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

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^-1 for C_∨-C_||, BN_∨-BN_||, C_∨-BN_||). The potential of mean force calculations reveal energy barriers scale as Δ<i>G</i> ∝ 1/<i>R</i>², with BN nanotubes showing 20-30% higher barriers (e.g., -19.63 vs -14.14 kcal·mol^-1 for graphene) due to stronger van der Waals interactions. In the BN_∨-C_|| 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.