A pH-sensitive fluorescent protein sensor to follow the pathway of calcium phosphate nanoparticles into cells

Kollenda, Sebastian; Kopp, Mathis; Wens, Jasmin; Koch, Johannes; Schulze, Nina; Papadopoulos, Chrisovalantis; Pöhler, Robert; Meyer, Hemmo; Epple, Matthias

doi:10.1016/j.actbio.2020.05.014

Cited by 29 publications

(14 citation statements)

References 91 publications

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“…They are typically taken up via endocytosis into endosomes which convert to endolysosomes. [ 22 ] The acidic pH in endolysosomes leads to the dissolution of calcium phosphate and the release of the (bio)molecular cargo. It is assumed that an increase of the endolysosomal osmotic pressure due to the ion release from calcium phosphate leads to the rupture of the endolysosome before the cargo has been degraded (endosomal escape), [ 23 ] similarly as with the polyelectrolyte poly(ethyleneimine), PEI (proton sponge effect).…”

Section: Resultsmentioning

confidence: 99%

Suppositories with bioactive calcium phosphate nanoparticles for intestinal transfection and gene silencing

Hosseini

Epple

2020

Nano Select

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Calcium phosphate nanoparticles (diameter about 60 nm, triple‐shell) were loaded with nucleic acids (DNA or siRNA) for local gene therapy in the colon. To avoid the oral administration where a passage through the stomach is necessary, the nanoparticles were incorporated into custom‐made hard‐fat suppositories after freeze‐drying with trehalose. After melting the suppository at 37°C, the nanoparticles were released and well dispersed in cell culture medium. They retained their bioactivity as shown by in vitro cell culture studies with the model cell line HeLa and the colon cancer cell line Caco‐2. The nanoparticles were easily taken up by both cell types and also efficient for transfection and gene silencing, as shown with the model protein eGFP. This opens a way for local gene therapy in the colon.

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Section: Resultsmentioning

confidence: 99%

Suppositories with bioactive calcium phosphate nanoparticles for intestinal transfection and gene silencing

Hosseini

Epple

2020

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“…Time-lapse confocal microscopy confirmed that the Ta ndem-loaded nanoparticles were directed to endolysosomes after endocytic uptake. [73] The uptake of calcium phosphate nanoparticles hasa lso been studied in 3D cell culture models on spheroids generated from HeLa cellsw ith ad iametera round5 00 mm. The distribution of red fluorescent calcium phosphate nanoparticles inside the spheroids was visualized by confocal laser scanning microscopy.I twasa lso shown on the cellular level that nanoparticles were taken up by single cells inside as pheroid (Figure 7).…”

Section: Uptake Of Calcium Phosphate Nanoparticles By Cells In Vitromentioning

confidence: 99%

Biological and Medical Applications of Calcium Phosphate Nanoparticles

Sokolova

Epple

2021

Chemistry A European J

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Calcium phosphate nanoparticles have ah igh biocompatibility and biodegradability due to their chemical similarity to human hard tissue, for example, bone and teeth. They can be used as efficient carriers for different kinds of biomolecules such as nucleic acids, proteins, peptides, antibodies, or drugs,w hich alone are not able to enter cells where their biological effect is required. They can be loaded with cargom olecules by incorporating them, unlike solid nanoparticles, and also by surface functionalization.This offersp rotection,f or example, against nucleases,a nd the possibility forc ell targeting. If such nanoparticles are functionalized with fluorescing dyes, they can be appliedf or imagingi nv itro and in vivo. Synthesis, functionalization and cell uptake mechanismso fc alcium phosphate nanoparticles are discussed together with applications in transfection, gene silencing, imaging, immunization, and bone substitution. Biodistribution data of calcium phosphate nanoparticles in vivo are reviewed.

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“…[ 21 ] Nanoparticles (NPs) can enter target cells through a variety of mechanisms. The nanoparticles are first absorbed into vesicles and enter the early endosome (pH drops to ≈6.3), and then are recovered to the cytoplasm or transported to the late endosome (pH 5.5), [ 22 ] and the contents are further transported to the lysosomes (pH 4.7), [ 23 ] in which they are degraded by acid hydrolases. Taking advantage of this gradual increase in acidity during the uptake process, acid‐labile nanomaterials have been proven to be the most promising system for evading the mildly acidic endosomal/lysosomal compartment (pH 4–5) and exert its efficacy.…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin‐Derived ROS‐Generating Nanomedicine with pH‐Modulated Degradability to Enhance Tumor Ferroptosis Therapy and Chemotherapy

Zha

Han

et al. 2022

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Nowadays, destruction of redox homeostasis to induce cancer cell death is an emerging anti‐cancer strategy. Here, the authors utilized pH‐sensitive acetalated β‐cyclodextrin (Ac‐β‐CD) to efficiently deliver dihydroartemisinin (DHA) for tumor ferroptosis therapy and chemodynamic therapy in a synergistic manner. The Ac‐β‐CD‐DHA based nanoparticles are coated by an iron‐containing polyphenol network. In response to the tumor microenvironment, Fe2+/Fe3+ can consume glutathione (GSH) and trigger the Fenton reaction in the presence of hydrogen peroxide (H2O2), leading to the generation of lethal reactive oxygen species (ROS). Meanwhile, the OO bridge bonds of DHA are also disintegrated to enable ferroptosis of cancer cells. Their results demonstrate that these nanoparticles acted as a ROS generator to break the redox balance of cancer cells, showing an effective anticancer efficacy, which is different from traditional approaches.

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A pH-sensitive fluorescent protein sensor to follow the pathway of calcium phosphate nanoparticles into cells

Cited by 29 publications

References 91 publications

Suppositories with bioactive calcium phosphate nanoparticles for intestinal transfection and gene silencing

Suppositories with bioactive calcium phosphate nanoparticles for intestinal transfection and gene silencing

Biological and Medical Applications of Calcium Phosphate Nanoparticles

Cyclodextrin‐Derived ROS‐Generating Nanomedicine with pH‐Modulated Degradability to Enhance Tumor Ferroptosis Therapy and Chemotherapy

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