In Vitro Targeting and Selective Killing of T47D Breast Cancer Cells by Purpurin and 5-Fluorouracil Anchored to Magnetic CNTs: Nitrene-Based Functionalization versus Uptake, Cytotoxicity, and Intracellular Fate

Abstract

Fe-encapsulated multiwall carbon nanotubes (Fe@MWCNTs) are candidates for magnetically targeted Drug Delivery Systems (mt-DDSs) against breast cancer. However, their full potential as versatile and biosafe vectors has yet to be developed. Key challenges that remain are relating surface functionalization to cytotoxicity and inducing selective cytotoxicity to cancer cells. We have studied quantitative uptake of pristine and functionalized Fe@MWCNTs (f-Fe@MWCNTs) in correlation to their in vitro cytotoxicity. Human monocyte macrophages (HMMs) and T47D breast cancer cells were selected as models to test selective cytotoxicity. [2+1]-Cycloaddition of nitrenes to Fe@MWCNTs yielded both effective functionalization and drug “tethering”. Hydrophilization of Fe@MWCNTs was critical for efficient active cell uptake. f-Fe@MWCNTs were considerably more toxic to T47D cells than HMMs, in spite of longer exposure times of the latter. Eventually, Fe@MWCNTs loaded with 5-fluorouracil in a β-cyclodextrin cage or with covalently linked purpurin emerged as the most cytotoxic and steerable in a magnetic field toward promising mt-DDSs.

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

“…The observations were possible because all of the hybrids exhibited fluorescence in the spectral range of 4 ,6-diamidino-2-phenylindole (DAPI). 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].…”

“…Nanotubes themselves, as vehicles enhancing targeting and revealing its intrinsic cytotoxicity, may be considered as potential platforms in the magnetic drug delivery. The earlier observed magnetic maneuverability [42] was here confirmed by Mössbauer spectroscopy which indicated the presence of Journal of Nanomaterials …”

“…In this work, extending our recent studies on in vitro magnetic targeting of breast cancer cells (T47D) with purpurinand 5FU-based Fe@MWCNT hybrids [42], we present anticancer activity and influence to selected cancer cells' life cycle of various covalent and noncovalent "drug-nanotube" hybrids based on Purp, 5FU, and 1,8-naphthalimide DNA intercalators (NIDIs).…”

Rieche formylation of carbon nanotubes – one-step and versatile functionalization route

“…This characteristic was exploited in other studies. 45,46 The weight loss in the range 320-360 C corresponds to thermal decarbonylation in the CNT-CHO, in which formyl groups were covalently attached to the CNT walls. 35 Therefore, functionalization degrees were calculated by a projection of the peak onset and offset points in derivative thermogravimetry (DTG) curves onto the corresponding TGA curves.…”

Folic Acid‐Navigated and β‐Cyclodextrin‐Decorated Carbon‐Encapsulated Iron Nanoparticles as the Nanotheranostic Platform for Controlled Release of 5‐Fluorouracil

“…The controlled release of a drug may lower its side effects and increases its therapeutic effect on tumors. The complexation of 5‐FU or its derivatives (for example tegafur) inside βCD attached to polymeric vectors, carbon materials, or iron oxide nanoparticles, were reported. The in vitro or in vivo studies revealed the therapeutic potential of the designed 5‐FU delivery platforms.…”