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Preparation of mitochondrial targeted calcium arsenite/doxorubicin lipid nanoparticles and the in vitro study in reversing tumor drug resistance
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Ke ZHANG1, Tian-xiang YUE1, Meng-ying CHENG1, Zeng-ying LIANG1, Ji-gang PIAO1, 2, *, Hong-yue ZHENG3, Heng-wu XU4, Fan-zhu LI1, 2, *
Acta Pharmaceutica Sinica | 2021, 56(12) : 3243 - 3251
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Acta Pharmaceutica Sinica | 2021, 56(12): 3243-3251
• Special Reports Ⅰ: Anti-tumor Preparations of Traditional Chinese Medicine •
Preparation of mitochondrial targeted calcium arsenite/doxorubicin lipid nanoparticles and the in vitro study in reversing tumor drug resistance
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Ke ZHANG1, Tian-xiang YUE1, Meng-ying CHENG1, Zeng-ying LIANG1, Ji-gang PIAO1, 2, *, Hong-yue ZHENG3, Heng-wu XU4, Fan-zhu LI1, 2, *
Affiliations
  • 1. College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310000, China
  • 2. Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, Hangzhou 310000, China
  • 3. Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou 310000, China
  • 4. Department of Pharmacy, Jinhua People's Hospital, Jinhua 321000, China
Published: 2021-12-12 doi: 10.16438/j.0513-4870.2021-1169
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This study aims at the critical role of P-glycoprotein (P-gp) in tumor drug resistance, taking advantage of the adenosine triphosphate (ATP) dependence of P-gp mediated drug transport and efflux across the cell membrane. Mitochondrial targeted calcium arsenite/doxorubicin (DOX) lipid nanoparticles were constructed via hydrothermal method and thin-film dispersion method for reversing tumor drug resistance. The results showed that the lipid nanoparticles were uniform in size and well dispersed with a mean particle size of (261 ± 7) nm, zeta potential of (-9.6 ± 1.3) mV. The DOX loading efficiency and encapsulation efficiency were 22.6% and 84.0%. The in vitro drug release profile was pH-dependent; the drug accumulation at mitochondria was significantly increased, which then caused overload of calcium and inhibition of P-gp and ATP, thereby reversing tumor drug resistance. The simultaneously released arsenite ion and DOX could synergistically kill the tumor cells. In summary, the lipid nanoparticles prepared in this study have uniform particle size, high drug loading efficiency and encapsulation efficiency, excellent colloidal stability, pH responsiveness, and impressive ability to reverse tumor drug resistance, which may hold great potential in further clinical applications.

neoplasm  /  mitochondria  /  arsenic trioxide  /  lipid nanoparticle  /  drug resistance
Ke ZHANG, Tian-xiang YUE, Meng-ying CHENG, Zeng-ying LIANG, Ji-gang PIAO, Hong-yue ZHENG, Heng-wu XU, Fan-zhu LI. Preparation of mitochondrial targeted calcium arsenite/doxorubicin lipid nanoparticles and the in vitro study in reversing tumor drug resistance[J]. Acta Pharmaceutica Sinica, 2021 , 56 (12) : 3243 -3251 . DOI: 10.16438/j.0513-4870.2021-1169
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doi: 10.16438/j.0513-4870.2021-1169
  • Receive Date：2021-08-11
  • Online Date：2025-12-18
  • Published：2021-12-12
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History
  • Received：2021-08-11
  • Revised：2021-08-28
Affiliations
    1. College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310000, China
    2. Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, Hangzhou 310000, China
    3. Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou 310000, China
    4. Department of Pharmacy, Jinhua People's Hospital, Jinhua 321000, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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