"Nejsmutnějším aspektem života v současné době je to, že věda shromažďuje poznatky rychleji, než společnost shromažďuje moudrost."
Isaac Asimov
Nanomaterials are nowadays attracting enormous attention in almost all research areas. Hence there is no wonder that their application in medicine is so widely explored. Both, diagnostic as well as therapeutic utilization of various types of nanoparticles have been investigated. Metal or semiconductor nanoparticles are employed for imaging applications and visualization, and magnetic particles are utilized for hyperthermia therapy, and variety of other types of nanomaterials is used for drug delivering. Prominent position among nanomaterials used in medicine belongs to carbon nanomaterials such as nanotubes, fullerenes and/or graphene due to their unique physical and chemical properties. The ?-? stacking effect can be utilized for conjugation of aromatic molecules onto the polyaromatic surface of all carbon nanomaterials.
2. Current diagnostics of prion protein related diseases
Diagnostics of infectious diseases is a relatively well-established area. It can be done either by the immunologic methods or by the amplification of a nucleic acid specific to infectious agent using polymerase chain reaction (PCR) 16. However, in TSEs, the infectious agent, prion protein, has the same sequence of nucleic acids as a naturally occurring protein. The other issue with the diagnosing based on the PrPSc detection is that the pathological form of PrP is abundant only at late stages of the disease in a brain. Therefore, the diagnostics of prion protein caused diseases represent a sort of challenges 17 as that hosts can incubate infectious prion proteins for many months or even years. During this period, they exhibit no overt clinical symptoms. Incubation period for some human prion diseases can be as long as 40 years 18. The incubation time of the first human transmissible spongiform encephalopathy “Kuru” described by Prof. Gajdusek in the late 1950s was estimated within the range from 21 to 40 years 19, 20.
Moreover, fullerenes and their derivatives were studied for their efficient quenching of various free radicals and reactive oxygen species, thus potentially serving as radical scavengers and/or anti-oxidants in biological systems protecting from the oxidative stress and toxicity caused by cytostatic drugs [1-4]. The combination of the protective properties of fullerenes and their ability of drug delivery make them very attractive for anti-cancer therapy [5, 6]. For the clinically highly effective anticancer drug paclitaxel, it was shown that covalent conjugate with C60 for a lipophilic slow-release system enhanced the therapeutic efficacy [7]. Doxorubicin (DOX), another highly effective cytostatic drug in antitumor therapy [8], was also conjugated with fullerenes and carbon nanotubes aiming at mitigating DOX-induced toxic side-effects [1, 9, 10] and/or improving the drug delivery [11-14]. Moreover, the optical properties of DOX provide opportunities to track the molecules and conjugates by using fluorescence-based techniques, such as assessing nanocarrier of DOX in cells without any other fluorescence labels [15]. Generally, the coupling between DOX and fullerene surface can be assured by covalent linkage [6, 16], or by nonspecific interaction after activation of the surface by acidic oxidation [11].
In this study, the simple method of fullerene-doxorubicin conjugation is utilized and the characterization of conjugates by spectral methods, electrochemical analysis, capillary electrophoresis and liquid chromatography is demonstrated. Finally, the monitoring of the effect of prepared conjugates on the bacterial cells as well as in vivo imaging on the chicken embryo is presented. The DOX is effective cytostatics, however, exhibiting severe side effect, which can be eliminated by number of approaches [31]. One of them is the conjugation with fullerenes which have proven to have protective properties against the DOX toxicity. Concurrently, fullerenes increase the size of the DOX molecule and therefore the time before the drug is eliminated from the organism is prolonged. In this study we demonstrated the conjugation procedure for formation of the DOX-fullerene complexes and their characterization by optical and electrochemical method. Finally, in vivo monitoring of the conjugates in the chicken embryos was performed investigating their distribution in the particular organs of the chicken embryo.
Podpořeno projekty: CYTORES GA CR P301/10/0356
30— 2013
30— 2013
29— 2013
28— 2013
27— 2013
26— 2013
25— 2013
24— 2013
23— 2013
22— 2013
21— 2013
20— 2013
19— 2013
18— 2013
17— 2013
16— 2013
15— 2013
14— 2013
![]() | Zemědělská 1/1665 613 00 Brno Budova D | Tel.: +420 545 133 350 Fax.: +420 545 212 044 | ![]() |
![]() |