Abstract
Tumor is a prevalent great threat to public health worldwide and multidrug resistance (MDR) of tumor is a leading cause of chemotherapy failure. Nanomedicine has shown prospects in overcoming the problem. Doxorubicin (DOX), a broad-spectrum anticancer drug, showed limited efficacy due to MDR. Herein, a doxorubicin containing pectin nanocell (DOX-PEC-NC) of core-shell structure, a pectin nanoparticle encapsulated with liposome-like membrane was developed. The DOX-PEC-NC, spheroid in shape and sized around 150 nm, exerted better sustained release behavior than doxorubicin loading pectin nanoparticle (DOX-PEC-NP) or liposome (DOX-LIP). In vitro anticancer study showed marked accumulation of doxorubicin in different tumor cells as well as reversal of MDR in HepG2/ADR cells and MCF-7/ADR cells caused by treatment of DOX-PEC-NC. In H22 tumor-bearing mice, DOX-PEC-NC showed higher anticancer efficacy and lower toxicity than doxorubicin. DOX-PEC-NC can improve anticancer activity and reduce side effect of doxorubicin due to increased intracellular accumulation and reversal of MDR in tumor cells, which may be a promising nanoscale drug delivery vehicle for chemotherapeutic agents.
Highlights
Cancer is the leading cause of death and has become a serious public health problem worldwide [1,2]
When DOX-PEC-NP dispersed in dilute hydrochloric acid solution, DOX-PEC-NC with higher DL% was successfully prepared by adding a proper amount of doxorubicin in external aqueous phase
May the PEC-NC affect the uptake and efflux of doxorubicin in drug resistant tumor cell lines to overcome Multidrug resistance (MDR)? Our results showed that the IC50 value of DOX-PEC-NC was much lower than that of doxorubicin solution in HepG2/ADR and MCF-7/ADR cells (Table 4), and it increased the uptake as well as decreased the efflux of doxorubicin in both sensitive and drug resistant tumor cell lines (Fig 7)
Summary
Cancer is the leading cause of death and has become a serious public health problem worldwide [1,2]. Cytotoxicity-based chemotherapy is one of the most commonly used means of cancer treatment [3], the efficacy of chemotherapy is seriously weakened because of the poor tumor targeting of chemotherapeutic agents and acquired chemotherapy resistance of tumors [4,5].
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