An ultra-long circulating nanoparticle for reviving a highly selective BCR-ABL inhibitor in long-term effective and safe treatment of chronic myeloid leukemia.

Liyi Fu, Fengming Zou, Qingwang Liu, Beilei Wang, Junqing Wang, Huamin Liang, Xiaofei Liang, Jing Liu, Jinjun Shi, Qingsong Liu

Nanomedicine : nanotechnology, biology, and medicine 2020 Oct

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Nanotechnology has demonstrated great promise for the development of more effective and safer cancer therapies. We recently developed a highly selective inhibitor of BCR-ABL fusion tyrosine kinase for chronic myeloid leukemia (CML). However, the poor drug-like properties were hurdles to its further clinical development. Herein, we re-investigate it by conjugating an amphiphilic polymer and self-assembling into a nanoparticle (NP) with a high loading (~10.3%). The formulation greatly improved its solubility and drastically extended its circulation half-life from ~5.3 to ~117 h (>20-fold). In the 150 days long-term engraftment model experiment, long intravenous dosing intervals of the NPs (every 4 or 8 days) exhibited much better survival and negligible toxicities as compared to daily oral administration of the inhibitor. Moreover, the NPs showed excellent inhibition of tumor growth in the subcutaneous xenograft model. All results suggest that the ultra-long circulating pro-drug NP may provide an effective and safe therapeutic strategy for BCR-ABL-positive CML. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Liyi Fu, Fengming Zou, Qingwang Liu, Beilei Wang, Junqing Wang, Huamin Liang, Xiaofei Liang, Jing Liu, Jinjun Shi, Qingsong Liu. An ultra-long circulating nanoparticle for reviving a highly selective BCR-ABL inhibitor in long-term effective and safe treatment of chronic myeloid leukemia. Nanomedicine : nanotechnology, biology, and medicine. 2020 Oct;29:102283