Combining dual drugs in one vehicle to
cancer cells offers spatiotemporal localization of
drug at the site of action, leading to synergistic
therapeutic effects and reduced side effects. To improve pH/redox responsiveness to the tumor microenvironments for
cancer therapy, a pH/redox-responsive
micelle based on poly(ε-
caprolactone)-SS-poly(
methacrylic acid) (PCL-SS-
PMAA) diblock copolymer was fabricated for dual
drug delivery. The PCL-SS-
PMAA was formulated into a core-shell
micelle (PSPm) in an aqueous
solution. The critical
micelle concentration (CMC) values of PSPm were 7.94 × 10-3 mg mL-1 at pH 5.0 and 1.00 × 10-2 mg mL-1 at pH 7.4. The hydrodynamic diameters of PSPm were within 210-270 nm, depending on pH values. Changes in morphology and size of PSPm were clearly observed before and after exposure to a
reducing agent.
Paclitaxel (PTX) was encapsulated into the core and
cisplatin (CDDP) was chelated on the shell of PSPm, with both PTX and CDDP being efficiently released from PSPm in the presence of a
reducing agent in an
acid condition. MTT and
annexin V/
propidium iodide dual staining results demonstrated that co-loading of CDDP and PTX into PSPm had a synergistic effect in killing
lung cancer cells and exerted superior antitumor activity over the combination of single
drug-loaded PSPm or the combination of free-CDDP and free-PTX at equivalent
drug amounts. Hence, encapsulating the dual drugs into PSPm exhibits a synergistic effect for potential
lung cancer therapy.