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Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 170-187页

作者： Bao Li Haoran Niu Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma Xiaohong Liu Keda Zhang Huichao Xie Pingtian Ding School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical University Shenyang 110016 China Department of Basic Pharmaceutical Sciences School of Pharmacy Husson University Bangor ME 04401USA College of Pharmacy Shenzhen Technology UniversityShenzhen 518118China

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-sirna/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of vegf, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

关键词： Anti-angiogenesis Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)

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Dual-targeted lung cancer therapy via inhalation delivery of UCNP-sirna-AS1411 nanocages

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Cancer Biology & Medicine 2022年第7期19卷 1047-1060页

作者： Yu Han Yuming Yang Qiuyang Sun Bin Li Caixia Yue Yanlei Liu Jesús M.de la Fuente Daxiang Cui Institute of Nano Biomedicine and Engineering Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of EducationShanghai Engineering Research Center for Intelligent Diagnosis and Treatment InstrumentDepartment of Instrument Science&EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China National Engineering Center for Nanotechnology Collaborative Innovational Center for System BiologyShanghai 200241China Department of Neurosurgery Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 200092China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China Instituto de Nanociencia de Aragon(INA) Universidad de ZaragozaZaragoza 50018Spain

Objective:Although great progress has been made in the field of sirna gene therapy,safe,efficient,and targeted delivery of sirna are still major challenges in sirna therapeutics.Methods:We developed an up-conversion nanoparticle-based nanocage system.This system protected the sirna from being degraded by nucleases in organisms and selectively delivered the sirnas to the tumor sites,due to modifications of targeted molecules on the surfaces of nanocages and local inhalation.Results:The sirnas delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites,where they accumulated.Compared with the passive target and control groups,the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment.Conclusions:The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor sirnas to tumor sites.Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes,high tumor inhibition ratios,and longer survival times.

关键词： Nanomaterials VEGF siRNA lung cancer gene therapy sirna delivery

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