Cell-Penetrating Poly(disulfide) Assisted Intracellular Delivery of Mesoporous Silica Nanoparticles for Inhibition of miR-21 Function and Detection of Subsequent Therapeutic Effects.
The design of drug delivery systems capable of minimal endolysosomal trapping, controlled drug release, and real-time monitoring of drug effect is highly desirable for personalized medicine. Herein, by using mesoporous silica nanoparticles (MSNs) coated with cell-penetrating poly(disulfide)s and a fluorogenic apoptosis-detecting peptide (DEVD-AAN), we have developed a platform that could be uptaken rapidly by mammalian cells via endocytosis-independent pathways. Subsequent loading of these MSNs with small molecule inhibitors and antisense oligonucleotides resulted in intracellular release of these drugs, leading to combination inhibition of endogenous miR-21 activities which was immediately detectable by the MSN surface-coated peptide using two-photon fluorescence microscopy.
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.|College of Materials Science & Engineering, South China University of Technology, Guangzhou, China.
Changmin
C
Yu
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
Linghui
L
Qian
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.|Institute of Bioengineering, Zhejiang University of Technology, Hangzhou, China.
Jingyan
J
Ge
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
Jiaqi
J
Fu
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
Peiyan
P
Yuan
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
Samantha C L
SC
Yao
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore. chmyaosq@nus.edu.sg.
Shao Q
SQ
Yao
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties
D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D004220:Disulfides; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D054852:Small Molecule Libraries; D012822:Silicon Dioxide
cell-penetrating poly(disulfide); drug delivery; endocytosis; nanoparticles; small-molecule inhibitor