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Gemcitabine-camptothecin conjugates: a hybrid prodrug for controlled drug release and synergistic therapeutics.

Biomaterials Science 2017 August 23
Drug self-delivery systems represent an important approach to enhance the therapeutic efficacy for cancer therapy. We report the design, synthesis and characterization of a new amphiphilic small molecule prodrug based on two types of anticancer drugs, the hydrophilic gemcitabine and hydrophobic camptothecin, linked by a disulfide bond and abbreviated as GT-CPT. The obtained amphiphilic prodrug conjugates self-assembled into nanoparticles in water and showed strong micellar stability and excellent blood compatibility in vivo. The GT-CPT prodrug conjugates could realize precise drug loading as high as ∼75 wt% demonstrating a carrier-free model for efficient drug delivery. Furthermore, the reduction-responsive disulfide bond enabled controlled drug release in the presence of tumour-specific microenvironment. It was found that each of these hybrid drug components (CPT and GT) not only showed enhanced cytotoxicity individually but also exhibited a prominent synergistic effect on HeLa and MCF-7 cancer cells. This study demonstrated the promising potential of this stimuli-responsive hybrid prodrug conjugate for highly efficient co-delivery of multiple anticancer chemotherapeutics, which could inspire further applications using such hybrid prodrug conjugates for combination cancer chemotherapy.

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