Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

Abstract

Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells.

Hybrids of Iron-Filled Multiwall Carbon Nanotubes and Anticancer Agents as Potential Magnetic Drug Delivery Systems: In Vitro Studies against Human Melanoma, Colon Carcinoma, and Colon Adenocarcinoma

“…It was found that "drug-nanotube" hybrids landed, pierced, or in a few cases penetrated cancer cells, similar to our previous studies [42], and the fluorescent drugs were unloaded intracellularly, mainly by diffusion after enzymatic cleavage or physical unloading. The enhanced cell penetration by nanotubes, also in the presence of magnetic field and noncytotoxic to human monocyte macrophage cells, was described by Boncel et al [42] and Mahmood et al [55]. The latter complex mechanism opens an additional route of intracellular release in the presence of a magnetic field.…”

Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation

“…In addition to facilitate a passive targeting, various studies have demonstrated that carbon nanomaterials can also act as anti-tumor agents themselves and sensitize cancer cells to cytotoxic drugs such as etoposide [23–24 26], dexamethasone [23], paclitaxel [25] and CDDP [16]. In accordance, we have previously shown that CNFs and multiwalled CNTs could enhance the anti-proliferative and pro-apoptotic effects of CDDP and CP in prostate and bladder cancer cells [27].…”

“…However, synergistic increases of the expected effects of 1.3-, 1.4- and 1.6-fold could be observed for the combinations CNFs–DTX (cell colony formation), CNFs–MMC (cell death rate) and CNFs–CP (cell death rate), respectively (Table 3). Furthermore, other studies have also demonstrated that single-walled CNTs can augment the effectiveness of cytotoxic drugs such as etoposide and paclitaxel via enhanced apoptosis [24–26]. The single-walled CNTs have been applied in concentrations of up to 20 µg/mL in these studies [24–26], whereupon one has to bear in mind that single-walled CNTs are more toxic than multiwalled CNTs [33].…”

“…Carbon nanomaterials can also augment the cell-damaging effects of conventional chemotherapeutics and cytotoxic agents by chemosensitizing cancer cells [16,23–26]. In our previous studies, CNTs and CNFs sensitized prostate and bladder cancer cells to the platinum-based chemotherapeutics carboplatin (CP) and cisplatin (CDDP) via an enhanced inhibition of short- and long-term proliferation as well as by an increased induction of apoptosis [27–28].…”

Plasmonic nanoparticles and their characterization in physiological fluids

“…In a similarly pioneering study, Huang et al used DFM to show the preferential binding of Au nanospheres and nanorods to cancer cells over healthy cells after functionalization of the NPs with a targeting moiety [85]. Both these studies, among others [107], have applied DFM mostly as a qualitative technique to confirm the presence, and approximate abundance, of the NP of interest. However, as is often the case with microscopy, extracting quantitative characterization data about the state of NPs in biological fluids can be challenging.…”