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

doi:10.1016/j.nano.2020.102283

HFCAS OpenIR

	An ultra-long circulating nanoparticle for reviving a highly selective BCR-ABL inhibitor in long-term effective and safe treatment of chronic myeloid leukemia
	Fu, Liyi 1; Zou, Fengming 1; Liu, Qingwang 2; Wang, Beilei 1,3; Wang, Junqing 4,5,6; Liang, Huamin 2; Liang, Xiaofei 1; Liu, Jing 1; Shi, Jinjun 5,6; Liu, Qingsong1,2,7
	2020-10-01
发表期刊	NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
ISSN	1549-9634
通讯作者	Liu, Jing(jliu@hmfl.ac.cn) ; Shi, Jinjun(jshi@bwh.harvard.edu) ; Liu, Qingsong(qsliu97@hmfl.ac.cn)
摘要	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. (C) 2020 Elsevier Inc. All rights reserved.
关键词	Chronic myeloid leukemia BCR-ABL Long-circulating nanoparticle Drug delivery
DOI	10.1016/j.nano.2020.102283
关键词[WOS]	DRUG-DELIVERY ; SCHIFFS BASE ; CO-DELIVERY ; IMATINIB ; BIODISTRIBUTION ; DOXORUBICIN ; MECHANISMS ; NILOTINIB ; PRODRUG ; DISEASE
收录类别	SCI
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDA09030301] ; Natural Science Foundation of Anhui Province[1808085QH260] ; Natural Science Foundation of Anhui Province[1808085MH268] ; Frontier Science Key Research Program of CAS[GrantQYZDB-SSW-SLH037] ; CASHIPS Director's Fund[BJPY2019A03] ; Key Program of 13th five-year plan of CASHIPS[KP-201726] ; Hefei leading talent ; Youth Innovation Promotion Association[2016385]
项目资助者	Strategic Priority Research Program of the Chinese Academy of Sciences ; Natural Science Foundation of Anhui Province ; Frontier Science Key Research Program of CAS ; CASHIPS Director's Fund ; Key Program of 13th five-year plan of CASHIPS ; Hefei leading talent ; Youth Innovation Promotion Association
WOS研究方向	Science & Technology - Other Topics ; Research & Experimental Medicine
WOS类目	Nanoscience & Nanotechnology ; Medicine, Research & Experimental
WOS记录号	WOS:000573096200005
出版者	ELSEVIER
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/104348
专题	中国科学院合肥物质科学研究院
通讯作者	Liu, Jing; Shi, Jinjun; Liu, Qingsong
作者单位	1.Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei, Anhui, Peoples R China 2.Chinese Acad Sci, Inst Technol Innovat, Hefei Inst Phys Sci, Hefei, Anhui, Peoples R China 3.Univ Sci & Technol China, Hefei, Anhui, Peoples R China 4.Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Guangzhou, Guangdong, Peoples R China 5.Harvard Med Sch, Ctr Nanomed, Brigham & Womens Hosp, Boston, MA 02115 USA 6.Harvard Med Sch, Dept Anesthesiol, Brigham & Womens Hosp, Boston, MA 02115 USA 7.Anhui Univ, Inst Phys Sci & Informat Technol, Key Lab Struct & Funct Regulat Hybrid Mat, Minist Educ, Hefei, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Fu, Liyi,Zou, Fengming,Liu, Qingwang,et al. An ultra-long circulating nanoparticle for reviving a highly selective BCR-ABL inhibitor in long-term effective and safe treatment of chronic myeloid leukemia[J]. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE,2020,29.
APA	Fu, Liyi.,Zou, Fengming.,Liu, Qingwang.,Wang, Beilei.,Wang, Junqing.,...&Liu, Qingsong.(2020).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,29.
MLA	Fu, Liyi,et al."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 29(2020).