Unidirectional Drug Delivery and Responsive Release Guided by Nanofunnel-Shaped Heterojunction.

Luo, Jun; Huang, Changxiong; Liao, Zhenyu; Ma, Xinyao; Si, Ting; Chen, Huan; Li, Zhen; Fan, Jun · Nano Lett · 2025

basic_science · Level V

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Abstract

Drug resistance often involves preventing drug entry or expelling drugs from cells, severely affecting the therapeutic effect. We propose nanofunnel-shaped devices by pairing truncated graphene/boron nitride nanocones and nanotubes using curvature gradients and material properties to modulate energy barriers for unidirectional drug delivery. Molecular dynamics simulations demonstrate spontaneous delivery across models (Δ<i>G</i> = -14.14 to -27.87 kcal·mol<sup>-1</sup> for C<sub>∨</sub>-C<sub>||</sub>, BN<sub>∨</sub>-BN<sub>||</sub>, C<sub>∨</sub>-BN<sub>||</sub>). The potential of mean force calculations reveal energy barriers scale as Δ<i>G</i> ∝ 1/<i>R</i><sup>2</sup>, with BN nanotubes showing 20-30% higher barriers (e.g., -19.63 vs -14.14 kcal·mol<sup>-1</sup> for graphene) due to stronger van der Waals interactions. In the BN<sub>∨</sub>-C<sub>||</sub> model, increasing the tube radius (9.59 to 20.34 Å) or decreasing the cone angle (180-60°) can flip Δ<i>G</i>, enabling bidirectional control. This curvature-material synergy bypasses efflux mechanisms, offering a tunable platform to combat drug resistance and enhance therapeutic precision.

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