Layer-by-layer siRNA/poly(L-lysine) Multilayers on Polydopamine-coated Surface for Efficient Cell Adhesion and Gene Silencing

Abstract

For tissue engineering applications, small interfering RNA (siRNA) is an attractive agent for controlling cellular functions and differentiation. Although polyionic condensation of nucleic acids with polycations has been widely used for gene delivery, siRNA is not strongly associated with cationic carriers due to its low charge density and rigid molecular structures. The use of an excess amount of cationic carriers is often used for siRNA condensation, though they can induce severe cytotoxicity. Here we introduce the self-assembly of siRNA with mild polyelectrolytes into multilayers for efficient gene silencing during cell proliferation. The multilayers were prepared through the sequential layer-by-layer deposition of siRNA and poly-L-lysine (PLL) on a polydopamine-coated substrate. The cells, grown on the siRNA/PLL multilayers, exhibited a remarkable inhibition of the expression of target genes as compared to the use of scrambled siRNA. The gene silencing efficiency depends on the number of siRNA layers within a multilayer. This result indicates that siRNA/PLL multilayers can be potentially utilized for efficient surface-mediated siRNA delivery.

Method and its Composition for encapsulation, stabilization, and delivery of siRNA in Anionic polymeric nanoplex: An In vitro- In vivo Assessment

“…There was some extent of success with viral vectors and lipidic transfecting reagents, however, either the safety concerns or the lack of in vivo fittingness discourages their clinical utilization. In this meadow, cationic polymeric systems were extensively utilized, however, the toxicity issues associated with them substantially impedes the further development 34,35 .…”

RETRACTED ARTICLE: Degradable poly-L-lysine-modified PLGA cell microcarriers with excellent antibacterial and osteogenic activity

“…PLL coating has been shown to facilitate the binding of bioactive factors and polymer materials [22]. This surface immobilization method has been applied to the controlled release and delivery of various bioactive factors, such as DNA, drugs, miRNA and nerve growth factor (NGF), [17,23,24]. Therefore, PLL coating not only is a surface modification method to enhance the bioactivity of cell microcarriers but also can provide an effective delivery carrier for growth factors.…”

3D printing of tissue engineering scaffolds: a focus on vascular regeneration

“…Besides, stimulation cues regulate cell growth [ 33 ]. The biochemical cues can be obtained by surface coating of scaffolds or products after degradation [ 34 , 35 ]. The biophysical cues (e.g., hardness, strain, hydrostatic pressure, shear stress, cyclic stress, and surface topology) can be given directly by scaffolds or with the help of external fields [ 36 , 37 ].…”

“…During fabrications of vascular scaffolds, auxiliary processes are used as a complement to the forming processes. There are three aspects usually involved using auxiliary materials: (i) chemical modification [ 78 ] and physical modification [ 75 ] of printing materials; (ii) printing processes [ 22 , 23 , 79 ]; and (iii) post-treatment processes [ 34 , 71 ]. Some materials such as methacrylate, GMA, and magnesium chloride hexahydrate are utilized for chemical modification [ 35 , 78 ].…”

“…Besides, auxiliary materials are involved in post-treatment processes. Coated materials such as poly- l -lysine [ 34 ] were reported. These materials improve the properties of scaffolds and contribute to their functionalization.…”