatment with DPP-PEG/B-M (808 nm laser irradiation, 8 min, 0.8 W/cm²); (d) AM/PI staining of 4T1 cells coincubated with DPP-PEG/B-M: (1) under dark condition and (2) under laser irradiation (808 nm, 0.8 W/cm², 8 min); AM/PI staining of 4T1 cells coincubated with DPP-PEG/B: (3) under dark condition and (4) under laser irradiation (808 nm, 0.8 W/cm², 8 min)

Figure 6. (a) NIR-II fluorescence imaging of systemic vasculature in mice at various time points post intravenous injection of DPP-PEG NPs in PBS; (b) linear relationship between the concentration of DPP-PEG/B-M in PBS and NIR-II fluorescence intensity; (c) linear relationship between the concentration of DPP-PEG/B-M in PBS and photoacoustic intensity; (d) in vivo NIR-II fluorescence imaging and (e) in vivo photoacoustic imaging of 4T1 tumor-bearing mice at different time points after intravenous injection of DPP-PEG/B-M in PBS (λexc: 808 nm; red circles indicate tumor regions)

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DPP-PEG/BSA-MnO₂的光声/近红外二区荧光双模成像及光疗/化学动力学治疗协同效应研究

Photoacoustic/Near-infrared Ⅱ Fluorescence Dual-mode Imaging and Photo/Chemodynamic Synergistic Therapy Effects of DPP-PEG/BSA-MnO₂

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