Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

Abstract

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.

Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

“…Taken the transfection efficiency and MFI of the GFP positive cells into consideration, the ratio of N/P of 5 was selected for future studies. The difference between the percentage of transfected cells and the MFI of transfected cells was consistent with previously reported results ( McLenachan et al, 2013 ; Avci-Adali et al, 2014 ; Lee et al, 2015 ; Li et al, 2017a ). Transfection using the same transfection reagent led to similar transfection efficiency but not the MFI ( Figures 4D,E ) with the increase of the incubation time, which was consistent with previously report ( Avci-Adali et al, 2014 ).…”

TRAIL-based gene delivery and therapeutic strategies

“…Systemic injection of the proapoptotic mTRAIL plasmid by RRPHC ternary complexes inhibited the melanoma growth, without noticeable side toxicity. Next, this group reported a similar system of an artificial virus core-shell to target cancer stem cell-like cells [77]. The intravenously injected nanoparticles accumulated at the tumor sites while reducing the exposure to the normal tissues, and efficiently arrest the tumor growth, without obvious systemic toxicity.…”

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

“…Following the building criteria for multifunctional nucleus‐targeted gene carriers, Gong and co‐workers designed and constructed a “core–shell” ternary nanoparticle with hierarchical targeting as well as depth penetration capacity for in vivo gene therapy . As depicted in Figure a, a spontaneous nucleus‐targeting binary core (PF 33 /pDNA), which was formed by condensing plasmid DNA with fluorinated polymers (PFs), was covered by a negatively charged capsid‐like shell (RGD‐R8‐PEG‐HA, RRPH).…”

“…c) Tumor growth curves of HCT 116 tumor‐bearing nude mice after treatment with different formulations. a–c) Adapted with permission . Copyright 2017, Ivyspring International Publisher.…”