Doxorubicin combined with betulinic acid or lonidamine in RGD ligand-targeted pH-sensitive micellar system for ovarian cancer treatment.

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ID: 61392
2019
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Abstract
Synergistic combination therapy involving the integration of chemotherapeutics and chemosensitizers into micelles has demonstrated great potential for tumor-specific location release. Here, the natural product betulinic acid (BA) and chemical drug lonidamine (LN) were used as chemosensitizers in combination with doxorubicin (DOX) for ovarian cancer treatment. We designed pH-sensitive peptide derivatives and constructed an all-in-one multifunctional multidrug pH-sensitive targeting delivery system for the synergistic co-delivery of DOX and BA (or LN). The combination of DOX and BA was found to elicit better therapeutic effects and lower cardiotoxicity than the DOX and LN combination in Skvo3 cells. Further, loading DOX/BA into the present micellar systems enabled burst release at the tumor location, leading to enhanced anti-tumor effects and reduced off-target effects. More importantly, DOX/BA micelles elicited fewer adverse effects on cardiac function and leukocyte counts in Skvo3 subcutaneous xenograft models. These features suggest that the designed micelles represent a promising multifunctional strategy for the efficient treatment of ovarian cancer.
Reference Key
jin2019doxorubicininternational Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Jin, Xin;Zhou, Jianping;Zhang, Zhenhai;Lv, Huixia;
Journal International journal of pharmaceutics
Year 2019
DOI
S0378-5173(19)30796-3
URL
Keywords
doxorubicin betulinic acid lonidamine ovarian cancer therapy ph-responsive micelles

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