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Biomed Pharmacother. 2019 Apr;112:108614. doi: 10.1016/j.biopha.2019.108614. Epub 2019 Feb 21.

Lung cancer therapy using doxorubicin and curcumin combination: Targeted prodrug based, pH sensitive nanomedicine.

Author information

1
Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
2
Department of Oncology Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
3
Department of Oncology Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China. Electronic address: mahlxjtu@sohu.com.

Abstract

Lung cancer is the leading cause of cancer death worldwide. To overcome the toxic side effects and multidrug resistance (MDR) during doxorubicin (DOX) chemotherapy, a urokinase plasminogen activator receptor (uPAR) targeting U11 peptide decorated, pH-sensitive, dual drugs co-encapsulated nanoparticles (NPs) system is employed in this study. A U11 peptide conjugated, pH-sensitive DOX prodrug (U11-DOX) was synthesized and used as materials to produce NPs. A curcumin (CUR) and U11-DOX co-encapsulated NPs system (U11-DOX/CUR NPs) was constructed to treat lung cancer. After the characterization of biophysical properties of this NPs system, synergistic chemotherapeutic efficacy was evaluated in both cultured cancer cells and tumor-bearing animal model. U11-DOX/CUR NPs had a uniformly spherical shape with a core-shell structure. The mean particle size and zeta potential of the U11-DOX/CUR NPs was 121.3 nm and -33.5 mV, with a DOX and CUR EE of 81.7 and 90.5%, respectively. The DOX release from U11-DOX/CUR NPs was 83.5, 55.2, and 32.8% correspondence to the pH of 5.0, 6.0 and 7.4. Cellular uptake efficiency of U11-DOX/CUR NPs was significantly higher than non U11 peptide decorated DOX/CUR NPs. U11-DOX/CUR NPs displayed a pronounced synergy effects in vitro and an obvious tumor tissue accumulation efficiency in vivo. In vivo antitumor experiment showed that U11-DOX/CUR NPs could inhibit the tumor growth to a level of 85%.In vitro and in vivo studies demonstrated that U11-DOX/CUR NPs is a sustained released, pH responsive, synergistic antitumor system. This study suggests that the U11-DOX/CUR NPs have promising potential for combination treatment of lung cancer.

KEYWORDS:

Curcumin; Doxorubicin; Lung cancer; Urokinase plasminogen activator receptor; pH sensitive

PMID:
30798129
DOI:
10.1016/j.biopha.2019.108614
[Indexed for MEDLINE]
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