Abstract
Chemotherapy has been one of the major standard treatments for a variety of cancers. cis-Dichlorodiamminoplatiunum (II) (cisplatin, CDDP), as one of the anticancer agents, demonstrated excellent efficacy against tumor and has been an indispensable component in chemotherapy, chemoradiation, chemo-molecular targeted therapy and chemo-immunotherapy. However, its therapeutic concentration was limited since its inevitable toxicity. Previously, we have constructed CDDPloaded nanoparticles (NPs) with mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HOPCL) by a facile method. The most optimal proportion of the two copolymers was selected through a series of physical, chemical, cytological and histological evaluations. In the present study, we explored the mechanisms of NPs and observed the in vivo antitumor effect after administrating CDDP-loaded PEG-PCL NPs. Positron emission tomography as well as computed tomography (PET/CT) were adopted for detecting tumoral metabolic activity. Images from fluorescence microscope revealed superior cellular uptake of CDDP-loaded NPs with rhodamine B aggregated intracellularly in cancer cells. Similar apoptotic rates between free CDDP group and CDDP-loaded NPs group was measured by flow cytometry. Tumor volumes and murine weights confirmed the superiority of CDDP-loaded NPs in therapeutic efficacy as compared with free CDDP. Blood tests showed milder side effects in CDDP-loaded nanoparticle group. PET/CT images illustrated less uptake intensity of FDG in mice received CDDP-loaded NPs than free CDDP. Our results suggest that PEG-PCL/PCL NPs could be a promising antitumor drug carrier for CDDP delivery with solid efficacy and minor side effects.
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