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2017 ; 7
(6
): 1633-1649
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Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection
Efficiency for In Vivo Gene Therapy
#MMPMID28529641
Li L
; Li X
; Wu Y
; Song L
; Yang X
; He T
; Wang N
; Yang S
; Zeng Y
; Wu Q
; Qian Z
; Wei Y
; Gong C
Theranostics
2017[]; 7
(6
): 1633-1649
PMID28529641
show ga
Cancer stem cell-like cells (CSCL) are responsible for tumor recurrence
associated with conventional therapy (e.g. surgery, radiation, and chemotherapy).
Here, we developed a novel multifunctional nucleus-targeting nanoparticle-based
gene delivery system which is capable of targeting and eradicating CSCL. These
nanoparticles can facilitate efficient endosomal escape and spontaneously
penetrate into nucleus without additional nuclear localization signal. They also
induced extremely high gene transfection efficiency (>95%) even in culture medium
containing 30% serum, which significantly surpassed that of some commercial
transfection reagents, such as Lipofectamine 2000 and Lipofectamine 3000 etc.
Especially, when loaded with the TRAIL gene, this system mediated remarkable
depletion of CSCL. Upon systemic administration, the nanoparticles accumulated in
tumor sites while sparing the non-cancer tissues and significantly inhibited the
growth of tumors with no evident systemic toxicity. Taken together, our results
suggest that these novel multifunctional, nucleus-targeting nanoparticles are a
very promising in vivo gene delivery system capable of targeting CSCL and
represent a new treatment candidate for improving the survival of cancer
patients.