Microarchitectonics of single-pore hollow polymeric micromotors based on polyaminoester/polycaprolactone for co-delivery of doxorubicin and curcumin against gastric cancer.

Micromotors have garnered significant interest due to their autonomous locomotion and capabilities for active transport at the micro and nanoscale. This study presents a novel synthesis method for producing single-pore hollow polymeric microspheres (SHPMS) using a dendron-polymer conjugate derived from polyaminoester and polycaprolactone, characterized by its pH-responsiveness and amphiphilicity. The conjugate serves as a partial emulsifier in a one-step water-in-oil-in-water (W/O/W) double emulsion process, allowing for precise morphological control over the microspheres, including adjustments to pore size and internal architecture. Following synthesis, platinum nanoparticles were loaded into the SHPMs, yielding self-propelled micromotors capable of propulsion via the catalytic decomposition of hydrogen peroxide. These micromotors were tailored for the co-delivery of doxorubicin (DOX) and curcumin (CURC) to enhance therapeutic efficacy against gastric adenocarcinoma (AGS and MKN-45) cells. Drug release studies showed excellent pH-responsiveness with markedly increased DOX release in acidic environments. Cytotoxicity assays revealed that the micromotor system exhibited significantly enhanced anticancer activity compared to free DOX, due to the synergistic effects of curcumin as a natural P-glycoprotein (P-gp) inhibitor. This combination not only reduced the required DOX concentration but also maintained therapeutic activity.