New insights into Hexakis macrocycles as a novel nano-carrier for highly potent anti-cancer treatment: A new challenge in drug delivery

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The purpose of this study is to design and evaluate a new tubular assembly structure of Hexakis (m-phenylene ethynylene) (m-PE) macrocycles and to explore its potential application as an innovative drug delivery system. First, we focused on how (m-PE) macrocycles can be self-assembled in both chloroform (CHCl3) and water solvents for the formation of the assembled nanotube using molecular dynamics (MD) simulations. In contrast to their behavior in water solvent, all ten (m-PE) macrocycles remain aggregated at low concentrations of CHCl3. We found that these macrocycles carrying chiral side chains and capable of H-bonded self-association, assemble into tubular stacks. Then, the dual delivery strategy for the transport of doxorubicin (DOX) and curcumin (Cur) on the self-assembly system of hexakis (m-PE) nanocarrier is examined using molecular dynamics (MD) simulation and free energy calculation. The obtained results indicated that the binding energy of DOX (− 298.9 kJ/mol) on hexakis (m-PE) in the presence of Cur is higher than free DOX (− 247.7 kJ/mol). Furthermore, in the interaction of the DOX and hexakis m-PE, the contribution of van der Walls (vdW) energy is higher than electrostatic (elec) energy, which can be related to the strong π-π interactions between the drug molecules with the carrier surface. In general, the results indicated that the simultaneous delivery of DOX and Cur through DOX/Cur/hexakis (m-PE) could be a promising vehicle in tumor therapy. Based on the obtained results of the present research, hexakis (m-PE) macrocycle can be used as a drug delivery vehicle for targeted or systemic delivery.