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An ionizable supramolecular dendrimer nanosystem for effective siRNA delivery with a favorable safety profile

Nano Research 2021年第7期14卷 2247-2254页

作者： Dinesh Dhumal Wenjun Lan Ling Ding Yifan Jiang Zhenbin Lyu erik laurini Domenico Marson Aura Tintaru Nelson Dusetti Suzanne Giorgio Juan Lucio Iovanna Sabrina Pricl Ling Peng Aix-Marseille Université CNRSCentre Interdisciplinaire de Nanoscience de Marseille(CINaM)UMR 7325Equipe Labellisée Ligue Contre le CancerMarseille 13288France Aix-Marseille Université INSERMCNRSInstitut Paoli-CalmettesCentre de Recherche en Cancérologie de Marseille(CRCM)Marseille 13288France Aix-Marseille Université CNRSCentre de Résonance Magnétique Biologique et Médicale(CRMBM)UMR 7339Marseille 13385France Aix-Marseille Université CNRSInstitut de Chimie Radicalaire(ICR)UMR 7273Marseille 13013France Molecular Biology and Nanotechnology Laboratory Department of Engineering and ArchitecturesUniversity of TriesteTrieste 34127Italy Department of General Biophysics Faculty of Biology and Environmental ProtectionUniversity of LodzLodz 90-136Poland

Gene therapy using small interfering RNA(siRNA)is emerging as a novel therapeutic approach to treat various ***,safe and efficient siRNA delivery still constitutes the major obstacle for clinical implementation of siRNA *** we report an ionizable supramolecular dendrimer vector,formed via self-assembly of a small amphiphilic dendrimer,as an effective siRNA delivery system with a favorable safety *** virtue of the ionizable tertiary amine terminals,the supramolecular dendrimer has a low positively charged surface potential and no notable cytotoxicity at physiological ***,this ionizable feature imparted sufficient surface charge to the supramolecular dendrimer to enable formation of a stable complex with siRNA via electrostatic *** resulting siRNA/dendrimer delivery system had a surface charge that was neither neutral,thus avoiding aggregation,nor too high,thus avoiding cytotoxicity,but was sufficient for favorable cellular uptake and endosomal release of the *** tested in different cancer cell lines and patient-derived cancer organoids,this dendrimer-mediated siRNA delivery system effectively silenced the oncogenes Myc and Akt2 with a potent antiproliferative effect,outperforming the gold standard vector,Lipofectamine ***,this ionizable supramolecular dendrimer represents a promising vector for siRNA *** concept of supramolecular dendrimer nanovectors via self-assembly is new,yet easy to implement in practice,offering a new perspective for supramolecular chemistry in biomedical applications.

关键词： dendrimer self-assembly ionizable vector siRNA delivery gene silencing non-viral vector

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A self-assembling prodrug nanosystem to enhance metabolic stability and anticancer activity of gemcitabine

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Chinese Chemical Letters 2022年第5期33卷 2481-2485页

作者： Mei Cong Guangling Xu Shaoyou Yang Jing Zhang Wenzheng Zhang Dinesh Dhumal erik laurini Kaiyue Zhang Yi Xia Sabrina Pricl Ling Peng Weidong Zhao School of Pharmacy Xinxiang Medical UniversityXinxiang 453003China Henan Key Laboratory of Immunology and Targeted Drugs School of Laboratory MedicineXinxiang Medical UniversityXinxiang 453003China Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine School of Laboratory MedicineXinxiang Medical UniversityXinxiang 453003China Aix-Marseille Université CNRSCenter Interdisciplinaire de Nanoscience de MarseilleUMR 7325Equipe Labellisépar La LigueMarseille 13288France Chongqing Key Laboratory of Natural Product Synthesis and Drug Research School of Pharmaceutical SciencesChongqing UniversityChongqing 401331China Molecular Biology and Nanotechnology Laboratory Department of Engineering and ArchitectureUniversity of TriesteTrieste 34127Italy Department of General Biophysics Faculty of Biology and Environmental ProtectionUniversity of LodzLodz 90-236Poland

Self-assembly is a powerful approach in molecular engineering for biomedical applications,in particu-lar for creating self-assembling ***,we report a self-assembling prodrug of the anticancer drug gemcitabine(Gem)based on amphiphilic dendrimer *** prodrug reported in this study demonstrates high drug loading(40%)and robust ability to self-assemble into small nanomicelles,which increase the metabolic stability of Gem and enable entry into cells via endocytosis,hence bypassing transport-mediated *** addition,this prodrug nanosystem exhibited an effective pH-and enzyme-responsive release of Gem,resulting in enhanced anticancer activity and reduced *** ad-vantageous features of both prodrug-and nanotechnology-based drug delivery,this self-assembling Gem prodrug nanosystem constitutes a promising anticancer *** study also offers new perspectives of the amphiphilic dendrimer nanoplatforms for the development of self-assembling prodrugs.

关键词： Self-assembling prodrug Gemcitabine Amphiphilic dendrimer Anticancer candidate Nanomicelles

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