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Ligands were anchored onto nanoparticles (NPs) to improve the cell internalization and tumor localization of chemotherapeutics. However, the clinical application was shadowed by the complex preparation procedure and the immunogenicity and poor selectivity and stability of ligands. In this study, a novel strategy was developed to elevate the tumor cellular uptake and tumor localization of NPs utilizing the G2/M phase retention effect of docetaxel, one of the most common chemotherapeutics. Results showed pretreatment with docetaxel could effectively arrest cells in G2/M phase, leading to an enhanced cell uptake of NPs, which may be caused by the facilitated endocytosis of NPs. In vivo imaging and slice distribution also demonstrated the pretreatment with docetaxel improved the localization of NPs in tumor. This strategy can be easily transferred to clinical for cancer management. Combination chemotherapeutics injections with commercial nano-drugs may result in better antitumor effect than the administration of a single drug.

Pretreatment with chemotherapeutics for enhanced nanoparticles accumulation in tumor: the potential role of G2 cycle retention effect