Construction of a Novel Doxorubicin Nanomedicine Using Bindarit as a Carrier: A Multiscale Computer Simulation-Assisted Design-Based Study

Anjie Shi,Ling Long,Chengyuan Zhang,Qingjia Gong,Zhibin Liu,Xing Zhou,Yao Liu,Hongfeng Yuan,Ruibing Wang

doi:10.1155/2021/1835639

Abstract

Nanomedicines typically use polymeric materials or liposomes as carriers. This provides targeting advantages but may lead to a series of defects, such as low drug loading, high risk in terms of safety, and high production costs. Herein, we report a computer simulation-assisted designing method for the construction of a novel doxorubicin (DOX) nanomedicine without any polymer carriers. We used a small molecular drug, bindarit (BIN), as a carrier of DOX to provide synergistic antitumor effects. First, the intermolecular forces between DOX and BIN were calculated for evaluating the interaction and potential conformation of the DOX/BIN complex. Then, the potential assembly ability of the DOX/BIN complex was predicated here by using dissipative particle dynamic stimulation. These computational simulation results suggested that BIN could form an amphiphilic complex with DOX through π–π stacking, hydrogen bonding, and electrostatic interaction and then self-assemble to nanoaggregates at the mesoscopic scale. Under the computational guidance, doxorubicin/bindarit nanoparticles (DOX/BIN NPs) in a spherical morphology were successfully prepared, and these NPs possess the original cytotoxic activity of DOX. Thus, this multiscale computer simulation-assisted design strategy can serve as an effective approach to develop nanomedicines using small molecules as a carrier.

Highlights

Chemotherapy is a widely used strategy for the treatment of tumors
The strong intermolecular interactions (π–π stacking and H-bonding) between DOX and BIN were calculated as a basis for supporting the formation of a stable DOX/BIN complex
A mesoscopic simulation based on DPD methodology further demonstrated that the DOX/BIN complex can self-assemble to spherical aggregates wherein DOX is concentrated internally and BIN on the outer surface

Summary

Introduction

Chemotherapy is a widely used strategy for the treatment of tumors. Traditional chemotherapeutic drugs usually have evident disadvantages such as toxicity to normal cells, poor precision, and multidrug resistance [1]. An increasing number of traditional chemotherapeutic drugs are prepared as nanomedicines, which provides improved antitumor efficiency and reduced side effects, compared to the drugs alone [2]. These nanomedicines are usually prepared with a large amount nonactive excipients as carriers, such as liposomes [3, 4], polymers [5], and inorganic nanoparticles [6]. The use of these excipients as basic materials for the formation of nanomedicines may lead to several problems, such as low drug loading, high risk in terms of safety, and high production costs [7] These limitations negatively impact the prospects of these nanomedicines in clinical use. Researchers are committed to developing strategies to reduce the proportion of inactive substances in nanomedicines through supramolecular assembly and other approaches, to achieve higher drug loading, increased drug safety, and simpler preparation methods

Methods

Results

Conclusion