Tumor-Penetrating Peptide-Functionalized Redox-Responsive Hyperbranched Poly(amido amine) Delivering siRNA for Lung Cancer Therapy

Guo, Zhong; Li, Sha; Liu, Zonghua; Wang, Xue

doi:10.1021/acsbiomaterials.7b00971

Cited by 23 publications

(13 citation statements)

References 31 publications

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“…Guo et al constructed an siRNA-targeted delivery system based on hyperbranched poly(amidoamine) (PAA). [146] The tumor-penetrating internalized RGD (iRGD) peptide was conjugated to hyperbranched PAA via an amidation reaction. The iRGD peptide included tumor-specific RGD motif and CendR motif.…”

Section: Tumor-targeting Strategiesmentioning

confidence: 99%

Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Chen

Dong

Shi

2021

Adv Materials Technologies

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method clinically, however, it is accompanied by the inevitable side effects on normal tissues. [9] Similarly, other treatment methods have failed to achieve satisfactory treatment results in clinic. With the discovery of key oncogenic markers and pathways, gene therapy has become a novel class of pharmaceutical drugs and shown significant therapeutic advantages in fighting cancer. [10][11][12] Compared with chemotherapy, gene therapy has better selectivity and specificity for related genes.RNA interference (RNAi) is an important defense mechanism of eukaryotic cells, which inhibits the expression or transcription of specific genes by blocking their translation or transcription, so it is considered to be a revolutionary tool for mediating gene therapy. [13][14][15] Previous research has shown that RNAi can effectively modulating the expression of any gene involved in tumor initiation, growth, and metastasis formation. [16][17][18] MicroRNA (miRNA), small interfering RNA (siRNA), and short hairpin RNA (shRNA) are the major types of RNAi molecules, which can mediate RNAi and cause mRNA cleavage. [19] miRNA is an endogenous single-stranded RNA, which mainly acts on the 3'-untranslated region of target genes in the RNAi pathway. [20] While siRNA is a double-stranded RNA (dsRNA) which can be transfected into the human body and act on any part of mRNA. [21] shRNA can be cloned into an expression vector and express siRNA. [22] siRNA has powerful specific RNAi triggering activity, so it shows great potential in nucleic acid therapy. [23] siRNA is a 20-25 base pair nucleic acid fragment that can degrade messenger RNA (mRNA) in the cytoplasm and interfere with the expression of specific genes. [24][25][26] The mechanism of siRNA-mediated RNAi action is shown in Figure 1. siRNA is synthesized and delivered into the cytoplasm, or generated by the endogenous Dicer-mediated dsRNA cleavage, then it can be incorporated into the RNA-induced silencing complex (RISC, a multi-protein complex). Then the sense strand (nonguiding strand) is cleaved by the Argonaute 2 (AGO2, an endonuclease of the RISC), while the antisense strand guides RISC toward the target mRNA with a complementary sequence, which is further cleaved by AGO2 into mRNA fragments. Subsequently, the mRNA fragments are degraded by cellular exonuclease. In addition, the antisense strand-RISC complex is capable of being recycled, so effectively preventing the translation of target mRNA into proteins.RNA interference (RNAi), which can inhibit the expression or transcription of specific genes, is considered to be a revolutionary tool for mediating gene therapy. Small interfering RNA (siRNA) is an important therapeutic agent for RNAi. However, the clinical application of siRNA-based gene silencing is still limited due to the easy degradation of siRNA during the circulation in the body and the difficulty in delivering siRNA to desired tissues and cells. The rapid development of nanotechnology provides new ideas for siRNA delivery and a large variety of nanocarriers have been d...

