Enhanced cellular uptake of platinum by a tetracationic Pt(II) nanocapsule and its implications to cancer treatment

Ahmedova, Anife; Mihaylova, Rositsa; Stoykova, Silviya; Mihaylova, Veronika; Paunova-Krasteva, Tsvetelina; Mihaylov, Lyuben; Stoitsova, Stoyanka; Nihtianova, D.; Momekov, Georgi; Momekova, Denitsa; Yoshizawa, Michito

doi:10.1016/j.ejps.2020.105545

Cited by 5 publications

(6 citation statements)

References 53 publications

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“…For the application of NDDSs, since therapeutics must be taken up by tumor cells to achieve therapeutic efficacy of cancer treatment, cellular uptake profile reflects the delivery efficiency and the bioavailability of nanocarriers [ 23 – 25 ]. Among various physicochemical properties of NDDSs, one of dominant factors is the surface charge which control various biological responses to delivery systems.…”

Section: Effect Of Surface Charge On the Uptake Of Nanocarriersmentioning

confidence: 99%

Charge reversal nano-systems for tumor therapy

Zhang

Chen

et al. 2022

J Nanobiotechnol

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Surface charge of biological and medical nanocarriers has been demonstrated to play an important role in cellular uptake. Owing to the unique physicochemical properties, charge-reversal delivery strategy has rapidly developed as a promising approach for drug delivery application, especially for cancer treatment. Charge-reversal nanocarriers are neutral/negatively charged at physiological conditions while could be triggered to positively charged by specific stimuli (i.e., pH, redox, ROS, enzyme, light or temperature) to achieve the prolonged blood circulation and enhanced tumor cellular uptake, thus to potentiate the antitumor effects of delivered therapeutic agents. In this review, we comprehensively summarized the recent advances of charge-reversal nanocarriers, including: (i) the effect of surface charge on cellular uptake; (ii) charge-conversion mechanisms responding to several specific stimuli; (iii) relation between the chemical structure and charge reversal activity; and (iv) polymeric materials that are commonly applied in the charge-reversal delivery systems. Graphical Abstract

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Section: Effect Of Surface Charge On the Uptake Of Nanocarriersmentioning

confidence: 99%

Charge reversal nano-systems for tumor therapy

Zhang

Chen

et al. 2022

J Nanobiotechnol

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“…Others have examined DNA binding and nuclease activity ( Childs et al, 2006 ), and the cytotoxicity of related double-stranded complexes ( Holtze et al, 2006 ; Allison et al, 2018 ). In addition, quadruple-stranded helicates have been shown to be cytotoxic ( Mcneill et al, 2015 ; Ahmedova et al, 2016a ; Ahmedova et al, 2016b ; Schmidt et al, 2016 ; Vasdev et al, 2018 ; Ahmedova et al, 2020 ) and in some cases the modes of action of the complexes have been studied ( Mcneill et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Cavity-Containing [Fe2L3]4+ Helicates: An Examination of Host-Guest Chemistry and Cytotoxicity

et al. 2021

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Two new di(2,2′-bipyridine) ligands, 2,6-bis([2,2′-bipyridin]-5-ylethynyl)pyridine (L1) and bis(4-([2,2′-bipyridin]-5-ylethynyl)phenyl)methane (L2) were synthesized and used to generate two metallosupramolecular [Fe2(L)3](BF4)4 cylinders. The ligands and cylinders were characterized using elemental analysis, electrospray ionization mass spectrometry, UV-vis, 1H-, 13C and DOSY nuclear magnetic resonance (NMR) spectroscopies. The molecular structures of the [Fe2(L)3](BF4)4 cylinders were confirmed using X-ray crystallography. Both the [Fe2(L1)3](BF4)4 and [Fe2(L2)3](BF4)4 complexes crystallized as racemic (rac) mixtures of the ΔΔ (P) and ΛΛ (M) helicates. However, 1H NMR spectra showed that in solution the larger [Fe2(L2)3](BF4)4 was a mixture of the rac-ΔΔ/ΛΛ and meso-ΔΛ isomers. The host-guest chemistry of the helicates, which both feature a central cavity, was examined with several small drug molecules. However, none of the potential guests were found to bind within the helicates. In vitro cytotoxicity assays demonstrated that both helicates were active against four cancer cell lines. The smaller [Fe2(L1)3](BF4)4 system displayed low μM activity against the HCT116 (IC50 = 7.1 ± 0.5 μM) and NCI-H460 (IC50 = 4.9 ± 0.4 μM) cancer cells. While the antiproliferative effects against all the cell lines examined were less than the well-known anticancer drug cisplatin, their modes of action would be expected to be very different.

