Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily. This type II transmembrane protein is able to bound specifically to cancer cell receptors (i.e., TRAIL-R1 (or DR4) and TRAIL-R2 (or DR5)) and to induce apoptosis without being toxic for healthy cells. Because membrane-bound TRAIL induces stronger receptor aggregation and apoptosis than soluble TRAIL, we proposed here to vectorize TRAIL using single-walled carbon nanotubes (SWCNTs) to mimic membrane TRAIL. Owing to their exceptional and revolutional properties, carbon nanotubes, especially SWCNTs, are used in a wide range of physical or, now, medical applications. Indeed due to their high mechanical resistance, their high flexibility and their hydrophobicity, SWCNTs are known to rapidly diffuse in an aqueous medium such as blood, opening the way of development of new drug nanovectors (or nanocarriers). Our TRAIL-based SWCNTs nanovectors proved to be more efficient than TRAIL alone death receptors in triggering cancer cell killing. These NPTs increased TRAIL pro-apoptotic potential by nearly 20-fold in different Human tumor cell lines including colorectal, nonsmall cell lung cancer, or hepatocarcinomas. We provide thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be useful to future nanomedicine therapies.

Nanovector formation by functionalization of TRAIL ligand on single-walled carbon nanotube: Experimental and theoretical evidences

“…Statistical analyses were performed and showed that an amount of 80% of TRAIL coverage was obtained on most of SWCNT. This lead to increased efficiency of vectorized TRAIL compared to TRAIL alone [14].…”

“…The detail of this synthesis is given elsewhere [14]. Briefly, purified SWCNT are cut in a 3:1 mixture of concentrated sulfuric and nitric acid (96% and 69% respectively), and sonicated in a water bath (Elmasonic model S30H, 50-60Hz, 280W) for 4h, and then vigorously stirred for 12h.…”

“…The laser excitation at 633 nm was provided by a 20 mW helium-neon laser and a reduced laser power (0.125 mW) was required to avoid heating the samples. An x50 microscope objective was used with an acquisition time of 10 s. The intensity of all the resulting Raman spectra were normalized to the intensity of the graphite band (G-band) located at about 1590 cm -1 [14].…”

Malign plevral mezotelyomada ilaç taşıyıcı nanosistemler

“…Aslında sitotoksik ilaç-lar hızlı bir şekilde büyüyen ve bölünen hücrelere toksik şekilde etki edip hücreyi öldüren ya da fonksiyonunu durduran maddeler oldukları için tedavi amacıyla verilen sitotoksik ilacın etken maddesinin tümöre özgün olması ve diğer normal hücrelerde istenmeyen yan etkilerinin oluşmaması için farklı çözümler gelişti-rilmeye çalışılmaktadır. Günümüzde nanotaşıyıcılar terapötik etkinliğin ve güvenliğin geliştirilmesi bakı-mından umut vadetmektedir (23)(24)(25).…”

DFT, QTAIM, and NBO investigations of the ability of the Fe or Ni doped CNT to absorb and sense CO and NO

“…In recent years, the single-wall carbon nanotubes have attracted a great deal of attention because of the tubular structure, high specific surface, high thermal stability, and high chemical stability [2,3]. A large number of investigations have been carried out to research the significances and applications of these CNTs in many fields [4][5][6][7]. Adsorption and storage of gases, such as H 2 , are the most common applications of CNTs [8][9][10][11][12].…”