Membrane-destabilizing ionizable lipid empowered imaging-guided siRNA delivery and cancer treatment.

Autor: Guo S; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China., Li K; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China., Hu B; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China., Li C; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China., Zhang M; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China., Hussain A; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China., Wang X; Institute of Molecular Medicine, College of Future Technology Peking University Beijing P. R. China., Cheng Q; Department of Biochemistry Simmons Comprehensive Cancer Center The University of Texas Southwestern Medical Center Dallas Texas USA., Yang F; Howard Hughes Medical Institute, Department of Medicine, School of Medicine University of California, San Diego La Jolla California USA., Ge K; Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education Hebei University Baoding P. R. China., Zhang J; Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education Hebei University Baoding P. R. China., Chang J; School of Life Sciences, Tianjin Engineering Center of Micro Nano Biomaterials and Detection Treatment Technology Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University Tianjin P. R. China., Liang XJ; Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology Beijing P. R. China., Weng Y; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China., Huang Y; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Institute of Engineering Medicine Beijing Institute of Technology Beijing P. R. China.
Jazyk: angličtina
Zdroj: Exploration (Beijing, China) [Exploration (Beijing)] 2021 Sep 01; Vol. 1 (1), pp. 35-49. Date of Electronic Publication: 2021 Sep 01 (Print Publication: 2021).
DOI: 10.1002/EXP.20210008
Abstrakt: One of the imperative medical requirements for cancer treatment is how to establish an imaging-guided nanocarrier that combines therapeutic and imaging agents into one system. siRNA therapeutics have shown promising prospects in controlling life-threatening diseases. However, it is still challenging to develop siRNA formulations with excellent cellular entry capability, efficient endosomal escape, and simultaneous visualization. Herein, we fabricated multifunctional ionizable lipid nanoparticles (iLNPs) for targeted delivery of siRNA and MRI contrast agent. The iLNPs comprises DSPC, cholesterol, PEGylated lipid, contrast agent DTPA-BSA (Gd), and ionizable lipid termed iBL0104. siRNA-loaded iLNPs (iLNPs/siRNA) could be decorated with a tumor targeting cyclic peptide (c(GRGDSPKC)) (termed GARP), or without targeting modification (termed GAP). Data revealed that GARP/siRNA iLNPs exhibited significantly higher cellular entry efficiency than GAP/siRNA iLNPs. GARP/siRNA iLNPs rapidly and effectively escaped from endosome and lysosome after internalization. Compared with GAP/siPLK1, GARP/siPLK1 exhibited better tumor inhibition efficacy in both cell-line derived xenograft and liver cancer patient derived xenograft murine models. In addition, GARP formulation displayed ideal MRI effect in tumor-bearing mice, and was well tolerated by testing animals. Therefore, this study provides an excellent example for achieving imaging-guided and tumor-targeted siRNA delivery and cancer treatment, highlighting its promising potential for translational medicine application.
Competing Interests: S.G. and Y.H. declare that a patent relative the study has been filed. The remaining authors declare no competing interests.
(© 2021 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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