Mapping mechanical properties of living cells at nanoscale using intrinsic nanopipette–sample force interactions

Колмогоров, Василий; Erofeev, Alexander; Woodcock, Emily; Efremov, Yuri M.; Iakovlev, Aleksei; Savin, Nikita; Alova, A.; Lavrushkina, Svetlana; Kireev, Igor I.; Prelovskaya, A.O.; Sviderskaya, Elena V.; Scaini, Denis; Klyachko, Natalia L.; Timashev, Peter; Takahashi, Yasufumi; Salikhov, S. V.; Parkhomenko, Yu. N.; Majouga, Alexander G.; Edwards, C. R. W.; Novák, Pavel; Korchev, Yuri; Gorelkin, Petr

doi:10.1039/d0nr08349f

Cited by 50 publications

(51 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Topography and a Young's modulus analysis were performed, as was recently described, by scanning ion conductance microscopy (SICM) for quantitative nanomechanical mapping (QNM). 47 In this case we analyzed the changes in the cytoskeleton, which were induced by substances that affected the microtubules, by analyzing the mechanical properties of the living cell over the incubation time with MMAE and PSMA-Val-Cit-PAB-MMAE at corresponding Also, the same QNM measurement was performed on the control 22Rv1 cells without any drug treatment. The MMAE mechanism of action is based on tubulin binding, resulting in microtubule destabilization.…”

Section: 3mentioning

confidence: 99%

“…24 Also among the promising radiopharmaceuticals is a recently proposed analog of PSMA-617, a PSMA-D4 conjugate where the 2-naphthylalanine fragment is replaced by tryptophan. This conjugate is capable of chelating the isotopes 90 Y, 47 Sc, 68 Ga, and 177 Lu. 25 Its derivative PSMA-T4, where a fragment of DOTA is replaced with a fragment of HYNIC, is also known to bind 99m Tc isotopes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate

et al. 2021

Self Cite

View full text Add to dashboard Cite

Prostate cancer is the second most common type of cancer among men. Its main method of treatment is chemotherapy, which has a wide range of side effects. One of the solutions to this challenge is targeted delivery to prostate cancer cells. Here we synthesized a novel small-molecule PSMA-targeted conjugate based on the monomethyl auristatin E. Its structure and conformational properties were investigated by NMR spectroscopy. Cytotoxicity, intracellular reactive oxygen species induction, and stability under liver microsomes and P450-cytochrome species were investigated for this conjugate. The conjugate demonstrated 77–85% tumor growth inhibition levels on 22Rv1 (PSMA (+)) xenografts, compared with a 37% inhibition level on PC-3 (PSMA (−)) xenografts, in a single dose of 0.3 mg/kg and a sufficiently high therapeutic index of 21. Acute, chronic, and subchronic toxicities and pharmacokinetics have shown that the synthesized conjugate is a promising potential agent for the chemotherapy of prostate cancer.

show abstract

Section: 3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…SICM is a non-contact type of scanning probe microscopy applicable for the investigation of live biological samples in liquid [ 78 , 79 , 80 , 81 ]. This method was used to study the influence of antifungal thiazolidines on the topography of living Candida cells.…”

Section: Resultsmentioning

confidence: 99%

“…The nanopipette radius ranged from 20 to 35 nm to achieve a nanoscale resolution of topography imaging. The radius of the nanopipette and the mechanical characteristics were calculated using formulas reported in previous studies [ 80 ]. Cell images were recorded on areas of 10 × 10 µm at 74 nm resolution and on areas of 1.5 × 1.5 µm for 21 nm resolution.…”

Section: Methodsmentioning

confidence: 99%

Antifungal Thiazolidines: Synthesis and Biological Evaluation of Mycosidine Congeners

et al. 2022

Self Cite

View full text Add to dashboard Cite

Novel derivatives of Mycosidine (3,5-substituted thiazolidine-2,4-diones) are synthesized by Knoevenagel condensation and reactions of thiazolidines with chloroformates or halo-acetic acid esters. Furthermore, 5-Arylidene-2,4-thiazolidinediones and their 2-thioxo analogs containing halogen and hydroxy groups or di(benzyloxy) substituents in 5-benzylidene moiety are tested for antifungal activity in vitro. Some of the synthesized compounds exhibit high antifungal activity, both fungistatic and fungicidal, and lead to morphological changes in the Candida yeast cell wall. Based on the use of limited proteomic screening and toxicity analysis in mutants, we show that Mycosidine activity is associated with glucose transport. This suggests that this first-in-class antifungal drug has a novel mechanism of action that deserves further study.

show abstract

“…Nanopipettes have emerged as a promising platform in recent years since they have found many applications in analytical chemistry and can be easily fabricated. [23][24][25] Nanopipettes are used for imaging of biological objects with scanning ion-conductance microscopy, 26 quantitative nanomechanical mapping of cells, 27 dynamic mapping of extracellular pH at the singlecell level, 28 detection of protein 29 and determination of ROS generation under the influence of novel prospective antitumor drugs. [30][31][32][33][34] Recently, disk-shaped carbon nanoelectrodes (CNEs) have been used to determine reactive oxygen/nitrogen species (ROS / RNS), 23,[35][36][37][38][39][40][41] oxygen, 23 ATP, 42 and catecholamines 43 inside single cells.…”

mentioning

confidence: 99%

In vitro/ In vivo Electrochemical Detection of Pt(II) Species

Vaneev

Gorelkin

Krasnovskaya

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

The biodistribution of chemotherapy compounds within tumor tissue is one of the main challenges in the development of antineoplastic drugs, and novel techniques for simple, non-expensive, sensitive, and selective detection of various analytes in tumors are of great importance. In this paper we propose the use of platinized carbon nanoelectrodes (PtNE) for electrochemical detection of platinum-based drugs in various biological models, including single cells and tumor spheroids in vitro, and inside solid tumors in vivo. We have demonstrated quantitative direct detection of Pt(II) in breast adenocarcinoma MCF-7 cells treated with cisplatin and cisplatin-based DNP prodrug. To realize the potential of this technique in advanced tumor models, we measured Pt(II) in 3D tumor spheroids in vitro and tumor-bearing mice in vivo. The concentration gradient of Pt (II) species correlated with the distance from the sample surface in MCF-7 tumor spheroids. We then performed detection of Pt(II) species in tumor-bearing mice treated intravenously with cisplatin and DNP. We found that there was deeper penetration of DNP in comparison to cisplatin. This research demonstrates a novel minimally invasive, real-time electrochemical technique for the study of platinum-based drugs.

show abstract

Mapping mechanical properties of living cells at nanoscale using intrinsic nanopipette–sample force interactions

Abstract: Mechanical properties of living cells determined by cytoskeletal elements play a crucial role in a wide range of biological functions. However, low-stress mapping of mechanical properties with nanoscale resolution but...

Cited by 50 publications

References 42 publications

Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate

Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate

Antifungal Thiazolidines: Synthesis and Biological Evaluation of Mycosidine Congeners

In vitro/ In vivo Electrochemical Detection of Pt(II) Species

Contact Info

Product

Resources

About