PH responsible and fluorescent Cy5.5-PEG-g-A-HA/CDDP complex nanoparticles: synthesis, characterization, and application for targeted drug delivery.

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Clinical application of cisplatin (CDDP) against various solid tumors is often limited due to its poor selectivity and severe side effect. Considering this, in our study, CDDP was incorporated in fluorescent PEG amine grafted aldehyde hyaluronic acid by imine bond and metal ion coordination bond linking and formed a complex, the complex was then self-assembled into nanoparticles in water simply. FT-IR, XRD, DLS and SEM analysis demonstrated that the nanoparticles were prepared successfully and exhibited a spherical structure with size ranged from 216.4 to 372.3 nm in diameter. CDDP releasing from the nanoparticles was in a controlled manner, and had faster release rate at lower pH, indicating the nanoparticles were responsive to tumor micro-acid environment. Since fluorescent Cy5.5 and targeting hyaluronic acid existed on the surface of the nanoparticles, CLSM images clearly showed that the nanoparticles could target and internalize into HeLa cells, and then inhibited the growth of HeLa cells. In addition, MTT, AO-EB staining, and hemolysis assay showed that the nanoparticles had good cyto-/hemo-compatibility. Hence, the nanoparticles had the potential to be used for cancer therapy and diagnosis. The further in vivo experiment will be shown in the next work. pH responsible and fluorescent Cy5.5-PEG-g-A-HA/CDDP complex nanoparticles were facilely fabricated for controlled and targeted delivery of CDDP.