Maximizing the Relaxivity of Gd-Complex by Synergistic Effect of HSA and Carboxylfullerene

Abstract

Macromolecular magnetic resonance imaging (MRI) contrast agent Gd-DTPA-HSA (DTPA, diethylene triamine pentacetate acid; HSA, human serum albumin) as a model has been successfully conjugated with trimalonic acid modified C60 for contrast enhancement at clinically used magnetic field strength. The Gd-DTPA-HSA-C60 conjugate exhibit maximal relaxivity (r1 = 86 mM(-1) s(-1) at 0.5 T, 300 K) reported so far, which is much superior to that of the control Gd-DTPA-HSA (r1 = 38 mM(-1 )s(-1)) under the same condition and comparable to the theoretical maximum (r1 = 80-120 mM(-1) s(-1), at 20 MHz and 298 K), indicating the synergistic effect of HSA and carboxylfullerene on the increased contrast enhancement. TEM characterization reveals that both Gd-DTPA-HSA-C60 and Gd-DTPA-HSA can penetrate the cells via endocytosis and trans-membrane, respectively, suggesting the potential to sensitively image the events at the cellular and subcellular levels. In addition, the fusion of fullerene with Gd-DTPA-HSA will further endow the resulting complex with photodynamic therapy (PDT) property and thus combine the modalities of therapy (PDT) and diagnostic imaging (MRI) into one entity. More importantly, the payloaded Gd-DTPA may substitute for other more stable Gd-DOTA and HSA as a theranostic package can further work as a drug delivery carrier and effectively control drug release through proteolysis.

Covalent attachment of Mn-porphyrin onto doxorubicin-loaded poly(lactic acid) nanoparticles for potential magnetic resonance imaging and pH-sensitive drug delivery

“…As shown in Fig. 8a, the r 1 relaxivity of free Mn(III)TPPS3NH 2 is 6.70 mM ÀÀ1 s ÀÀ1 , higher than that of Gd-DTPA (4.5 mM ÀÀ1 s ÀÀ1 ) at the same magnetic field reported in the literature [37]. The higher r 1 relaxivity of Mn(III)TPPS3-NH 2 is mainly attributed to the attractive force between water-soluble porphyrins and the surrounding water molecules.…”

Mn-porphyrin Conjugated Au Nanoshells Encapsulating Doxorubicin for Potential Magnetic Resonance Imaging and Light Triggered Synergistic Therapy of Cancer

“…Fig 7A indicated that the T 1 relaxation time increases as the concentrations of Mn 3+ increasing and the trend is well fit by a linear line within the analyzed range of Mn 3+ concentrations for both free MnP and DOX@PLA@Au-PEG-MnP NPs. At the magnetic field strength of 0.5 T, the r 1 relaxivity of free MnP were measured as 6.70 mM -1 s -1 , higher than that of clinical approved Gd-DTPA (4.5 mM -1 s -1 ) at the same magnetic field strength50. More excitingly, after the covalent linkage of MnP onto the surface of DOX@PLA@Au through PEG chains, this r 1 value significantly increased to 22.18 mM -1 s -1 , which was more than three times as high as that of free MnP (Fig 7A).…”

Biological activity of fullerenes - reality and prospects

“…В контрастных агентах для МРТ на основе фуллеренов сочетаются эффектив-ная диа гностика и лечебный эффект. Например, контрастирующий препарат Gd-DTPA-HSA можно модифицировать трисмалонатом С 60 [77]. И тогда в действии препарата объединятся оба направле-ния -лечебное (фуллереновый кор как фотосен-сибилизатор) и диагностическое (гадолиний как контрастный агент для МРТ).…”