Two-Dimensional Ultra-Thin Nanosheets with Extraordinarily High Drug Loading and Long Blood Circulation for Cancer Therapy

作者全名："Zhang, He; Zhang, Liang; Cao, Zhenbang; Cheong, Soshan; Boyer, Cyrille; Wang, Zhigang; Yun, Sung Lai Jimmy; Amal, Rose; Gu, Zi"

作者地址："[Zhang, He; Cao, Zhenbang; Boyer, Cyrille; Amal, Rose; Gu, Zi] Univ New South Wales, Sch Chem Engn, Sydney, NSW 2052, Australia; [Boyer, Cyrille; Gu, Zi] Univ New South Wales, Australian Ctr NanoMed ACN, Sydney, NSW 2052, Australia; [Zhang, Liang; Wang, Zhigang] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Cheong, Soshan] Univ New South Wales, Electron Microscope Unit, Sydney, NSW 2052, Australia; [Yun, Sung Lai Jimmy] Qingdao Int Academician Pk Res Inst, Qingdao 266000, Shandong, Peoples R China"

通信作者："Gu, Z (通讯作者)，Univ New South Wales, Sch Chem Engn, Sydney, NSW 2052, Australia.; Gu, Z (通讯作者)，Univ New South Wales, Australian Ctr NanoMed ACN, Sydney, NSW 2052, Australia.; Wang, ZG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China."

来源：SMALL

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000791440900001

JCR分区：Q1

影响因子：13.3

年份：2022

卷号：18

期号：22

开始页：　

结束页：　

文献类型：Article

关键词：2D nanomaterials; cancer therapy; drug delivery; layered double hydroxides; nanomedicine

摘要："Nanoparticle drug delivery is largely restricted by the low drug loading capacity of nanoparticle carriers. To address this critical challenge and maximize the potential of nanoparticle drug delivery, a 2D ultra-thin layered double hydroxide (LDH) nanosheet with exceptionally high drug loading, excellent colloidal stability, and prolonged blood circulation for cancer treatment is constructed. The nanosheet is synthesized via a biocompatible polymer-assisted bottom-up method and exhibits an ultra-thin 2D sheet-like structure that enables a considerable amount of cargo anchoring sites available for drug loading, leading to an extraordinary 734% (doxorubicin/nanoparticle mass ratio) drug loading capacity. Doxorubicin delivered by the nanosheet remains stable on the nanosheet carrier under the physiological pH condition, while showing sustained release in the tumor microenvironment and the intracellular environment, thus demonstrating on-demand drug release as a result of pH-responsive biodegradation of nanosheets. Using in vitro and in vivo 4T1 breast cancer models, the nanosheet-based ultra-high drug-loading system demonstrates even enhanced therapeutic performance compared to the multilayered LDH-based high drug-loading system, in terms of increased cellular uptake efficiency, prolonged blood circulation, superior therapeutic effect, and reduced systemic toxicity."

基金机构：ARC; National Health and Medical Research Council of Australia (NHMRC) Early Career Fellowship; Key Project of Application Development Plan of Chongqing [cstc2019jscx-dxwtBX0004]; Chinese Scholarship Council; University of New South Wales Engineering Faculty Research Fund

基金资助正文："H.Z. and L.Z. contributed equally to this work. This work was financially supported by ARC Discovery Projects, the National Health and Medical Research Council of Australia (NHMRC) Early Career Fellowship, University of New South Wales Engineering Faculty Research Fund, and Key Project of Application Development Plan of Chongqing (cstc2019jscx-dxwtBX0004). H.Z. acknowledges the financial support from the Chinese Scholarship Council. The authors acknowledge the use of facilities in the Electron Microscope Unit and Microscopy Australia, Solid State & Elemental Analysis Unit, Spectroscopy Laboratory, NMR Facility, Biomedical Imaging Facility within the Mark Wainwright Analytical Centre (MWAC) at UNSW Sydney."