Confinement of the antitumoral drug cisplatin inside edge-functionalized carbon nanotubes and its release near lipid membrane

Méjri, Alia; Tangour, Bahoueddine; Herlem, Guillaume; Picaud, Fabien

doi:10.1140/epjd/s10053-021-00114-7

Cited by 4 publications

(8 citation statements)

References 79 publications

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“…Moreover, the drug−CNHox pair energies are mainly composed of vdw interactions, as we also concluded for the 3cddp@CNHox complex. 43 Recently, Mejri et al 48 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). In that work, if we consider the value of −20.0 kcal mol −1 for the case of a complex loaded with only one cddp molecule (cddp@CNT in our notation), we could state that the interaction energy for cddp@CNHox is 3.8 times lower (more negative) than the one reported by these authors.…”

Section: Resultsmentioning

confidence: 88%

“…However, this confinement effect, which may be explained by the notable stability demonstrated in the free energy calculations (see Table ), suggests that the drug release process involves high energy barriers, especially if one considers the inclusion complexes. In fact, studies involving MD simulations of similar systems described the existence of energetic barriers for the cddp release from CNT. , …”

Section: Resultsmentioning

confidence: 99%

“…In fact, studies involving MD simulations of similar systems described the existence of energetic barriers for the cddp release from CNT. 44,48 3.2. Biased MD Simulations.…”

Section: Resultsmentioning

confidence: 99%

“…The notable difference of 40.19 kcal mol −1 in relation to the two complexes involving cddp presented herein (see Table 5) is probably an effect of the high steric hindrance of the nanowindow (diameter of ∼4.13Å) in the CNTox prototype, which made it difficult the diffusion of this Pt(II) drug (diameter of ∼7.75 Å) through this release pathway. In 2021, using a biased MD method (ABF method), Mejri and co-workers 48 reported an energy barrier of 3.3 kcal mol −1 , referring to the release of cddp along the main axis of a CNTox model. This small energetic barrier is probably connected not only with the size of the open end, which corresponds to the diameter of the CNTox model (13 Å) and also to the symmetry of the reaction coordinate that coincides perfectly with the longitudinal axis of the nanotube.…”

Section: Resultsmentioning

confidence: 99%

“…These biased methods are relevant since they provide a broad sampling of the phase space, including the high-energy states with significant probabilities, which would not be approached by unbiased simulations. 47 Recently, using the adaptative biasing force (ABF) method, Mejri et al 48 computed the free energy profiles for the cddp release from CNT models with carbon (CNT-C), hydrogen (CNT-H), and oxygen (CNT-OH) atoms at the edges of these tubes. The authors demonstrated that the energy barrier for the drug release from the CNT-C was 1.1 kcal mol −1 , whereas the barriers for the CNT-H and CNT-OH models were 2.3 and 3.3 kcal mol −1 .…”

Section: Introductionmentioning

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: Resultsmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

“…In fact, studies involving MD simulations of similar systems described the existence of energetic barriers for the cddp release from CNT. 44,48 3.2. Biased MD Simulations.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

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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Modeling the Cellular Uptake of Functionalized Carbon Nanohorns Loaded with Cisplatin through a Breast Cancer Cell Membrane

Almeida,

Goliatt,

Dos Santos

et al. 2023

Mol. Pharmaceutics

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The cisplatin encapsulation into carbon nanohorns (CNH) is a promising nanoformulation to circumvent the drug dissipation and to specifically accumulate it in tumor sites. Herein, biased molecular dynamics simulations were used to analyze the transmembrane transport of the CNH loaded with cisplatin through a breast cancer cell membrane prototype. The simulations revealed a four-stage mechanism: approach, insertion, permeation, and internalization. Despite the lowest structural disturbance of the membrane provided by the nanocarrier, the average free energy barrier for the translocation was 55.2 kcal mol −1 , suggesting that the passive process is kinetically unfavorable. In contrast, the free energy profiles revealed potential wells of −6.8 kcal mol −1 along the insertion stage in the polar heads region of the membrane, which might enhance the retention of the drug in tumor sites; therefore, the most likely cisplatin delivery mechanism should involve the adsorption and retention of CNH on the surface of cancer cells, allowing the loaded cisplatin be slowly released and passively transported through the cell membrane.

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Penetration of Chitosan into the Single Walled Armchair Carbon Nanotubes: Atomic Scale Insight

et al. 2021

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(1) Background: Currently, nanomaterials have been broadly used in various applications including engineering, medicine and biology. One of the carbon allotropes such as carbon nanotubes (CNTs) implemented for fabrication of nanocomposite materials due to the hypersensitivity. The combined design of nanomaterial with chitosan (CS) and CNT expands the field of exploitation from biosensing and tissue engineering to water desalination. Therefore, the penetration of CS into CNT provides a valuable insight into the interactions between CS and CNT. (2) Methods: We performed molecular dynamics simulations, applying the umbrella sampling method, in order to calculate the potential mean force between CS and CNT. (3) Results: The estimated penetration free energies showed that CS is favorable to the penetration into CNT cavities. However, the penetration nature differs depending on the CNT’s architecture. (4) Conclusions: Our finding revealed the CS penetration process into CNT with nanoscale precision. The investigation results assist in a better understanding of the nanocomposite materials based on CS-CNT.

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Confinement of the antitumoral drug cisplatin inside edge-functionalized carbon nanotubes and its release near lipid membrane

Cited by 4 publications

References 79 publications

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

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

Modeling the Cellular Uptake of Functionalized Carbon Nanohorns Loaded with Cisplatin through a Breast Cancer Cell Membrane

Penetration of Chitosan into the Single Walled Armchair Carbon Nanotubes: Atomic Scale Insight

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