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https://doi.org/10.1007/s12274-021-3867-0

Safety evaluation of nanodiamond-doxorubicin complexes in a Naïve Beagle canine model using hematologic, histological, and urine analysis

Liping Wang1,§, Wenqiong Su1,§, Khan Zara Ahmad1,§, Xin Wang1,§, Ting Zhang1, Youyi Yu1, Edward Kai-Hua Chow2,3,4,5,6 (✉), Dean Ho3,4,5,6 (✉), and Xianting Ding1 (✉)

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1 State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
2 Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
3 The N.1 Institute for Health (N.1), National University of Singapore, Singapore 117456, Singapore
4 The Institute for Digital Medicine (WisDM), National University of Singapore, Singapore 117456, Singapore
5 Department of Pharmacology, National University of Singapore, Singapore 117597, Singapore
6 Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Singapore
§ Liping Wang, Wenqiong Su, Khan Zara Ahmad, and Xin Wang contributed equally to this work.

Keywords: nanomedicine, doxorubicin, nanodiamonds, safety, biodistribution
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  • Abstract
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While doxorubicin (DOX) is one of the most common chemotherapeutic drugs for treating cancer, use of DOX must be managed carefully due to dose-related toxicity. Nanodiamond (ND) drug delivery system conjugated with DOX (NDX) has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models. In addition, extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates. Before the clinical translation of NDX, it is necessary to verify the safety of ND in large mammals. Studies of nanomedicine drug safety for large animal are not commonly reported, and this work represents a key milestone in bridging earlier advances towards clinical assessment. Herein, NDs’ safety as a drug-delivery platform was evaluated in Naïve Beagle dogs. The study is performed with DOX, ND, and NDX in a dual-gender animal model using intravenous (IV) injection and hepatic portal vein (HPV) injection methods. The dogs are monitored for their health phenotype changes in continuous 5 days. Blood and urine obtained are for clinical pathology research. The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model. This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.
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Safety evaluation of nanodiamond-doxorubicin complexes in a Naïve Beagle canine model using hematologic, histological, and urine analysis. Nano Res. https://doi.org/10.1007/s12274-021-3867-0

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