Liposome formulation of fullerene-based molecular diagnostic and therapeutic agents

Abstract

Fullerene medicine is a new but rapidly growing research subject. Fullerene has a number of desired structural, physical and chemical properties to be adapted for biological use including antioxidants, anti-aging, anti-inflammation, photodynamic therapy, drug delivery, and magnetic resonance imaging contrast agents. Chemical functionalization of fullerenes has led to several interesting compounds with very promising preclinical efficacy, pharmacokinetic and safety data. However, there is no clinical evaluation or human use except in fullerene-based cosmetic products for human skincare. This article summarizes recent advances in liposome formulation of fullerenes for the use in therapeutics and molecular imaging.

Figure 1

Structures of trimetallic nitride endohedral metallofullerene and empty cage fullerene C₇₀.

Figure 2

Three types of fullerene liposomes incorporating un-derivatized fullerenes, lipophilic fullerenes and amphiphilic fullerenes, respectively.

Figure 3

Vesicle formation of amphiphilic fullerene compound ALM with auxiliary phospholipids.

Figure 4

Fullerenes attenuate inflammatory arthritis of the K/BxN-induced disease pathology. (A) Serum-treated mice demonstrated typical synovial hyperplasia, pannus formation and inflammatory infiltrates; (B) By contrast, ALM-treated animals had less evidence of clinical joint inflammation compared with (C) non-diseased animals. ALM: Amphiphilic liposomal malonylfullerene.

Figure 5

Figure: Plaque imaging of aorta arch of 23 weeks old female ApoE^−/− mice with 7T imager. Top: ATCA (100µL, 4.0 mg/kg or 0.9 mg Gd/kg); Bottom: Non-targeted control did not enhance any contrast. Graph: Quantification of signal enhancement. The signal to noise ratio (SNR) was calculated using a reference ROI next to the plaque lesion, then SNR values were normalized to the pre-injection SNR value. The same regions were traced throughout all imaging points. ATCA: white bars, and non-targeted control: black bars. The SNR values are shown as mean for the entire aorta of five mice. * indicates significance (p < 0.05).