Research On The Dynamics Theoretical Model Of Drug Macromolecule Transport Through The Nuclear Pore Complex

With the development of gene therapy and new cancer-fighting drug which can directly acting on DNA, nuclear drug delivery for cancer chemotherapy is drawing extensive attention recently. Nuclear delivery of chemotherapeutic drugs which can increase the therapeutic efficacies and minimize the side effects has a promising future. However, low drug absorption efficiency of tumor cells limits the applications of new cancer-fighting drug. So researches on the mechanism of nuclear drug delivery come to the forefront.A microscopic transport model of drug molecular translocate through the nuclear pore complex (NPC) is presented based on Self-consistent field theory. In this theoretical model, external potential, Coulomb electrostatic potential of charged ions (electrolyte effect), attractive interaction between polymer and nuclear pore complex (the excluded volume effect, drag effect of NPC, and hydrophobic effect) are all be considered having effect on free energy landscape and conformation entropy during translocation stage. Distribution of nucleoporins (Nups) and the influence rules of various parameters (such as chain length of drug molecular, length of NPC, strength of hydrophobic function and excluded volume effect) on translocation time are studied through theoretical analysis and numerical calculation. Numerical simulation results show that depletion layer of the center of nuclear pore complex of nucleoporins can facilitate the translocation of drug molecular. Further studies indicate that the curve of translocation time is concave with the increasing of the length of NPC and charge number of drug molecular. In other word, there is a critical value of the length of NPC and charge number of drug molecular in which the translocation time takes minimal value. The stronger the hydrophobic effect, the shorter the translocation time. Furthermore, the translocation time decreases with the increasing of excluded volume effect. Therefore, the results can provide theoretical basis for the clinical application of nuclear drug delivery.