title: Assembling Mn:ZnSe quantum dots-siRNA nanoplexes for gene silencing in tumor cells.
abstract: In this work, we demonstrate the use of manganese doped zinc selenide QDs (Mn:ZnSe d-dots) for gene delivery in vitro. Specifically, the d-dots were prepared as nanoplexes for facilitating the intracellular delivery of small interfering RNA (siRNA) molecules to pancreatic cancer cells (Panc-1), thereby inducing sequence-specific silencing of oncogenic K-Ras mutations in pancreatic carcinoma. For nanoplex preparation, a layer-by-layer (LBL) assembling method was adopted to modify the d-dot surface with cationic polymer poly(allylamine hydrochloride) (PAH) or polyethylenimine (PEI) for generating positive surface potential for complexing with K-Ras siRNA molecules. Owing to the unique and stable PL properties of the d-dots, siRNA transfection and the subsequent intracellular release profile from the d-dot/polymer-siRNA nanoplexes were monitored by fluorescence imaging. Quantitative results from flow cytometry study suggested that a high gene transfection efficiency was achieved. The expression of the mutant K-Ras mRNA in Panc-1 cells was observed to be significantly suppressed upon transfecting them with the nanoplex formulation. More importantly, cell viability studies showed that the d-dot/PAH nanoplexes were biocompatible and non-toxic even at concentrations as high as 160 μg mL(-1). Furthermore, the amine-terminated surface could be further modified to obtain multiple bio-functions. Based on these results, we envision that the designed d-dot nanoplexes can be developed as a flexible nanoplatform for both fundamental and practical clinical research applications.
authors.affiliation: School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore. ktyong@ntu.edu.sg.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Chengbin
authors.initials: C
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.forename: Hui Ting
authors.initials: HT
authors.lastname: Toh
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Guimiao
authors.initials: G
authors.lastname: Lin
authors.forename: Feng
authors.initials: F
authors.lastname: Yin
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
authors.forename: Ken-Tye
authors.initials: KT
authors.lastname: Yong
mesh_terms: D045744:Cell Line, Tumor; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008345:Manganese / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics*; D011073:Polyamines / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D045663:Quantum Dots / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D018036:Selenium Compounds / Q000737:chemistry*; D014162:Transfection; D017967:Zinc Compounds / Q000737:chemistry*
chemical_list: D011073:Polyamines; D034741:RNA, Small Interfering; D018036:Selenium Compounds; D017967:Zinc Compounds; C063994:polyallylamine; D008345:Manganese; D011094:Polyethyleneimine; C044696:zinc selenide