Molecular recognition enables nanosubstrate-mediated delivery of gene-encapsulated nanoparticles with high efficiency.
Substrate-mediated gene delivery is a promising method due to its unique ability to preconcentrate exogenous genes onto designated substrates. However, many challenges remain to enable continuous and multiround delivery of the gene using the same substrates without depositing payloads and immobilizing cells in each round of delivery. Herein we introduce a gene delivery system, nanosubstrate-mediated delivery (NSMD) platform, based on two functional components with nanoscale features, including (1) DNA⊂SNPs, supramolecular nanoparticle (SNP) vectors for gene encapsulation, and (2) Ad-SiNWS, adamantane (Ad)-grafted silicon nanowire substrates. The multivalent molecular recognition between the Ad motifs on Ad-SiNWS and the β-cyclodextrin (CD) motifs on DNA⊂SNPs leads to dynamic assembly and local enrichment of DNA⊂SNPs from the surrounding medium onto Ad-SiNWS. Subsequently, once cells settled on the substrate, DNA⊂SNPs enriched on Ad-SiNWS were introduced through the cell membranes by intimate contact with individual nanowires on Ad-SiNWS, resulting in a highly efficient delivery of exogenous genes. Most importantly, sequential delivery of multiple batches of exogenous genes on the same batch cells settled on Ad-SiNWS was realized by sequential additions of the corresponding DNA⊂SNPs with equivalent efficiency. Moreover, using the NSMD platform in vivo, cells recruited on subcutaneously transplanted Ad-SiNWS were also efficiently transfected with exogenous genes loaded into SNPs, validating the in vivo feasibility of this system. We believe that this nanosubstrate-mediated delivery platform will provide a superior system for in vitro and in vivo gene delivery and can be further used for the encapsulation and delivery of other biomolecules.
School of Biomedical Engineering, MED-X Research Institute, Shanghai Jiao Tong University , Shanghai 200030, China.
Jinliang
J
Peng
Mitch André
MA
Garcia
Jin-sil
JS
Choi
Libo
L
Zhao
Kuan-Ju
KJ
Chen
James R
JR
Bernstein
Parham
P
Peyda
Yu-Sheng
YS
Hsiao
Katherine W
KW
Liu
Wei-Yu
WY
Lin
April D
AD
Pyle
Hao
H
Wang
Shuang
S
Hou
Hsian-Rong
HR
Tseng
D020816:Amino Acid Motifs; D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008027:Light; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D012542:Scattering, Radiation; D047392:beta-Cyclodextrins / Q000737:chemistry
D047392:beta-Cyclodextrins; C031215:betadex