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

Abstract

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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Acknowledgements

The work is partially funded by the National Natural Science Foundation of China (No. 81871448), the National Key Research and Development Program of China (Nos. 2017YFC0107603 and 2017ZX10203205-006-002), and the Medical-Engineering Cross Foundation of Shanghai Jiao Tong University (Nos. YG2017QN52, ZH2018QNA54, and ZH2018QNA49).

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Correspondence to Edward Kai-Hua Chow, Dean Ho or Xianting Ding.

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

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Wang, L., Su, W., Ahmad, K.Z. et al. Safety evaluation of nanodiamond-doxorubicin complexes in a Naïve Beagle canine model using hematologic, histological, and urine analysis. Nano Res. (2021). https://doi.org/10.1007/s12274-021-3867-0

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Keywords

  • nanomedicine
  • doxorubicin
  • nanodiamonds
  • safety
  • biodistribution