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Tetrahedral framework nucleic acids-based delivery of microRNA-155 inhibits choroidal neovascularization by regulating the polarization of macrophages

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Bioactive Materials 2022年第8期7卷 134-144页

作者： Xin Qin Lirong Xiao Ni Li Chen Hou Wenman Li Jiajie Li Naihong Yan Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China Research Laboratory of Ophthalmology West China HospitalSichuan UniversityChengdu610041China College of Biomedical Engineering Sichuan UniversityChengdu610041China

Choroidal neovascularization(CNV)is a common pathological feature of various eye diseases and an important cause of visual impairment in middle-aged and elderly patients.In previous studies,tetrahedral framework nucleic acids(tFNAs)showed good carrier performance.In this experiment,we developed microRNA-155-equipped tFNAs(T-155)and explored its biological effects on CNV.Based on the results of in-vitro experiments,T-155 could regulate macrophages into the antiangiogenic M1 type.Then,we injected T-155 into the vitreous of laser-induced CNV model mice and found that T-155 significantly reduced the size and area of CNV,inhibited blood vessel leakage.In summary,we prove that T-155 could regulate the inflammatory process of CNV by polarizing macrophages,thereby improving the symptoms of CNV.Thus,T-155 might become a new DNA-based drug with great potential for treating CNV.

关键词： Choroidal neovascularization Tetrahedral framework nucleic acid Macrophages MicroRNA-155 Immunity therapy

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Stimuli-responsive Nanoparticles for the Efficient Co-delivery of Chemotherapeutic Agents Doxorubicin and siPD-L1 to enhance the anti-tumor effect

Stimuli-responsive Nanoparticles for the Efficient Co-delive...

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2018年第十二届中国药物制剂大会

作者：周烨娟张学农苏州大学药学院

In this work, we designed dual pH/reduction sensitive nanoparticles, which were composed of polyL-lysine-lipoic acid（PLL-LA） as a reduction-responsive core, and modified with a tumor extracellular pH（pHe） triggered detachable PEG layer（sPEG） for the efficient co-delivery of doxorubicin（DOX） and PD-L1 siRNA（siPD-L1）. Under the physiological condition, the PEG layer was stable and led to prolonged circulation time. After accumulated in tumor sites, pHe-sensitive linkage between PEG layer and NPs degraded, which enhanced the internalization of NPs by tumor cells. Then, the high-concentration glutathione（GSH） within tumor cells triggered the destabilization of DOX-siPD-L1/sPEG-PLL-LA NPs, followed by rapid release of payloads DOX and siPD-L1 which diffused to nuclei and siPD-L1 in cytoplasm, respectively. Compared with that at p H 7.4, s PEG-PLL-LA NPs exhibited a higher cellular uptake and improved cytotoxicity against B16 cells in vitro at pH 6.5. Moreover, the sPEG NPs showed good tumor-targeting ability and excellent tumor-penetrating efficacy in tumor tissues. In conclusion, the sPEG modified NPs provided great potentials in cancer treatment.

关键词： PEGylation tumor acidity reduction sensitivity siRNA chemotherapy Immunity therapy

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Advances in targeted therapies for gastric cancer:a mini-review

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TMR Cancer 2020年第2期3卷 84-93页

作者： Xiao-Dong Wang Zhejiang University School of Medicine Second Affiliated Hospital Hangzhou 330102China

The incidence of gastric cancer ranks 4th in malignant tumors,and the mortality rate ranks 3rd in malignant tumors.Most patients with gastric cancer are already at the advanced stage when diagnosed.Although chemotherapy is the main treatment for patients with advanced gastric cancer,it can extend the overall survival.But adverse reactions are more prominent.With the rise of targeted therapy,the molecular mechanism of gastric cancer occurrence and development continues to develop,and molecular targeted therapy of gastric cancer has gradually emerged.The current targets for gastric cancer mainly include endothelial growth factor receptor,HER2,vascular endothelium growth factor,vascular endothelium growth factor receptor,mammalian rapamycin receptor,hepatocellular growth factor,et al.,but the clinical efficacy is still not satisfactory.At present,most of the studies on molecular targeted drugs for gastric cancer have ended in failure.The heterogeneity between patients and the prognosis of tumors in different parts may be different.It is suggested that screening targeted drugs according to the patient's pathological characteristics and molecular typing,and individualized treatment is the inevitable way of targeted treatment of gastric cancer.

关键词： Gastric cancer Targeted therapy Biomarker Immunity therapy Targeted drug

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