Abstract
Docetaxel (DTX) has been widely used for the treatment of many types of cancer. However, DTX is poorly water-soluble and commercial DTX is formulated in non-ionic surfactant polysorbate 80 and ethanol, thereby leading to hypersensitivity and serious side effects. Herein, a polymer dual drug conjugate was synthesized by coupling DTX and docosahexaenoic acid (DHA) with bifunctionalized dextran. The polysaccharide conjugate dextran-DHA-DTX possessed high water solubility and was self-assembled into nanoparticles with a diameter of 98.0 ± 6.4 nm. Pharmacokinetic and biodistribution studies showed that the dextran-DHA-DTX dual drug conjugate not only had significantly prolonged blood circulation but was also selectively accumulated in the tumor with reduced drug distribution in normal tissues. The conjugate exhibited a superior therapeutic effect in both xenograft nude mice models without causing any systemic side effects. Notably, the conjugate nearly eliminated all xenograft tumors in nude mice bearing breast cancer cells MCF-7. This study revealed that the dextran-based dual drug delivery system may provide an effective strategy to selectively deliver DTX to tumor sites.
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