Cell-based high-throughput screening of cationic polymers for efficient DNA and siRNA delivery

Wu, Yihang; Zhou, Quanming; Li, Linxian; Chen, Guan-Yu; Ping, Yulei; Davidson, Gary; Levkin, Pavel A.; Gao, Liqian; Deng, Wenbin

doi:10.1016/j.actbio.2020.08.029

Cited by 11 publications

(5 citation statements)

References 38 publications

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“…HRMS were taken using MALDI-TOF. 1 H NMR spectra were recorded on 300, 400, and 500 MHz spectrometers in appropriate solvents and calibrated using residual undeuterated solvent as an internal reference, and the chemical shifts are shown in δ ppm scales.…”

Section: Methodsmentioning

confidence: 99%

“…This can be achieved through the targeted delivery of plasmids, silencing RNA, or the revolutionary CRISPR/Cas9 gene-editing system. While viral vectors have historically been the go-to choose for nucleic acid delivery [1][2][3][4][5][6][7] they are not without their limitations. These include the potential for severe immune responses and the risk of insertional mutagenesis, which can lead to the activation of oncogenes.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Amino Acid‐Based Cationic Lipids and Study of the Role of the Cationic Head Group for Enhanced Drug and Nucleic Acid Delivery

Mandal,

Mallik,

Bhoumick

et al. 2024

ChemBioChem

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Leveraging liposomes for drug and nucleic acid delivery, though promising due to reduced toxicity and ease of preparation, faces challenges in stability and efficiency. To address this, we synthesized cationic amphiphiles from amino acids (arginine, lysine, and histidine). Histidine emerged as the superior candidate, leading to the development of three histidine‐rich cationic amphiphiles for liposomes. Using the hydration method, we have prepared the liposomes and determined the optimal N/P ratios for lipoplex formation via gel electrophoresis. In vitro transfection assays compared the efficacy of our lipids to Fugene, while MTT assays gauged biocompatibility across cancer cell lines (MDA‐MB 231 and MCF‐7). The histidine‐based lipid demonstrated marked potential in enhancing drug and nucleic acid delivery. This improvement stemmed from increased zeta potential, enhancing electrostatic interactions with nucleic acids and cellular uptake. Our findings underscore histidine's crucial role over lysine and arginine for effective delivery, revealing a significant correlation between histidine abundance and optimal performance. This study paves the way for histidine‐enriched lipids as promising candidates for efficient drug and nucleic acid delivery, addressing key challenges in the field.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of Amino Acid‐Based Cationic Lipids and Study of the Role of the Cationic Head Group for Enhanced Drug and Nucleic Acid Delivery

Mandal,

Mallik,

Bhoumick

et al. 2024

ChemBioChem

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“…Similar to the mechanism of cationic liposomes, cationic polymers form nanosized complexes by binding to negatively charged nucleic acids through electrostatic adsorption, and timely escape from endosomes via the “proton sponge” effect, avoiding rapid degradation of nucleic acids. 55 , 56 As gene carriers, the advantages of cationic polymers include simple/controllable synthesis process, modifiable structure, flexible/diverse functions, low immunogenicity, and high transfection efficiency. Among them, polyethylenimine (PEI), poly (L-lysine) (PLL), and chitosan are the most representative cationic polymer carriers for gene therapy.…”

Section: Nanodelivery and Release Systemsmentioning

confidence: 99%

Stimulus-Responsive Nanodelivery and Release Systems for Cancer Gene Therapy: Efficacy Improvement Strategies

