Chemotherapeutic agents of choice are 5-fluorouracil, gemcitabine, and erlotinib. gemcitabine has been approved by the fda for use as a single agent for the first line treatment of both locally advanced and metastatic cases of pancreatic cancer . although these chemotherapeutics have direct effects on cancerous tissues, the toxicities in normal tissues are usually dose-limiting factors in successful chemotherapeutic regimes. recently, some efforts have been performed to find an appropriate carrier to deliver the drug , but it still needs much further studies. recently nanostructures have found numerous applications and researches on the development of a drug carrier based on the nanostructures
has been rapidly grown. boron nitride (bn) heterofullerenes have been already known as nanostructures with special physical and electronic properties. furthermore, bn heterofullerenes can be functionalized with various biological molecules. in 2009, chen
et al. showed that bn nanostructures are noncytotoxic and can be functionalized for biological applications, and they used bn nanotubes as a carrier to deliver dna oligomers to the cells.these researches tempted us to investigate the ability of b12n12 fullerene as a carrier for gemcitabine drug.
Our calculations are based on the ab initio density functional theory (dft) within three parameter m06/6-31+g** functional. the natural bond orbital (nbo) calculations and all calculations of homo-lumo gaps were also performed at the same level of theory. gaussian09 package was used for all calculations
Results show that mainly the boron atom in b12n12 tends to have an interaction with the oxygen atoms of gemcitabine. their structures have been optimized. we also calculated the change of enthalpy, gibbs free energy and entropy for the adsorption processes at 298 k and 1 atm. for our complexes, the calculated Δg values are less negative compared to the ead, indicating that upon the adsorption process the entropy is decreased because of a reduction of disorder of the system. the calculated negative values of Δs for complexes confirm this matter. the electric dipole moment of b12n12 is calculated to be zero but this value is non-zero for complexes which make them more soluble in polar solvents. the stretching vibrational mode of c-o bonds in the gem molecule is decreased in the complexes indicating that this bond is somewhat weakens upon the adsorption process because of a charge transfer. the values of homo, lumo and eg are also determined. the eg is a useful factor for determining the kinetic reactivity of materials and also its change upon the adsorption process indicates the sensitivity of an adsorbent to an adsorb ate based.the change of eg of adsorbent can help one to recognize the presence and attachment of the drug to the carrier. in one of the complexes, the interaction of bn nanocluster with the drug reduces its eg more than 30% which can help to detect the drug. in this structure, boron atom forms a chemical bond with o1 atom, and its adjacent nitrogen atom forms a hydrogen bond with the hydrogen atom of gem. therefore, there is a relatively strong interaction between gem and b12n12 molecules. the mep plot indicates that the electrostatic potential of n and b atom is largely negative and positive which makes the b sites proper for nucleophilic attack. after interaction with gem, the lumo of fullerene is shifted on the drug molecule in both complexes. the dos plot for b12n12 before and after interaction with gem shows that the lumo level sharply shifts which reduces the eg of the stablest complex. for the others, this decrease is larger and we predict a smaller eg. while there is no significant changes in homo level for b12n12 after the interaction with the gem molecule. moreover, the nbo analysis determines that the charge transfers from the gem to the b12n12 cage for both complexes which are significant.
Using dft calculation, we have studied the gem drug attachment and release to b12n12 nanoclusters to find a new drug delivery system. it is found that the pristine cluster can be a suitable carrier for the gem anti-cancer drug because of the fairly strong interaction with ead of about -11.90 kcal/mol. it was demonstrated that in the low ph of the cancerous tissues the drug can be separated from the cluster by proton attack.