Doxorubicin (DOX), a kind of wide-spectrum chemotherapeutic drug, can cause severe side effects in clinical use. To enhance its antitumor efficacy while reducing the side effects, two kinds of nanoparticles with desirable compositions and properties were assembled using optimally synthesized hydroxyethyl starch-grafted-polylactide (HES-g-PLA) copolymers and utilized as partner nanocarriers. The large empty HES-g-PLA nanoparticles (mean size, ca. 700 nm), at an optimized dose of 400 mg/kg, were used to block up the reticuloendothelial system in tumor-bearing mice 1.5 h in advance, and the small DOX-loaded HES-g-PLA nanoparticles (mean size, ca. 130 nm) were subsequently applied to the mice. When these partner nanocarriers were administered in this sequential mode, the released DOX had a significantly prolonged plasma half-life time and much slower clearance rate as well as a largely enhanced intratumoral accumulation as compared to free DOX. In vivo antitumor studies demonstrated that the DOX-loaded HES-g-PLA nanoparticles working together with their partner exhibited remarkably enhanced antitumor efficacy in comparison to free DOX. In addition, these HES-g-PLA partner nanocarriers showed negligible damage to the normal organs of the treated mice. Considering safe and efficient antitumor performance of DOX-loaded HES-g-PLA nanoparticles, the newly developed partner nanocarriers in combination with their administration mode have promising potential in clinical cancer chemotherapy.
Keywords: cancer chemotherapy; doxorubicin; hydroxyethyl starch copolymer; nanoparticle; partner carrier; polylactide.