A fluorinated low-molecular-weight PEI/HIF-1α shRNA polyplex system for hemangioma therapy

Guo, Xiaoshuang; Yuan, Zihan; Xu, Yu; Wei, Minyan; Fang, Zhiwei; Yuan, Weien

doi:10.1039/d0bm00171f

Cited by 15 publications

(11 citation statements)

References 53 publications

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“…These data indicated that the fluorinated LW‐PEI‐based cationic micelles mediated effective miRNA delivery to modulate the biological properties of NSCs via gene regulation. [ 25 ] We further conducted terminal deoxynucleotidyl transferase–mediated dUTP nick‐end labeling (TUNEL) assay to verify the apoptosis rate of NSCs under hypoxic conditions after miR‐210 upregulation. TUNEL analysis showed the apoptosis rate in vitro of miR mimi ‐SPIO/PEI‐F‐labeled NSCs was 11.9 ± 3.82%, which was markedly lower than that of unlabeled NSCs (24.82 ± 3.80%), Scr‐SPIO/PEI‐F‐labeled NSCs (23.69 ± 6.91%), and miR inh ‐SPIO/PEI‐F‐labeled NSCs (21.03 ± 3.60%) ( P < 0.05) (Figure 4d,e).…”

Section: Resultsmentioning

confidence: 99%

“…Fluorinated LW-PEI-based cationic micelles demonstrated effective gene delivery to target cells with high biosafety. [25] Thus, it seems to be an appropriate candidate mediating gene therapy to modulate the biological properties of NSCs. To obtain the miRNA-complexed MRI-visible nanomedicine, SPIO-loaded fluorinated LW-PEI (PEI-F) micelles (SPIO/PEI-F) were synthesized by self-assembly of SPIO and PEI-F. Then, miRNA was absorbed on the surface of the micelles via electrostatic interaction.…”

Section: Synthesis and Gene Transfer Of Theranostic Nanomedicinementioning

confidence: 99%

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Upregulating microRNA‐210 to Inhibit Apoptosis of Neural Stem Cells with an MRI–Visible Nanomedicine for Stroke Therapy

et al. 2022

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Transplantation of neural stem cells (NSCs) is a promising paradigm for treating stroke. However, the poor survival of transplanted NSCs greatly limits the therapeutic potential. microRNA‐210 (miR‐210), a key hypoxia‐regulated miRNA, can enhance cell survival by targeting the expression of multiple apoptosis‐related genes, such as caspase‐8‐associated protein‐2 (casp8ap2), Bax, and Bcl‐2. Meanwhile, a noninvasive cell‐tracking method is also indispensable for monitoring the in vivo cell‐based therapy. Herein, an MRI–visible nanomedicine is developed to codeliver superparamagnetic iron oxide (SPIO) nanoparticles and miR‐210 into NSCs. This therapeutic nanomedicine not only promotes the survival of NSCs via upregulating miR‐210 to inhibit NSCs apoptosis but also allows an in vivo tracking of transplanted NSCs with MRI. The enhanced NSCs survivability significantly promotes the structural and functional recovery after stroke onset, which highlights the great potential of the multifunctional nanomedicine to improve the therapeutic efficacy of NSCs for stroke treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Synthesis and Gene Transfer Of Theranostic Nanomedicinementioning

confidence: 99%

Upregulating microRNA‐210 to Inhibit Apoptosis of Neural Stem Cells with an MRI–Visible Nanomedicine for Stroke Therapy

et al. 2022

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“…One of the practical challenges we face is that the majority of cationic polymer vectors have low efficiency and are unsafe . Some studies have reported that the functional modification of LMW PEI can effectively improve its nucleic acid delivery with high safety. − For this reason, first, we synthesized RRCPP-based LMW PEI as a backbone and modified it with cholesterol, PEG, and RGD-conjugated R8. Due to PEG having the advantages of inhibiting the phagocytosis of phagocytes and prolonging the blood circulation time, PEGylation combined with cholesterol modification has long been a conventional means of nanoparticle development.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Melanoma by Nano-conjugate-Delivered Wee1 siRNA

