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 (ΔG = -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 ΔG ∝ 1/R(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 ΔG, enabling bidirectional control. This curvature-material synergy bypasses efflux mechanisms, offering a tunable platform to combat drug resistance and enhance therapeutic precision.