Biology subjects

Kanchi, S.

Publications and source records attributed to Kanchi, S..

2 recordsLinked to original sources

bioRxiv2026

Surface Functionality and pH Govern Structural Dynamics and Drug Binding in PETIM and PAMAM Dendrimers

1.Surface functionality and pH play a decisive role in governing the structural dynamics, hydration, and drug-binding behaviour of dendrimers. Here, all-atom molecular dynamics (MD) simulations were performed on five generations of PAMAM (G1-G5) and PETIM (G2-G6) dendrimers with O-core and N-core architectures, functionalized with amine, carboxylic acid, or sugar terminal groups under different protonation states. Protonation of the tertiary branch-point amines expands the dendrimer structure, increases internal porosity and hydration, and enhances structural fluctuations across both families. In contrast, non-protonated amine -NH2 (NP) and carboxylic acid -COOH (NP) terminated dendrimers, together with deprotonated carboxylate-COO- (DeP) systems, retain comparatively compact conformations. Sugar-functionalized dendrimers ({beta}-galactose-terminated PETIM and D-glucose-terminated PAMAM) are most hydrated and structurally rigid, whereas amine-terminated dendrimers exhibit the greatest conformational dynamics. PAMAM dendrimers with -NH2, -NH3+, and -COO- terminal groups are generally more hydrated than their PETIM counterparts. However, {beta}-galactose-terminated PETIM dendrimers are more hydrophilic than D-glucose-terminated PAMAM dendrimers. N-core PETIM dendrimers also adopt more compact and spherical conformations than equivalent O-core PETIM dendrimers. Drug-binding MD simulations show that curcumin binding is dominated by van der Waals (vdW) interactions, whereas doxorubicin complexation is primarily driven by electrostatic interactions. Among the investigated surface functionalities, -NH2 (NP), -NH3+ (P), -COOH (NP), and -COO- (DeP) terminations exhibit the most favourable drug-binding characteristics. Except for deprotonated carboxylate systems, curcumin binds more strongly than doxorubicin. Overall, these findings establish molecular-level relationships between surface functionality, protonation state, dendrimer architecture, and drug-binding behaviour, providing design principles for pH-responsive dendrimer nanocarriers with enhanced drug-loading and controlled-release performance. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/742721v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1b63094org.highwire.dtl.DTLVardef@2f81f2org.highwire.dtl.DTLVardef@fc651forg.highwire.dtl.DTLVardef@530a04_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2026

Curcumin - Gold Nanocomposites for Enhanced Doxorubicin Delivery: Molecular Mechanisms of Loading and Membrane Interactions

Curcumin-functionalized gold nanoclusters are promising platforms for catalysis and drug delivery, however, the molecular determinants governing their stability, morphology, and solvent response remain poorly understood. Here, microsecond all-atom molecular dynamics simulations were employed to investigate a 2 nm gold nanoparticle noncovalently coated with different curcumin forms, including the neutral enol and trans-keto tautomers, the deprotonated enolate, and their mixtures in water-ethanol and water-methanol solvents. Region-resolved analyses of the radius of gyration, density profiles, and surface coverage reveal that neutral enol and trans forms generate compact assemblies with near-complete surface coverage, whereas enolate-rich systems adopt more expanded conformations with greater solvent exposure. Mixed systems preserve these intrinsic packing characteristics while improving overall surface coverage. Solvent substitution from ethanol to methanol reduces {pi}-{pi} stacking, strengthens Au-curcumin interactions, and increases surface coverage, yielding more compact nanostructures. Free energy and potential of mean force calculations further indicate that deprotonated curcumin most effectively screens Au-Au interactions and promotes nanoparticle dispersion, whereas the neutral tautomers provide moderate stabilization. Curcumin functionalization also enhances the loading of the anticancer drugs doxorubicin (DOX) and niraparib (NIR) onto Au nanoparticles. Membrane interaction with AuDOX/NIR-Curcumin simulations show that Enolate(An)-containing systems form more extended structures and interact more weakly with both negatively charged and neutral DMPC membranes. In contrast, neutral curcumin complexes form compact, positively charged assemblies with stronger interactions with the negatively charged model membrane. Furthermore, these interactions are predominantly driven by electrostatic attraction and are substantially weaker with the neutral DMPC membrane. Overall, these findings demonstrate how curcumin tautomeric state and solvent environment cooperatively govern interfacial organization and colloidal stability, drug-loading, and membrane interactions. This provides molecular-level design principles for curcumin-based gold nanocarriers for catalysis, sensing, and drug delivery applications.

biophysics↗