Carbon nanohorns as nanocontainers for cisplatin: insight into their interaction with the plasma membranes of normal and breast cancer cells

Almeida, Eduardo R.; Santos, Hélio F. Dos; Capriles, Priscila V. S. Z.

doi:10.1039/d1cp02015c

Cited by 6 publications

(27 citation statements)

References 67 publications

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“…This behavior reflects a reduction in the number of interactions between the drugs and the nanocarrier in the adsorbed formulations. Moreover, the drug–CNHox pair energies are mainly composed of vdw interactions, as we also concluded for the 3cddp@CNHox complex . Recently, Mejri et al reported a pair energy value of −80.0 kcal mol –1 for an inclusion complex formed by four cddp molecules encapsulated into a hydroxyl-terminated CNT (4cddp@CNT in our notation).…”

Section: Resultssupporting

confidence: 81%

“…Overall, the negative values of the free energies shown in Table indicate that the CNHox model forms stable complexes with cddp, as we recently reported it, and cpx and oxa. This behavior is also graphically represented by the green bars in Figure .…”

Section: Resultssupporting

confidence: 68%

“…In this figure, the peaks between 0 and 5 Å point out the presence of inner solvation shells (waters inside the cavity). We also reported in our last papers complexes including pristine and oxidized and reduced CNH prototypes. − Regarding the inclusion complexes (Figure S8A), while the RDF referring to cddp@CNHox and cpx@CNHox complexes present three peaks centered at 0.45, 2.85, and 3.75 Å and 0.15, 2.85, and 3.75 Å, respectively, the oxa@CNHox complex presents only two peaks centered at 2.85 and 4.35 Å. The smallest number of peaks in the g ( r ) CM–O w of the oxa@CNHox model associated with the distance of its first peak suggests that the volume occupied by the oxa molecule in the cavity of the CNHox reduced the access of solvent molecules.…”

Section: Resultsmentioning

confidence: 68%

“…Regarding the CNH structure, we employed the same oxidized topology (C 280 H 54 O 41 ) reported in our last paper with average length and diameter of 27.4 and 9.0 Å, respectively. In brief, this model, henceforth termed CNHox, has hydroxyl, carbonyl, and carboxyl groups on its surface due to the oxidation mechanism with O 2 and H 2 O. , In addition to the presence of hydroxyls at the open end, this prototype includes a nanowindow with an average diameter of 11 Å on its surface, which agrees with the experimental data from this oxidation process .…”

Section: Methodsmentioning

confidence: 99%

“…About the Pt(II)-based drugs, we employed the conventional parameterization procedure described in our last papers. − In this scheme, the intramolecular parameters were calculated from the optimized structures at the MP2/6-31G(d,p)/LANL2DZ level of theory. The force constants for bonds and angles were derived using the Visual Force Field Toolkit .…”

Section: Methodsmentioning

confidence: 99%

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Unveiling the Releasing Processes of Pt(II)-Based Anticancer Drugs from Oxidized Carbon Nanohorn: An In Silico Study

2022

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About half of all cancer chemotherapies currently applied involve medication with the three worldwide approved Pt(II)-based drugs, cisplatin (cddp), carboplatin (cpx), and oxaliplatin (oxa), due to their notable antitumor activity for several cancers. However, this wide application is accompanied by severe side effects, such as nephrotoxicity, myelosuppression, and neurotoxicity, as a result of their low bioavailability and selectivity for cancer cells. To mitigate these drawbacks, the use of chemically functionalized carbon nanohorns (CNH) as nanocarriers represents a potential formulation since CNH has been noted for their biodegradability, biocompatibility, low toxicity, and cavities dimensionally compatible with small drugs. This work reports energetic and dynamic analyses of complexes formed by oxidized CNH (CNHox) and the cddp, cpx, and oxa drugs. Using unbiased molecular dynamics (MD) simulations, we show that the encapsulated formulations (cddp@CNHox, cpx@CNHox, and oxa@CNHox) were more stable by ∼11.0 kcal mol–1 than the adsorbed ones (cddp > CNHox, cpx > CNHox, and oxa > CNHox). This high stability, mainly governed by van der Waals interactions, was responsible for the drug confinement during the entire simulation time (200 ns). The biased MD simulations of the inclusion complexes confirmed the nonspontaneity of the drug release since the potentials of mean force (PMF) indicated the endergonic character of this process. Additionally, the releasing energy profiles pointed out that the free energy barrier (ΔΔG ≠) for the escape from CNHox cavity follows the order oxa > cpx ∼ cddp, with the value for the oxa complex (21–26 kcal mol–1) found to be about 36 and 30% larger than those for cpx and cddp, respectively. While the approximate residence time (t res) of the oxa drug inside the CNHox cavity was 5.45 × 108 s, the same measure for the cddp and cpx drugs was 5.3 × 105 and 1.60 × 103 s. Simulations also revealed that the escape of oxa with the oxalate group facing the nanowindow was the most unfavorable process, giving t res = 1.09 × 109 s. Besides reinforcing and extending the nanovectorization of cddp, cpx, and oxa in CNHox for cancer chemotherapies, all features considered may provide interpretations for experimental data and encourage new investigations aiming to propose less aggressive treatments for oncological diseases.

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Section: Resultssupporting

confidence: 81%

Section: Resultssupporting

confidence: 68%