Artificial Bacteriophage for Anticancer Drug Delivery

J. Velasco-Medina, J.M. Espinosa-Duran, J.C. Arce-Clavijo

Keywords: artificial bacteriophage, nanostructures, nanocontainer, cancer


In this work, we present a new nanodevice, called artificial bacteriophage, name inspired in the Bacteriophage T4. The nanodevice is made up of two carbon nanostructures and molecular bioreceptors: 1) the nanocontainer, made of fullerenes (C240, C540, C960, C2160), serves as the carrier of the drug; 2) nano-needle or nano-syringe, made of carbon nanotubes (SWCNT), serves to inject the drug into the cancer cell through the TRPV1 channel; 3) nanosensors or bioreceptors, made of proteins, serve for the biological recognition of proteins expressed in the TPRV1 channel; The bio-receptors are used to carry out the bind or link with the diseased cell receptors to allow the drug in the nanocontainer and the nano-needle can to be injected. In Figure 1 is shown the artificial bacteriophage. The nanodevice (nanorobot or nanomachine) can be used in "conventional" treatments like chemotherapy, in order to effectively delivery the anti-cancer drugs or it can be used to transport genes in genetic manipulation applications or in nano-anesthesiology, etc. The nanodevice safely transports the drug to the cancer cells, without being destroyed and with a precise arrival. In addition, it could deliver controlled and localized doses of the drug in order to avoid destroying healthy cells and reduce the side effects of the drug. The research results shown that the TRPV1 channel can be a potential target for cancer therapy using carbon-based drug delivery systems. Carbon nanostructures are being considered for the design of drug delivery systems (DDSs) due to their capacity to internalize molecules and control their release. However, for cellular uptake of drugs, this approach requires an active translocation pathway or a channel to transport the drug into the cell. To address this issue, it is suggested to use TRPV1 ion channels as a potential target for drug release by nano-DDSs since these channels are overexpressed in cancer cells and allow the permeation of large cationic molecules. Considering these facts, this work presents three studies using molecular dynamics simulations of a human TRPV1 (hTRPV1) channel built here. The purpose of these simulations is to study the interaction between a single-wall carbon nanotube (SWCNT) and hTRPV1, and the diffusion of doxorubicin (DOX) across hTRPV1 and across a POPC lipid membrane. The first study shows an attractive potential between the SWCNT surface and hTRPV1, tilting the adsorbed SWCNT. The second study shows low diffusion probability of DOX across the open hTRPV1 due to a high free energy barrier. Although, the potential energy between DOX and hTRPV1 reveals an attractive interaction while DOX is inside hTRPV1. These results suggest that if the channel is dilated, then DOX diffusion could occur. The third study shows a lower free energy barrier for DOX across the lipid membrane than for DOX across hTRPV1. Taking into account the results obtained, it is feasible to design novel nano-DDSs based on SWCNTs to accomplish controlled drug release into cells using as translocation pathway, the hTRPV1 ion channel. In Figure 2 is shown the diffusion of DOX across the hTRPV1 channel.