The great escape: how cationic polyplexes overcome the endosomal barrier

Buś, Tanja; Traeger, Anja; Schubert, Ulrich S.

doi:10.1039/c8tb00967h

Cited by 313 publications

(306 citation statements)

References 205 publications

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“…on the cell surface (Harush-Frenkel et al, 2007). After attachment to the plasma membrane, enter the cells by means of clathrin-mediated endocytosis, caveolaemediated endocytosis and macropinocytosis (Bus et al, 2018). Moreover, nanoparticles can also be mediated via endocytosis or vesicles across cell membranes without the need for any specific receptors, suggesting that nanoparticle traverse the cell membranes can be driven by general physicochemical interactions (Contini et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer

et al. 2019

Drug Delivery

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2020) Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer, Drug Delivery, 27:1, 100-109, ABSTRACT Purpose: Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles (ZNPs) to achieve tumor targeting and reduce toxic side effects of DM1. Methods: ZNPs were prepared by phase separation and Box-Behnken design was used to optimize the formulation. Then, confocal fluorescence microscope and flow cytometry were used to determine cellular uptake of ZNPs. A549 cells were cultured in vitro to study cytotoxicity and used to establish tumor xenografts in nude mice. Biodistribution and antitumor activity of ZNPs were performed in vivo experiments. In addition, we also performed histological and immunohistochemical examinations on tumors and viscera. Results: The optimal prescription was obtained by using 120 lL zein added to 2 mL water under stirring in 300 rpm. The encapsulation efficiency and drug loading were 82.97 ± 0.80% and 3.32 ± 0.03%, respectively. We found that DM1-loaded ZNPs have a strong inhibitory effect on A549 cells, which stemmed from the ability of ZNPs to enhance cellular uptake. Furthermore, we demonstrated that DM1-loaded ZNPs exhibits a better antitumor efficacy than DM1, which tumor inhibition rate were 97.3% and 92.7%, respectively. The biodistribution revealed that ZNPs could targeted to tumor. Finally, we confirmed by histological that DM1-loaded ZNPs are nontoxic. Conclusion: DM1-loaded ZNPs have considerable antitumor activity. Thus, DM1-loaded ZNPs are a promising treatment of non-small cell lung cancer. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer

et al. 2019

Drug Delivery

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“…While the proton sponge mechanism of PEI is still under debate, its endosomal escape phenomenon has been replicated numerous times, and has been extensively used to demonstrate effective in vivo gene silencing effect in numerous nanosystems, as shown in Table . More recently, alternative models to explain polyplex‐mediated endosomal membrane disruption have been proposed and are under investigation …”

Section: Strategies Against Endocytosismentioning

confidence: 99%

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201903637.With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.

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“…139 One characteristic of PEI is that its protonation and charge density increase at low pH, which protects the nucleic acids from nuclease degradation and promotes endosomal escape at acidifying endosomes. 140,141 The most widely used PEI polymers are 22-kDa linear PEI (L-PEI) and 25-kDa branched PEI (B-PEI), both of which have moderate cytotoxicity. 142 Recently, an optimized PEI and its derivatives have been used in mRNA delivery.…”

Section: Reviewmentioning

confidence: 99%

Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9

2019

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Genome-editing technologies based on programmable nucleases have significantly broadened our ability to make precise and direct changes in the genomic DNA of various species, including human cells. Delivery of programmable nucleases into the target tissue or cell is one of the pressing challenges in transforming the technology into medicine. In vitro-transcribed (IVT) mRNA-mediated delivery of nucleases has several advantages, such as transient expression with efficient in vivo and in vitro delivery, no genomic integration, a potentially low off-target rate, and high editing efficiency. This review focuses on key barriers related to IVT mRNA delivery, on developed modes of delivery, and on the application and future prospects of mRNA encoding nuclease-mediated genome editing in research and clinical trials. Principles of Genome Editing Genome-Editing Nucleases CRISPR-Cas systems are essentially RNA-guided nucleases. Unlike the aforementioned nucleases that recognize the target sequence

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The great escape: how cationic polyplexes overcome the endosomal barrier

Abstract: Endo-lysosomal escape strategies of cationic polymer-mediated gene delivery at a glance.

Cited by 313 publications

References 205 publications

Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer

Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9

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