Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy

Xia, Yu; Xu, Tiantian; Wang, Changbing; Li, Yinghua; Lin, Zhengfang; Zhao, Mingqi; Zhu, Bing

doi:10.2147/ijn.s148960

Cited by 72 publications

(49 citation statements)

References 35 publications

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“…19 Nevertheless, there is still some deficiency in such delivery vehicle for effectively carrying the genes, such as the lack of active tumor-targeting activity. 20 In the past decade, many tumor-targeting molecules have been introduced to endow NPs with active targeting ability. 21 Recently, hyaluronic acid (HA) as an active tumor-targeting moiety has achieved more attention in the field of targeting delivery carriers.…”

Section: Introductionmentioning

confidence: 99%

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

Xia¹,

Guo²,

Xu³

et al. 2018

IJN

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Background Small interfering RNA (siRNA) as a new therapeutic modality holds promise for cancer treatment. However, the traditional viral carriers are prone to immunogenicity and risk of insertional mutagenesis. Methods In order to provide a tumor-targeted delivery carrier of siRNA in cancer therapy, the hyaluronic acid (HA)-selenium (Se)-polyethylenimine (PEI) nanoparticle (NP) was fabricated by decorating SeNP with HA as a tumor-targeting moiety and by linking the polycationic polymers polyethylenimine PEI onto the surface of SeNP. The siRNA was loaded to the surface of SeNP HA-Se-PEI via the electrostatic interaction between siRNA and PEI to prepare the functionalized SeNP HA-Se-PEI@siRNA. Results The HA-Se-PEI@siRNA was internalized into the HepG2 cell mainly in a clathrin-mediated endocytosis manner. Owing to the active tumor-targeted effect mediated by HA, HA-Se-PEI@siRNA achieved the obvious higher transfection efficiency, greater gene silencing ability, and stronger cytotoxicity in the HepG2 cell compared with the passive tumor-targeted NP Se-PEI@siRNA. The knockdown of hairy and enhancer of split 5 by HA-Se-PEI@siRNA induced the HepG2 cell cycle arrest at the G0/G1 phase and apoptosis. Furthermore, the treatment with HA-Se-PEI@siRNA resulted in greater antitumor efficacy compared with the Se-PEI@siRNA in vitro and in vivo. In addition, the HA-Se-PEI@siRNA was almost no toxic to the key organs of mice. Conclusion These findings provided an alternative therapeutic route for targeted cancer treatments.

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Section: Introductionmentioning

confidence: 99%

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

Xia¹,

Guo²,

Xu³

et al. 2018

IJN

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“…Endocytosis is an important transport mechanism for nanoparticles across the membrane [30]. An uptake inhibition assay was performed to investigate the uptake pathways of HA-Se@PTX.…”

Section: Selective Uptake Of Ha-se@ptx Nanoparticlesmentioning

confidence: 99%

Hyaluronic acid-modified selenium nanoparticles for enhancing the therapeutic efficacy of paclitaxel in lung cancer therapy

Zou

Chen

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. In this paper, selenium nanoparticles (SeNPs) was linked with hyaluronic acid (HA) to prepare tumor-targeted delivery vehicle HA-SeNPs, and HA-SeNPs was loaded with paclitaxel (PTX) to fabricate functionalized selenium nanoparticles HA-Se@PTX. HA-Se@PTX showed greater uptake in A549 cells in comparison with that in HUVEC, verifying HA-mediated specific uptake of HA-Se@PTX. HA-Se@PTX was capable of entering A549 cells via clathrin-associated endocytosis and showed faster drug release in cancer cell microenvironment in comparison with normal physiological environment. HA-Se@PTX could obviously inhibit the proliferation, migration and invasion of A549 cells and trigger A549 cells apoptosis. Moreover, active targeting functionalized selenium nanoparticles HA-Se@PTX showed greater in vivo antitumor activity compared with free PTX or passive targeting delivery system Se@PTX. In addition, HA-Se@PTX exhibited negligible toxicity on the major organs of mice. In a word, HA-Se@PTX may develop into a valuable nanoscale antitumor drug agent for lung cancer treatment.

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“…The in vitro release profile of oseltamivir from SeNPs@OT was investigated by dialysis method [23]. In brief, 2 mg SeNPs@OT was dissolved in water and introduced into the dialysis tube.…”

Section: In Vitro Oseltamivir Releasementioning

confidence: 99%

Functionalized selenium nanoparticles enhance the anti-EV71 activity of oseltamivir in human astrocytoma cell model

Zhong

Xia

Hua

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Enterovirus 71 (EV71) which commonly caused the hand-foot-mouth disease (HFMD) has become one of public health challenges worldwide. However, no effective vaccines or drugs for this disease has been developed. Thus, there is an urgent need to find a new strategy for treating the EV71 infection. Oseltamivir (OT) is an effective antiviral agent, but continuous use of oseltamivir leads to a diminished therapeutic effect in the clinic. In order to improve the antiviral activity of oseltamivir, oseltamivir was loaded onto surfaces of selenium nanoparticles (SeNPs) to fabricate a functionalized antiviral nanoparticles SeNPs@OT. The size of SeNPs@OT was tested by TEM and dynamic light scattering. The chemical structure and elemental composition of SeNPs@OT were analyzed by FT-IR and EDX, respectively. SeNPs@OT exhibited good stability and effective drug release in serum and PBS. SeNPs@OT efficiently entered into human astrocyte U251 cells (host cells) via clathrin-associated endocytosis and inhibited EV71 proliferation, which could protect EV71-infected U251 cells from apoptosis through mitochondrial pathway. Furthermore, SeNPs@OT inhibited EV71 activity probably by reducing the generation of reactive oxygen species in EV71-infected U251 cells. Interestingly, SeNPs obviously enhanced antiviral activity of oseltamivir in the anti-EV71 cell model. Taken together, SeNPs@OT is a promising antiviral drug candidate for EV71 infection.

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Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy

Cited by 72 publications

References 35 publications

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy

Hyaluronic acid-modified selenium nanoparticles for enhancing the therapeutic efficacy of paclitaxel in lung cancer therapy

Functionalized selenium nanoparticles enhance the anti-EV71 activity of oseltamivir in human astrocytoma cell model

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