The antitumor drug docetaxel (DTX) has limited oral bioavailability. This study aimed to develop novel oral nanoparticles to enhance DTX's absorption and bioactivities. The nanoparticles (H-N-D) were prepared by inducing the self-assembly of a Coptis protein through heating, followed by modification using hydroxypropyl trimethyl ammonium chloride chitosan (HACC). H-N-D was characterized, its effects on DTX's pharmacokinetics and bioactivities were evaluated, and related mechanisms were explored. H-N-D exhibited a spherical morphology, a size of 174.9 ± 1.53 nm, a zeta potential of 19.81 ± 0.79 mV, and good stability in gastric and intestinal fluids. DTX had an encapsulation efficiency of 99.17 ± 0.57 % and a drug loading of 2.95 ± 0.40 %. DTX, originally a crystal, existed as an amorphous form in H-N-D and produces hydrogen bond interactions. H-N-D significantly enhanced DTX's solubility (4.6 times, p <
0.01), release (p <
0.01), metabolic stability (p <
0.05 or p <
0.01), uptake in Caco-2 cells (p <
0.01), and absorption in mouse gut sacs (p <
0.01). Pharmacokinetic studies in mice revealed a 235.2-fold increase in blood AUC