Single-component self-assembled RNAi nanoparticles functionalized with tumor-targeting iNGR delivering abundant siRNA for efficient glioma therapy

An, Sai; Jiang, Xinru; Shi, Jiashu; He, Xi; Li, Jianfeng; Guo, Yubo; Zhang, Yu; Ma, Haojun; Lü, Yifei; Jiang, Chen

doi:10.1016/j.biomaterials.2015.02.084

Cited by 44 publications

(35 citation statements)

References 41 publications

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“…As mentioned above and the previous studies [25,37,38], iNGR has been demonstrated to enhance cancer cell-specific internalization of nanoparticles. Moreover, nanorods have a larger surface/volume ratio than nanospheres, improving the concentration of iNGR per unit volume of LProd.…”

Section: Resultsmentioning

confidence: 53%

“…Besides, iNGR and the flexible ellipse conformation can also endow the LProd with high specificity of cancer cells. First, CD13 has been demonstrated to be selectively overexpressed in tumor vascular cells and tumor cells [25,37,38]. Second, iNGR can be specifically proteolytically cleaved by a tumor-host protease to exposes the CendR motif, thereby avoiding the activation of internalization process in normal vasculature [25].…”

Section: Lprod Specifically Internalize Into Cancer Cells Via Ingr-mediated Cellular Uptakementioning

confidence: 99%

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A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties

Yan

Wang

et al. 2019

Biomaterials

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Nanostructures formed with bioactive peptides offer an exciting prospect in clinical oncology as a novel class of therapeutic agents for human cancers. Despite their therapeutic potential, however, peptide-based nanomedicines are often inefficacious in vivo due to low cargo-loading efficiency, poor tumor cell-targeting specificity and limited drug accumulation in tumor tissues. Here, we describe the design, via assembly of a p53-activating peptide termed PMI, functionalized PEG and fluorescent lanthanide oxyfluoride nanocrystals, of a novel nanotheranostic shaped in flexible rods. This lanthanide-peptide nanorod or LProd of bionic nature exhibited significantly enhanced tumor-targeting and -imaging properties compared to its spherical counterpart. Importantly, LProd potently inhibited tumor growth in a mouse model of human colon cancer through activating tumor suppressor protein p53 via MDM2/MDMX antagonism, while maintaining a highly favorable biosafety profile. Our data demonstrate that LProd as a multifunctional theranostic platform is ideally suited for tumor-specific peptide drug delivery with real-time disease tracking, thereby broadly impacting clinical development of antitumor peptides.

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Section: Resultsmentioning

confidence: 53%

Section: Lprod Specifically Internalize Into Cancer Cells Via Ingr-mediated Cellular Uptakementioning

confidence: 99%

A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties

Yan

Wang

et al. 2019

Biomaterials

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“…pOEI was previously proved to be GSH responsive at the intracellular GSH concentration of 10 × 10 −3 m . After the incubation of 3CDIT‐targeting pOEI/DOX/ATP aptamer NPs in presence of 10 × 10 −3 m GSH and then 1 × 10 −3 m ATP, significant DOX release were observed (Figure C).…”

Section: Resultsmentioning

confidence: 79%

“…pOEI ( M w 10 000 g mol −1 ) is a GSH‐responsive and positively charged polymer, which was originally designed and synthesized in our previous research . This is the first time for pOEI to be used for chemotherapeutic drug delivery.…”

Section: Resultsmentioning

confidence: 99%

Amino Acid Metabolism Abnormity and Microenvironment Variation Mediated Targeting and Controlled Glioma Chemotherapy

Zhao

et al. 2016

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Energy metabolism abnormity is one of the most significant hallmarks of cancer. As a result, large amino acid transporter 1 (LAT1) is remarkably overexpressed in both blood-brain-barrier and glioma tumor cells, leading a rapid and sufficient substrate transportation. 3CDIT and 4CDIT are originally synthesized by modifying the existing most potent LAT1 substrate. 3CDIT is selected as its higher glioma-targeting ability. Since the microenvironment variation in tumor cells is another important feature of cancer, a great disparity in adenosine-5'-triphosphate (ATP) and glutathione (GSH) levels between extracellular and intracellular milieu can provide good possibilities for dual-responsive drug release in tumor cells. Doxorubicin (DOX) is successfully intercalated into the ATP aptamer DNA scaffolds, compressed by GSH-responsive polymer pOEI, and modified with 3CDIT to obtain 3CDIT-targeting pOEI/DOX/ATP aptamer nanoparticles (NPs). Enhanced NP accumulation and rapid GSH & ATP dual-responsive DOX release in glioma are demonstrated both in vitro and in vivo. More efficient therapeutic effects are shown with 3CDIT-targeting pOEI/DOX/ATP aptamer NPs than free DOX and no systemic toxicity is observed. Therefore, glioma-targeting delivery and GSH & ATP dual-responsive release guarantee an adequate DOX accumulation within tumor cells and ensure a safe and efficient chemotherapy for glioma.

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“…Each nanosphere contains about a half million tandem copies of therapeutic RNA strands which are cleavable with dicer. Moreover, these RNA strands were layers of parcels with each other, so they have significantly better stability than single-stranded RNA18., 19.. RCT offered an option to delivery RNA drugs efficiently and therefore has been adopted to construct valid siRNA delivery system in general.…”

Section: Introductionmentioning

confidence: 99%

GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy

Guo

Chen

et al. 2019

Acta Pharmaceutica Sinica B

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Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.

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Single-component self-assembled RNAi nanoparticles functionalized with tumor-targeting iNGR delivering abundant siRNA for efficient glioma therapy

Cited by 44 publications

References 41 publications

A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties

A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties

Amino Acid Metabolism Abnormity and Microenvironment Variation Mediated Targeting and Controlled Glioma Chemotherapy

GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy

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