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Section: Tumor-targeting Strategiesmentioning

confidence: 99%

Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Chen

Dong

Shi

2021

Adv Materials Technologies

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“…Therefore, the fluorescence intensity of the tumor spheroids in Lf modified liposomes group was weak. In addition, RGD is a member of tumor-penetrating peptide homes, can be effectively used to deliver agents or drugs into tumor [ 32 , 33 ]. So RGD can promote the penetration of RGD modified liposomes into the deep part of tumor spheroids, and RGD modification plays a dominating role on promoting the penetration of tumor spheroids.…”

Section: Resultsmentioning

confidence: 99%

Combined integrin αvβ3 and lactoferrin receptor targeted docetaxel liposomes enhance the brain targeting effect and anti-glioma effect

Zhang

Zhou

et al. 2021

J Nanobiotechnol

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The integrin αvβ3 receptor and Lactoferrin receptor (LfR) are over-expressed in both cerebral microvascular endothelial cells and glioma cells. RGD tripeptide and Lf can specifically bind with integrin αvβ3 receptor and LfR, respectively. In our study, RGD and Lf dual-modified liposomes loaded with docetaxel (DTX) were designed to enhance the brain targeting effect and treatment of glioma. Our in vitro studies have shown that RGD-Lf-LP can significantly enhance the cellular uptake of U87 MG cells and human cerebral microvascular endothelial cells (hCMEC/D3) when compared to RGD modified liposomes (RGD-LP) and Lf modified liposomes (Lf-LP). Free RGD and Lf competitively reduced the cellular uptake of RGD-Lf-LP, in particular, free RGD played a main inhibitory effect on cellular uptake of RGD-Lf-LP in U87 MG cells, yet free Lf played a main inhibitory effect on cellular uptake of RGD-Lf-LP in hCMEC/D3 cells. RGD-Lf-LP can also significantly increase penetration of U87 MG tumor spheroids, and RGD modification plays a dominating role on promoting the penetration of U87 MG tumor spheroids. The results of in vitro BBB model were shown that RGD-Lf-LP-C6 obviously increased the transport of hCMEC/D3 cell monolayers, and Lf modification plays a dominating role on increasing the transport of hCMEC/D3 cell monolayers. In vivo imaging proved that RGD-Lf-LP shows stronger targeting effects for brain orthotopic gliomas than that of RGD-LP and Lf-LP. The result of tissue distribution confirmed that RGD-LF-LP-DTX could significantly increase brain targeting after intravenous injection. Furthermore, RGD-LF-LP-DTX (a dose of 5 mg kg−1 DTX) could significantly prolong the survival time of orthotopic glioma-bearing mice. In summary, RGD and LF dual modification are good combination for brain targeting delivery, RGD-Lf-LP-DTX could enhance brain targeting effects, and is thus a promising chemotherapeutic drug delivery system for treatment of glioma. Graphical abstract

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“… 5 Short interfering RNA (siRNA) technology is one of the most effective options for cancer therapy. 6 Viruses were usually applied to deliver siRNA in the previous studies. 7 Nevertheless, viral carriers had the risk of immunogenicity and insertional mutagenesis.…”

Section: Introductionmentioning

confidence: 99%

<p>Silencing of MEF2D by siRNA Loaded Selenium Nanoparticles for Ovarian Cancer Therapy</p>

Wang¹,

Xia²,

Huo³

et al. 2020

IJN

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Background: Delivery of therapeutic small interfering RNA (siRNA) via functionalized nanoparticles holds great promise for cancer therapy. However, developing a safe and efficient delivery carrier of siRNA is a challenging issue. Methods: RGDfC peptide was used to modify the surface of selenium nanoparticles (SeNPs) to synthesize a biocompatible siRNA delivery vehicle (R-SeNPs), and MEF2D-siRNA was loaded onto R-SeNPs to prepare a functionalized selenium

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Tumor-Penetrating Peptide-Functionalized Redox-Responsive Hyperbranched Poly(amido amine) Delivering siRNA for Lung Cancer Therapy

Cited by 23 publications

References 31 publications

Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Combined integrin αvβ3 and lactoferrin receptor targeted docetaxel liposomes enhance the brain targeting effect and anti-glioma effect

<p>Silencing of MEF2D by siRNA Loaded Selenium Nanoparticles for Ovarian Cancer Therapy</p>

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