A small-molecule self-assembled nanodrug for combination therapy of photothermal-differentiation-chemotherapy of breast cancer stem cells

Xie，Xin1; Jiang，Kailong2; Li，Bowen3; Hou，Shenglei2; Tang，Honglin3; Shao，Baihao3; Ping，Yuan3; Zhang，Qiqing1

2022-07-01

10.1016/j.biomaterials.2022.121598

BIOMATERIALS   影响因子和分区

0142-9612

1878-5905

The combination therapy with different treatment modalities has been widely applied in the clinical applications of cancer treatment. However, it stills a considerable challenge to achieve co-delivery of different drugs because of distinct drug encapsulation mechanisms, low drug loading, and high excipient-related toxicity. Cancer stem cells (CSCs) are closely related to tumor metastasis and recurrence due to high chemoresistance. Herein, we report a stimuli-responsive and tumor-targeted small-molecule self-assembled nanodrug for the combination therapy against CSCs and normal cancer cells. The hydrophobic differentiation-inducing agent (all-trans retinoic acid, ATRA) and hydrophilic anticancer drug (irinotecan, IRI) constitute this amphiphilic nanodrug, which could self-assemble into stable nanoparticles and encapsulate the photothermal agent IR825. Upon cellular uptake, this nanodrug display good release profiles in response to acid and esterase microenvironments by ester linkage. The released drugs not only increase chemotherapy sensitivity by the differentiation of CSCs into non-CSCs, but also exhibit superior cytotoxicity in cancer cells. In addition, IR825 within this nanodrug enables in vivo fluorescence/photoacoustic (PA) imaging allowing for tracking drug distribution. Moreover, the DSPE-PEG-RGD-functionalized nanodrug displayed high tumor accumulation and good biocompatibility, enabling efficient inhibition of tumor growth and tumor metastasis in tumor-bearing mice.

Breast cancer Cancer stem cells Combination therapy Nanodrug Small-molecule self-assemble

SCI ; EI

英语

第一 ; 通讯

Basic and Applied Basic Research Foundation of Guangdong Province[2020B1515120091];China Postdoctoral Science Foundation[2021M691440];National Natural Science Foundation of China[32000992];National Natural Science Foundation of China[32101129];National Natural Science Foundation of China[JCYJ20210324113006017];

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000815029200002

ELSEVIER SCI LTD

20222312189777

Biocompatibility ; Controlled drug delivery ; Cytology ; Diseases ; Drug products ; Esters ; Mammals ; Molecules ; Pathology ; Stem cells ; Targeted drug delivery ; Tumors

Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6 ; Biology:461.9 ; Immunology:461.9.1 ; Organic Compounds:804.1 ; Atomic and Molecular Physics:931.3

MATERIALS SCIENCE

2-s2.0-85131143622

Scopus

1.Institute of Biomedical Engineering,The First Affiliated Hospital (Shenzhen People's Hospital),Southern University of Science and Technology,Shenzhen,518055,China
2.Institute of Biomedical Engineering,The Second Clinical Medical College,Jinan University (Shenzhen People's Hospital),Shenzhen,518020,China
3.College of Pharmaceutical Sciences,Zhejiang University,Hangzhou,China

Xie，Xin,Jiang，Kailong,Li，Bowen,et al. A small-molecule self-assembled nanodrug for combination therapy of photothermal-differentiation-chemotherapy of breast cancer stem cells[J]. BIOMATERIALS,2022,286.

Xie，Xin.,Jiang，Kailong.,Li，Bowen.,Hou，Shenglei.,Tang，Honglin.,...&Zhang，Qiqing.(2022).A small-molecule self-assembled nanodrug for combination therapy of photothermal-differentiation-chemotherapy of breast cancer stem cells.BIOMATERIALS,286.

Xie，Xin,et al."A small-molecule self-assembled nanodrug for combination therapy of photothermal-differentiation-chemotherapy of breast cancer stem cells".BIOMATERIALS 286(2022).