Active targeted drug delivery system constructed from functionalized pillararenes for chemo/photodynamic synergistic therapy

doi:10.1007/s11705-024-2489-y

2024, Vol. 18

Issue (11) : 138 https://doi.org/10.1007/s11705-024-2489-y

Active targeted drug delivery system constructed from functionalized pillararenes for chemo/photodynamic synergistic therapy

Bing Lu(

), Yuying Huang, Jiachen Xia, Yong Yao(

)

College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China

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Abstract

Nowadays, although functionalized pillararenes have been widely designed to be used in drug delivery system, targeted group modified pillararenes have been seldom reported and used in tumor multimodal therapy. Herein, a functionalized pillararene with a polyethylene glycol chain and triphenylphosphonium cation WP5-PEG-TPP was designed and synthesized. Subsequently, an active targeted drug delivery system was constructed based on its host-guest interactions with a newly designed porphyrin derivative, Py-Por. The experimental results demonstrated that this drug delivery system has exhibited excellent targeting ability against tumor cells, but interestingly it could not enter normal cells. After loading the hypoxia-activated prodrug tirapazamine, the prepared nanodrugs displayed high lethality to tumor cells due to their chemo/photodynamic synergistic therapy capability, but negligible toxicity to normal cells. Preliminary therapeutic mechanism study elucidated the synergistic therapy process.

Keywords durg delivery system active targeting pillararene chemo/photodynamic synergistic therapy.

Corresponding Author(s): Bing Lu,Yong Yao

Just Accepted Date: 11 June 2024 Issue Date: 31 July 2024

Cite this article:

Bing Lu,Yuying Huang,Jiachen Xia, et al. Active targeted drug delivery system constructed from functionalized pillararenes for chemo/photodynamic synergistic therapy[J]. Front. Chem. Sci. Eng., 2024, 18(11): 138.

URL:

https://academic.hep.com.cn/fcse/EN/10.1007/s11705-024-2489-y
https://academic.hep.com.cn/fcse/EN/Y2024/V18/I11/138

Fig.1 The chemical structures of WP5-PEG-TPP and Py-Por, and their applications in mitochondria-targeting chemo/photodynamic synergistic therapy.

Fig.2 The ¹H NMR spectra of (a) G_M (10 μmol·L^?1), (b) G_M + WP5-PEG-TPP (10 μmol·L^?1 + 10 μmol·L^?1) and (c) WP5-PEG-TPP (10 μmol·L^?1) in CDCl₃.

Fig.3 (a) DLS data of the unloaded NPs; (b) DLS data of the TPZ-loaded NPs. Inserted graphs: TEM images of corresponding NPs. Scale bar: 200 nm.

Fig.4 (a) Staining images of HeLa cells by MitoTracker green, TPZ-loading NPs and Hoechst 33342; (b) ROS detection in HeLa cells received different treatments. Scale bar: 50 μm.

Fig.5 The cell viability data, and calcein AM/propidium iodide staining images of (a) HeLa, (b) 4T1 and (c) HL-7702 cells after received different treatments (Scale bar: 50 μm).

Fig.6 JC-1 staining images of MMP in HeLa cells after received different treatments (Scale bar: 50 μm).

Fig.7 (a) The cell viability data of unloaded NPs + laser treated HeLa cells under normoxic and hypoxic conditions, respectively; (b) the cell viability data of TPZ-loading NPs + laser treated HeLa cells under normoxic and hypoxic conditions, respectively.

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[1]	Bing Lu, Zhecheng Zhang, Meiyu Qi, Yuehua Zhang, Hualing Yang, Jin Wang, Yue Ding, Yang Wang, Yong Yao. All-in-one functional supramolecular nanoparticles based on pillar[5]arene for controlled generation, storage and release of singlet oxygen[J]. Front. Chem. Sci. Eng., 2023, 17(3): 307-313.

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