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“…After 24 h of incubation, cells were treated with 2-fold serial dilutions of the compounds in the appropriate concentration range according to their chemosensitivity profiles. Treated cells were incubated for 72 h and were further processed according to the protocol described earlier [ 33 , 34 , 35 ]. A nonlinear regression analysis was applied for the estimation of the IC 50 values from the concentration–response curves and using the curve fit (GraphPad Prizm 8.01 Software).…”

Section: Methodsmentioning

confidence: 99%

“…The mass spectrometer was optimized to ensure the maximum intensity of the Pt isotopes. The instrumental conditions for ICP-MS were described in [ 35 ]. The concentration of platinum in the analyzed samples was measured by the following isotopes: 192 Pt, 194 Pt, 195 Pt, 196 Pt, and 198 Pt.…”

Section: Methodsmentioning

confidence: 99%

“…Correlations were sought between the cytotoxicity of 1 and 2 and their chemical reactivity, as well as internalization in the cancer cells that was performed on two types of cells: adherent and suspension, for the sake of comparison. The latter was estimated by ICP-MS both in whole cells and in different cell fractions by using procedures from our previous studies on the mentioned metallosupramolecular capsules [ 35 ]. Moreover, a proteome analysis on HL-60 leukemia cells was performed in an attempt to identify the molecular pathways affected by the studied pyrenebutyrate Pt(IV) complexes.…”

Section: Introductionmentioning

confidence: 99%

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Pyrenebutyrate Pt(IV) Complexes with Nanomolar Anticancer Activity

Ahmedova,

Mihaylova,

Stoykova

et al. 2023

Pharmaceutics

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Research on platinum-based anticancer drugs continuously strives to develop new non-classical platinum complexes. Pt(IV) prodrugs are the most promising, and their activation-by-reduction mechanism of action is being explored as a prospect for higher selectivity and efficiency. Herein, we present the anticancer potency and chemical reactivity of Pt(IV) complexes formed by linking pyrene butyric acid with cisplatin. The results from cytotoxicity screening on 10 types of cancer cell lines and non-malignant cells (HEK-293) indicated IC50 values as low as 50–70 nM for the monosubstituted Pt(IV) complex against leukemia cell lines (HL-60 and SKW3) and a cisplatin-resistant derivative (HL-60/CDDP). Interestingly, the bis-substituted complex is virtually non-toxic to both healthy and cancerous cells of adherent types. Nevertheless, it shows high cytotoxicity against multidrug-resistant derivatives HL-60/CDDP and HL-60/Dox. The reactivity of the complexes with biological reductants was monitored by the NMR method. Furthermore, the platinum uptake by the treated cells was examined on two types of cellular cultures: adherent and suspension growing, and proteome profiling was conducted to track expression changes of key apoptosis-related proteins in HL-60 cells. The general conclusion points to a possible cytoskeletal entrapment of the bulkier bis-pyrene complex that could be limiting its cytotoxicity to adherent cells, both cancerous and healthy ones.

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Enhanced cellular uptake of platinum by a tetracationic Pt(II) nanocapsule and its implications to cancer treatment

Cited by 5 publications

References 53 publications

Charge reversal nano-systems for tumor therapy

Charge reversal nano-systems for tumor therapy

Cavity-Containing [Fe2L3]4+ Helicates: An Examination of Host-Guest Chemistry and Cytotoxicity

Pyrenebutyrate Pt(IV) Complexes with Nanomolar Anticancer Activity

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