Identification and optimization of tunable endosomal escape parameters for enhanced efficacy in peptide-targeted prodrug-loaded nanoparticles

Nanoscale ◽  
2022 ◽  
Author(s):  
Franklin Mejia ◽  
Sabrina Khan ◽  
David T. Omstead ◽  
Christina Minetos ◽  
Basar Bilgicer
Keyword(s):  
Endosomal Escape

Endosomal escape of nanoparticles (NPs) is a weighty consideration for engineering successful nanomedicines.

Delivery of Cas13a/crRNA by self-degradable black phosphorus nanosheets to specifically inhibit Mcl-1 for breast cancer therapy

2020 ◽  
Vol 8 (48) ◽  
pp. 11096-11106
Author(s):  
Huahua Yue ◽  
Ru Huang ◽  
Yuanyue Shan ◽  
Da Xing
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Black Phosphorus ◽  
Endosomal Escape ◽  
Transcriptional Level ◽  
Breast Cancer Therapy

The constructed Cas13a/crRNA complex is delivered into cytoplasm by PBP via endocytosis, followed by endosomal escape based on biodegradation of the PBP, and efficiently knocked down Mcl-1 at transcriptional level for breast cancer therapy.

Intracellular KRAS-specific antibody enhances the anti-tumor efficacy of gemcitabine in pancreatic cancer by inducing endosomal escape

2021 ◽  
Author(s):  
Ji Eun Lee ◽  
Yeo Wool Kang ◽  
Kyung Hee Jung ◽  
Mi Kwon Son ◽  
Seung-Min Shin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Specific Antibody ◽  
Endosomal Escape

Application of chloroquine as an endosomal escape enhancing agent: new frontiers for an old drug

2021 ◽  
pp. 1-13
Author(s):  
Mohammad Hajimolaali ◽  
Hosein Mohammadian ◽  
Ali Torabi ◽  
Amin Shirini ◽  
Mostafa Khalife Shal ◽  
...  
Keyword(s):  
Endosomal Escape

scholarly journals Illuminating endosomal escape of polymorphic lipid nanoparticles that boost mRNA delivery

2021 ◽  
Author(s):  
Marco Herrera ◽  
Jeonghwan Kim ◽  
Yulia Eygeris ◽  
Antony Jozic ◽  
Gaurav Sahay
Keyword(s):  
Lipid Nanoparticles ◽  
Endosomal Escape

Galectin8-GFP cytosolic redistribution to bright puncta serve as sensor for LNP escape from endosomal compartments.

scholarly journals RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen-Chen Huang ◽  
Fang-Rui Liu ◽  
Qiang Feng ◽  
Xin-Yan Pan ◽  
Shu-Ling Song ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Membrane ◽  
Fusion Protein ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fusion Proteins ◽  
Inhibitory Effect ◽  
Endosomal Escape ◽  
Antitumor Effects ◽  
Sw480 Cells

Abstract Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

Core Role of Hydrophobic Core of Polymeric Nanomicelle in Endosomal Escape of siRNA

Nano Letters ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 3680-3689
Author(s):  
Chunhui Li ◽  
Junhui Zhou ◽  
Yidi Wu ◽  
Yanliang Dong ◽  
Lili Du ◽  
...  
Keyword(s):  
Endosomal Escape ◽  
Hydrophobic Core ◽  
Core Role

scholarly journals Novel PEGylated Lipid Nanoparticles Have a High Encapsulation Efficiency and Effectively Deliver MRTF-B siRNA in Conjunctival Fibroblasts

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 382
Author(s):  
Amisha Sanghani ◽  
Konstantinos N. Kafetzis ◽  
Yusuke Sato ◽  
Salsabil Elboraie ◽  
Julia Fajardo-Sanchez ◽  
...  
Keyword(s):  
Encapsulation Efficiency ◽  
Serum Response Factor ◽  
Cationic Lipid ◽  
Endosomal Escape ◽  
The Novel ◽  
Small Interfering Rnas ◽  
Glaucoma Filtration Surgery ◽  
Promising Therapeutic Approach ◽  
Cleavable Peptide

The master regulator of the fibrosis cascade is the myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway, making it a key target for anti-fibrotic therapeutics. In the past, inhibitors and small interfering RNAs (siRNAs) targeting the MRTF-B gene have been deployed to counter fibrosis in the eye, with the latter showing promising results. However, the biggest challenge in implementing siRNA therapeutics is the method of delivery. In this study, we utilised the novel, pH-sensitive, cationic lipid CL4H6, which has previously demonstrated potent targeting of hepatocytes and endosomal escape, to safely and efficiently deliver an MRTF-B siRNA into human conjunctival fibroblasts. We prepared two lipid nanoparticle (LNP) formulations, incorporating targeting cleavable peptide cY in one of them, and measured their physicochemical properties and silencing effect in human conjunctival fibroblasts. Both proved to be non-cytotoxic at a concentration of 50 nM and effectively silenced the MRTF-B gene in vitro, with the targeting cleavable peptide not affecting the silencing efficiency [LNP with cY: 62.1% and 81.5% versus LNP without cY: 77.7% and 80.2%, at siRNA concentrations of 50 nM (p = 0.06) and 100 nM (p = 0.09), respectively]. On the other hand, the addition of the targeting cleavable peptide significantly increased the encapsulation efficiency of the LNPs from 92.5% to 99.3% (p = 0.0005). In a 3D fibroblast-populated collagen matrix model, both LNP formulations significantly decreased fibroblast contraction after a single transfection. We conclude that the novel PEGylated CL4H6-MRTF-B siRNA-loaded LNPs represent a promising therapeutic approach to prevent conjunctival fibrosis after glaucoma filtration surgery.

Peptide-nucleic acid nanostructures for transfection

2012 ◽  
Vol 3 (3) ◽  
pp. 283-293 ◽  
Author(s):  
Burkhard Bechinger
Keyword(s):  
Nucleic Acid ◽  
Physicochemical Properties ◽  
Cellular Uptake ◽  
Peptide Nucleic Acid ◽  
Endosomal Escape ◽  
Medical Applications ◽  
Specific Cell ◽  
Charge Composition ◽  
Cell Surfaces ◽  
Intracellular Targeting

AbstractTo use nucleic acids in biomedical research and medical applications, these highly hydrophilic macromolecules have to be transported through the organism, targeted to specific cell surfaces, and have to cross cellular barriers. To this end, nanosized transfection complexes have been designed and several of them have been successfully tested. Here, the different steps of the transfection process and the particular optimization protocols are reviewed, including the physicochemical properties of such vectors (size, charge, composition), protection in serum, cellular uptake, endosomal escape, and intracellular targeting. The transfection process has been subdivided into separate steps and here special emphasis is given to peptides that have been designed to optimize these steps individually. Finally, complex devices encompassing a multitude of beneficial functionalities for transfection have been developed.

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