et al. 2021

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Small interfering RNA (siRNA)-based drugs have shown tremendous potential to date in cancer gene therapy. Despite the considerable efforts in siRNA design and manufacturing, unsatisfactory delivery systems persist as a limitation for the application of siRNA-based drugs. In this work, the cholesterol, cell-penetrating peptide conjugate cRGD (R8–cRGD), and polyethylene glycol (PEG) were introduced into low-molecular-weight polyethyleneimine (LMW PEI) to form cRGD–R9–cholesterol–PEI–PEG (RRCPP) nanoparticles with specific targeting and highly penetrating abilities. The enhanced siRNA uptake efficiency of the RRCPP delivery system benefited from R8–cRGD modification. Wee1 is an oncogenic nuclear kinase that can regulate the cell cycle as a crucial G2/M checkpoint. Overexpression of Wee1 in melanoma may lead to a poor prognosis. In the present study, RRCPP nanoparticles were designed for Wee1 siRNA delivery to form an RRCPP/siWee1 complex, which significantly silenced the expression of the WEE1 gene (>60% inhibition) and induced B16 tumor cell apoptosis by abrogating the G2M checkpoint and DNA damage in vitro. Furthermore, the RRCPP/siWee1 complex suppressed B16 tumor growth in a subcutaneous xenograft model (nearly 85% inhibition rate) and lung metastasis (nearly 66% inhibition rate) with ideal in vivo safety. Briefly, our results support the validity of RRCPP as a potential Wee1 siRNA carrier for melanoma gene therapy.

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“…To address such problems, researchers have developed fluorinated polymeric carriers . Thanks to the strong hydrophobic and fluorophilic properties, fluorinated segments connected on the cationic polymers could stabilize polyplexes in physiological environments at low critical concentrations, defending them from destabilization caused by serum proteins and other negatively charged biomacromolecules. − At the same time, while fluoropolymers have shown bioinert and antifouling properties, fluorinated polyplexes have exhibited improved serum tolerance without decreasing transfection efficiency. − To deliver nucleic acids such as DNA, siRNA, miRNA, etc., synthetic modifications of polyamidoamine, poly(ethylenimine), poly(propylenimine), poly(amino ester), polypeptides, and many other dendrimers with fluorinated agents have been developed to produce cationic fluorinated carriers.…”

Section: Applicationsmentioning

confidence: 99%

Fluoropolymer Nanoparticles Synthesized via Reversible-Deactivation Radical Polymerizations and Their Applications

Zhang,

Chen,

Ameduri

et al. 2023

Chem. Rev.

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Fluorinated polymeric nanoparticles (FPNPs) combine unique properties of fluorocarbon and polymeric nanoparticles, which has stimulated massive interest for decades. However, fluoropolymers are not readily available from nature, resulting in synthetic developments to obtain FPNPs via free radical polymerizations. Recently, while increasing cutting-edge directions demand tailored FPNPs, such materials have been difficult to access via conventional approaches. Reversible-deactivation radical polymerizations (RDRPs) are powerful methods to afford well-defined polymers. Researchers have applied RDRPs to the fabrication of FPNPs, enabling the construction of particles with improved complexity in terms of structure, composition, morphology, and functionality. Related examples can be classified into three categories. First, well-defined fluoropolymers synthesized via RDRPs have been utilized as precursors to form FPNPs through self-folding and solution self-assembly. Second, thermally and photoinitiated RDRPs have been explored to realize in situ preparations of FPNPs with varied morphologies via polymerizationinduced self-assembly and cross-linking copolymerization. Third, grafting from inorganic nanoparticles has been investigated based on RDRPs. Importantly, those advancements have promoted studies toward promising applications, including magnetic resonance imaging, biomedical delivery, energy storage, adsorption of perfluorinated alkyl substances, photosensitizers, and so on. This Review should present useful knowledge to researchers in polymer science and nanomaterials and inspire innovative ideas for the synthesis and applications of FPNPs.

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A fluorinated low-molecular-weight PEI/HIF-1α shRNA polyplex system for hemangioma therapy

Abstract: RNAi technology targeting HIF-1α could benefit hemangioma therapy effectively and FPEI polyplexes which could inhibit the expression of HIF-1α at the translational level can provide a practicable strategy for clinical hemangioma treatment in the future.

Cited by 15 publications

References 53 publications

Upregulating microRNA‐210 to Inhibit Apoptosis of Neural Stem Cells with an MRI–Visible Nanomedicine for Stroke Therapy

Upregulating microRNA‐210 to Inhibit Apoptosis of Neural Stem Cells with an MRI–Visible Nanomedicine for Stroke Therapy

Treatment of Melanoma by Nano-conjugate-Delivered Wee1 siRNA

Fluoropolymer Nanoparticles Synthesized via Reversible-Deactivation Radical Polymerizations and Their Applications

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