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A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver

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Abstract

Although nanotechnology has been rapidly developed and applied in tumor targeting, the outcome of chemotherapy remains greatly restricted by the toxicity of cytotoxic drugs in normal tissues and cells. Therefore, the development of alternative delivery systems, with few side effects in normal cells, has attracted increasing attention. Energy restriction is a novel and promising approach to cancer treatment, which can restrict tumor growth via inhibition of cellular energy metabolism. In this study, a novel tumor targeting system, based on folate-conjugated bovine serum albumin (BSA), was developed to co-deliver albendazole and nanosilver simultaneously, to restrain the energy metabolism of tumor cells. This nanosystem showed stronger anti-tumor efficacy than those using nanoparticles without folic acid modification, nanosilver, or albendazole, both in vitro and in vivo. This nanosystem depleted cellular ATP via direct inhibition of glycolytic enzymes and mitochondrial damage, resulting in inhibition of proliferation, cell-cycle arrest, and apoptosis of tumor cells. The enhanced anti-tumor activity contributed to the tumor-targeting ability of this system, resulting in specific energy inhibition in tumor cells. Toxicity evaluation was performed to confirm the safety of this system. This nanosystem provides an efficient and safe strategy for tumor therapy.

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Acknowledgements

We are thankful for financial support from the National Natural Science Foundation of China (Nos. 81690263 and 81361140344), the National Basic Research Program of China (No. 2013CB932500) and the Development Project of Shanghai Peak Disciplines–Integrated Medicine (No. 20150407).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, China

    Jianming Liang, Ruixiang Li, Yuwei He, Jing Qin & Jianxin Wang

  2. Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China

    Qi Wang

  3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd., Shanghai, 201203, China

    Yongzhuo Huang

  4. Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Rd., Shanghai, 201203, China

    Jianming Liang & Weigen Lu

  5. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No1166, Liu Tai Avenue, Wenjiang District, Chengdu, 610072, China

    Chengli Ling

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Liang, J., Li, R., He, Y. et al. A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver. Nano Res. 11, 4507–4523 (2018). https://doi.org/10.1007/s12274-018-2032-x

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