Zn-Dipicolylamine-Based ROS-Responsive Bola-Lipid Nanoparticles for Efficient Protein Delivery and Tumor Immunotherapy

Zhao, Rui-Mo; Hu, Yue; Chen, Ping; Hei, Meng-Wei; Yu, Xiao-Qi; Zhang, Ji

doi:10.1021/acsanm.3c04192

Cited by 1 publication

(4 citation statements)

References 56 publications

(82 reference statements)

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“…ROS-induced n-TDZn decomposition has been demonstrated by 1 H NMR, HR-MS, and Ellman’s test in the previous report . Herein, the ROS responsiveness of n-TDZn lipoplexes in terms of DNA release was evaluated by a gel retardation experiment.…”

Section: Experimental Sectionmentioning

confidence: 75%

“…The thioacetal-contained bola-type lipids have been found to have ROS-responsive ability in previous studies . Herein, we further evaluated the ROS-triggered degradation of LNPs in terms of DNA release by a gel electrophoresis assay.…”

Section: Resultsmentioning

confidence: 99%

“…The target lipids, n-TDZn, and relevant LNPs were prepared according to a previous study . To prepare the n-TDZn LNPs/DNA complexes (lipoplexes), various amounts of n-TDZn LNPs were mixed with a constant amount of DNA at various charge ratios (±).…”

Section: Experimental Sectionmentioning

confidence: 99%

“…It was found that cationic lipids with zinc-coordinated 2,2′-dipicolylamine (Zn-DPA) as a cationic headgroup exhibited high gene transfection efficiency, , while our previous study also demonstrated that symmetrical bola-lipids with Zn-DPA could be used as antigen–protein delivery vectors . In this study, we further expanded the application of the bola-lipids and studied the gene transfection and gene/PDT combined therapy effects of such materials (Figure ).…”

Section: Introductionmentioning

confidence: 97%

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ROS-Responsive Bola-Lipid Nanoparticles as a Codelivery System for Gene/Photodynamic Combination Therapy

Zhao,

Zhang,

Tian

et al. 2024

Mol. Pharmaceutics

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The nonviral delivery systems that combine genes with photosensitizers for multimodal tumor gene/photodynamic therapy (PDT) have attracted much attention. In this study, a series of ROS-sensitive cationic bola-lipids were applied for the gene/ photosensitizer codelivery. Zn-DPA was introduced as a cationic headgroup to enhance DNA binding, while the hydrophobic linking chains may facilitate the formation of lipid nanoparticles (LNP) and the encapsulation of photosensitizer Ce6. The length of the hydrophobic chain played an important role in the gene transfection process, and 14-TDZn containing the longest chains showed better DNA condensation, gene transfection, and cellular uptake. 14-TDZn LNPs could well load photosensitizer Ce6 to form 14-TDC without a loss of gene delivery efficiency. 14-TDC was used for codelivery of p53 and Ce6 to achieve enhanced therapeutic effects on the tumor cell proliferation inhibition and apoptosis. Results showed that the codelivery system was more effective in the inhibition of tumor cell proliferation than individual p53 or Ce6 monotherapy. Mechanism studies showed that the production of ROS after Ce6 irradiation could increase the accumulation of p53 protein in tumor cells, thereby promoting caspase-3 activation and inducing apoptosis, indicating some synergistic effect. These results demonstrated that 14-TDC may serve as a promising nanocarrier for gene/PDT combination therapy.

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Section: Experimental Sectionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Experimental Sectionmentioning

confidence: 99%