Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer
机构:[1]Sun Yat Sen Mem Hosp, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China;[2]Sun Yat Sen Mem Hosp, Dept Emergency Med, Guangzhou, Guangdong, Peoples R China;[3]Sun Yat Sen Univ, Canc Ctr, Dept Thorac Surg, Guangzhou, Guangdong, Peoples R China;临床科室胸科中山大学肿瘤防治中心[4]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Radiol, 107 Yanjiang Xi Rd, Guangzhou 510120, Guangdong, Peoples R China;[5]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gastroenterol, 107 Yanjiang Xi Rd, Guangzhou 510120, Guangdong, Peoples R China
Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)-and disulfide (SS)-polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen: phosphate (N: P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N: P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N: P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a T-2-weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers.
基金:
We would like to thank Lu Zhang, PhD from the School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, China, for kindly providing technical support for chemical synthesis of the polymer nanocarrier.
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外文
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出版当年[2017]版:
大类|2 区工程技术
小类|2 区药学3 区纳米科技
最新[2023]版:
大类|2 区医学
小类|2 区药学3 区纳米科技
第一作者:
第一作者机构:[1]Sun Yat Sen Mem Hosp, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China;
通讯作者:
通讯机构:[1]Sun Yat Sen Mem Hosp, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China;[4]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Radiol, 107 Yanjiang Xi Rd, Guangzhou 510120, Guangdong, Peoples R China;[5]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gastroenterol, 107 Yanjiang Xi Rd, Guangzhou 510120, Guangdong, Peoples R China
推荐引用方式(GB/T 7714):
Luo Xin,Peng Xia,Hou Jingying,et al.Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer[J].INTERNATIONAL JOURNAL OF NANOMEDICINE.2017,12:5331-5343.doi:10.2147/IJN.S137245.
APA:
Luo, Xin,Peng, Xia,Hou, Jingying,Wu, Shuyun,Shen, Jun&Wang, Lingyun.(2017).Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer.INTERNATIONAL JOURNAL OF NANOMEDICINE,12,
MLA:
Luo, Xin,et al."Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer".INTERNATIONAL JOURNAL OF NANOMEDICINE 12.(2017):5331-5343