Reduction-responsive cross-linked stearyl peptide for effective delivery of plasmid DNA

Yan, Chong; Tai, Zongguang; Wang, Xiaoyu; Liu, Jiyong; Wu, Xin; Zhang, Lijuan; Zhang, Wei; Tian, Jing; Gao, Yuan; Gao, Shen

doi:10.2147/ijn.s82413

Cited by 10 publications

(2 citation statements)

References 32 publications

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“…Cancer cells exhibit significantly elevated levels of GSH, several times higher than normal cells, along with increased expression of the enzyme. 56 Given that lignins are very responsive to GSH, their depletion of GSH in cancer cells disrupts the balance between GSH and ROS, leading to increased ROS levels. This elevation precipitates oxidative damage to cellular components, including lipids, proteins, and DNA, consequently expediting cell death.…”

Section: Resultsmentioning

confidence: 99%

“…The delicate balance between GSH and the ROS is vital for protecting cells from oxidative stress. Cancer cells exhibit significantly elevated levels of GSH, several times higher than normal cells, along with increased expression of the enzyme . Given that lignins are very responsive to GSH, their depletion of GSH in cancer cells disrupts the balance between GSH and ROS, leading to increased ROS levels.…”

Section: Resultsmentioning

confidence: 99%

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Antitumor Effects of Carrier-Free Functionalized Lignin Materials on Human Hepatocellular Carcinoma (HepG2) Cells

Wang,

Lu,

Liu

et al. 2024

ACS Nano

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Lignin, as an abundant aromatic biopolymer in plants, has great potential for medical applications due to its active sites, antioxidant activity, low biotoxicity, and good biocompatibility. In this work, a simple and ecofriendly approach for lignin fractionation and modification was developed to improve the antitumor activity of lignin. The lignin fraction KL-3 obtained by the lignin gradient acid precipitation at pH = 9−13 showed good cytotoxicity. Furthermore, the cell-feeding lignin after additional structural modifications such as demethylation (DKL-3), sulfonation (SL-3), and demethylsulfonation (DSKL-3) could exhibit higher glutathione responsiveness in the tumor microenvironment, resulting in reactive oxygen species accumulation and mitochondrial damage and eventually leading to apoptosis in HepG2 cells with minimal damage to normal cells. The IC 50 values for KL-3, SL-3, and DSKL-3 were 0.71, 0.57, and 0.41 mg/mL, respectively, which were superior to those of other biomass extractives or unmodified lignin. Importantly, in vivo experiments conducted in nude mouse models demonstrated good biosafety and effective tumor destruction. This work provides a promising example of constructing carrier-free functionalized lignin antitumor materials with different structures for inhibiting the growth of human hepatocellular carcinoma (HepG2) cells, which is expected to improve cancer therapy outcomes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Antitumor Effects of Carrier-Free Functionalized Lignin Materials on Human Hepatocellular Carcinoma (HepG2) Cells

Wang,

Lu,

Liu

et al. 2024

ACS Nano

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Histidine‐enhanced gene delivery systems: The state of the art

Hooshmand

Sabet

Hasanzadeh

et al. 2022

The Journal of Gene Medicine

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Gene therapy has emerged as a promising tool for treating different intractable diseases, particularly cancer or even viral diseases such as COVID-19 (coronavirus disease 2019). In this context, various non-viral gene carriers are being explored to transfer DNA or RNA sequences into target cells. Here, we review the applications of the naturally occurring amino acid histidine in the delivery of nucleic acids into cells.The biocompatibility of histidine-enhanced gene delivery systems has encouraged their wider use in gene therapy. Histidine-based gene carriers can involve the modification of peptides, dendrimers, lipids or nanocomposites. Several linear polymers, such as polyethylenimine, poly-L-lysine (synthetic) or dextran and chitosan (natural), have been conjugated with histidine residues to form complexes with nucleic acids for intracellular delivery. The challenges, opportunities and future research trends of histidine-based gene deliveries are investigated.

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Dual-targeting and microenvironment-responsive micelles as a gene delivery system to improve the sensitivity of glioma to radiotherapy

Jiao

Meng

et al. 2019

Acta Pharmaceutica Sinica B

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Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood—brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K n (s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K n (s-s)R8-An micelles maintained a reasonable size (80–160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency in vitro , improved uptake in glioma cells and good biocompatibility in vitro and in vivo . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells in vitro . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.

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Reduction-responsive cross-linked stearyl peptide for effective delivery of plasmid DNA

Cited by 10 publications

References 32 publications

Antitumor Effects of Carrier-Free Functionalized Lignin Materials on Human Hepatocellular Carcinoma (HepG2) Cells

Antitumor Effects of Carrier-Free Functionalized Lignin Materials on Human Hepatocellular Carcinoma (HepG2) Cells

Histidine‐enhanced gene delivery systems: The state of the art

Dual-targeting and microenvironment-responsive micelles as a gene delivery system to improve the sensitivity of glioma to radiotherapy

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