Aqueous Compatible Fullerene−Doxorubicin Conjugates

Abstract

Covalent conjugates of fullerene C 60 and the highly effective anticancer drug doxorubicin (DOX) were prepared and studied. The conjugation was through the amide linkage to preserve the intrinsic properties of DOX and fullerene cage. As designed, the conjugates with hydrophilic ethylene glycol spacers exhibited much improved aqueous compatibility, with significant solubility in water-DMSO mixtures. The anti-neoplastic activities of DOX were apparently unaffected in the conjugates according to evaluations in vitro with a human breast cancer cell line.

Possibilities to increase the effectiveness of doxorubicin in cancer cells killing

“…Lu et al (2009) synthesized conjugate III with two hydrophilic tethers and two DOX-unit sandwiches. The conjugate III is structurally flexible because of the ethylene glycol spacers, making the attached DOX units readily available for their therapeutical functions.…”

“…The conjugate III is structurally flexible because of the ethylene glycol spacers, making the attached DOX units readily available for their therapeutical functions. When cytotoxicity of conjugate III and free DOX was compared, the viability of MCF-7 cells exposed to the conjugate III decreased in a dosedependent manner, with approximately half the cell viability inhibited at the DOX-equivalent concentration of 25 µg/mL (Lu et al, 2009).…”

“…The results suggested that the conjugate was distributed mostly in the cytoplasm, which differs significantly from free DOX molecules distributed predominantly in the cell nucleus. Lu et al (2009) investigated methoxymorpholinyl-DOX conjugate (MM-DOX), a novel CYP3A4-activated anticancer prodrug. Retroviral transfer of CYP3A4 increased by 120-fold cancer cell chemosensitivity to MM-DOX.…”

Fullerene derivatives as nano-additives in polymer composites

“…18). 321 Since highly effective anticancer drug DOX possesses strong absorption and fluorescence in the visible region, incorporation of two DOX units into the fullerene core enables the tracking of DOX-containing conjugates by optical techniques. It was found that conjugate XI was distributed mostly in the cytoplasm, which is significantly different from free DOX molecules predominantly accumulated in the cell nucleus.…”

“…Fullerene C60 derivative tethered to two doxorubicin units (XI). 321 this conjugate, the two specific ligands provide synergistic targeting effects, high targetability, and hence a dramatically increased uptake of the nanoplatform by cancer cells. High yield of 1 O 2 due resonance energy transfer between APBA-UCNPs (donor) and HA7C 60 (acceptor) also favours effective therapy.…”