Zeng,

Zhang,

Liu

et al. 2024

IJN

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Introduction of exogenous genes into target cells to overcome various tumor diseases caused by genetic defects or abnormalities and gene therapy, a new treatment method, provides a promising strategy for tumor treatment. Over the past decade, gene therapy has made exciting progress; however, it still faces the challenge of low nucleic acid delivery and release efficiencies. The emergence of nonviral vectors, primarily nanodelivery and release systems (NDRS), has resulted in a historic breakthrough in the application of gene therapy. NDRS, especially stimulus-responsive NDRS that can respond in a timely manner to changes in the internal and external microenvironment (eg, low pH, high concentration of glutathione/reactive oxygen species, overexpressed enzymes, temperature, light, ultrasound, and magnetic field), has shown excellent loading and release advantages in the precision and efficiency of tumor gene therapy and has been widely applied. The only disadvantage is that poor transfection efficiency limits the in-depth application of gene therapy in clinical practice, owing to the presence of biological barriers in the body. Therefore, this review first introduces the development history of gene therapy, the current obstacles faced by gene delivery, strategies to overcome these obstacles, and conventional vectors, and then focuses on the latest research progress in various stimulus-responsive NDRS for improving gene delivery efficiency. Finally, the future challenges and prospects that stimulus-responsive NDRS may face in clinical application and transformation are discussed to provide references for enhancing in-depth research on tumor gene therapy.

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“…Cationic polymers (also known as polycations) are high‐molecular‐weight polymers with positive surface charges. In the past two decades, with the development of synthetic chemistry and biochemistry, various natural or synthetic cationic polymers have been reported as gene delivery systems (Blakney et al, 2020; Li et al, 2018; Wu et al, 2020).…”

Section: Nanocarrier‐mediated Delivery Of Sirnamentioning

confidence: 99%

Nanocarrier‐delivered small interfering RNA for chemoresistant ovarian cancer therapy

Zou

Liu³

et al. 2021

WIREs RNA

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Ovarian cancer is the fifth leading cause of cancer-related death in women in the United States. Because success in early screening is limited, and most patients with advanced disease develop resistance to multiple treatment modalities, the overall prognosis of ovarian cancer is poor. Despite the revolutionary role of surgery and chemotherapy in curing ovarian cancer, recurrence remains a major challenge in treatment. Thus, improving our understanding of the pathogenesis of ovarian cancer is essential for developing more effective treatments. In this review, we analyze the underlying molecular mechanisms leading to chemotherapy resistance. We discuss the clinical benefits and potential challenges of using nanocarrier-delivered small interfering RNA to treat chemotherapy-resistant ovarian cancer. We aim to elicit collaborative studies on nanocarrier-delivered small interfering RNA to improve the long-term survival rate and quality of life of patients with ovarian cancer. This article is categorized under: RNA Methods > RNA Nanotechnology Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action K E Y W O R D S chemotherapy resistance, nanocarrier, ovarian cancer, small interfering RNA, targeted therapy 1 | INTRODUCTION Ovarian cancer is the second most common gynecological cancer and the fifth leading cause of cancer-related death among women in the United States. Globally, approximately 313,959 newly diagnosed cases and 207,252 deaths were reported in 2020 (GLOBOCAN, 2020). Ovarian cancer usually occurs shortly before or after menopause, and the average age of diagnosis is around 63 years (Shen et al., 2017). Histologically, ovarian cancer is divided into three types: epithelial tumors (>85% of cases), stromal tumors, and germ cell tumors. Each subtype has distinct etiology and clinical characteristics. Most cases of ovarian cancer are diagnosed in an advanced stage (Stage III/IV), as patients often have no obvious symptoms or only mild and atypical symptoms during the early stage of disease (Goff et al., 2000;Natanzon et al., 2018;Smyth et al., 1997). Although diagnostic technology has advanced in the past decade, it is still difficult to detect early-stage ovarian cancer. Currently, surgery and chemotherapy are commonly used to treat ovarian cancer (Schorge et al., 2010). Particularly, platinum-and taxane-based chemotherapy after surgery is the standard regimen for patients with advanced disease (

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Cell-based high-throughput screening of cationic polymers for efficient DNA and siRNA delivery

Cited by 11 publications

References 38 publications

Synthesis of Amino Acid‐Based Cationic Lipids and Study of the Role of the Cationic Head Group for Enhanced Drug and Nucleic Acid Delivery

Synthesis of Amino Acid‐Based Cationic Lipids and Study of the Role of the Cationic Head Group for Enhanced Drug and Nucleic Acid Delivery

Stimulus-Responsive Nanodelivery and Release Systems for Cancer Gene Therapy: Efficacy Improvement Strategies

Nanocarrier‐delivered small interfering RNA for chemoresistant ovarian cancer therapy

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