DOX-loaded hydroxyapatite nanoclusters for colorectal cancer (CRC) chemotherapy: Evaluation based on the cancer cells and organoids

被引：6

作者：

Deng, Tianhao ^{[1
,2
]}

Luo, Dandan ^{[1
,2
,3
]}

Zhang, Rui ^{[1
,2
]}

Zhao, Ruibo ^{[1
,2
]}

Hu, Yeting ^{[4
]}

Zhao, Qingwei ^{[5
,6
]}

Wang, Shibo ^{[1
,2
]}

Iqbal, M. Zubair ^{[1
,2
]}

Kong, Xiangdong ^{[1
,2
]}

机构：

[1] Zhejiang Sci Tech Univ, Inst Smart Biomed Mat, Sch Mat Sci & Engn, Hangzhou 310018, Peoples R China

[2] Zhejiang Sci Tech Univ, Zhejiang Mauritius Joint Res Ctr Biomat & Tissue E, Hangzhou 310018, Peoples R China

[3] Zhejiang Sci Tech Univ, Sch Text Sci & Engn, Hangzhou 310018, Peoples R China

[4] Zhejiang Univ, Affiliated Hosp 2, Dept Colorectal Surg & Oncol, Key Lab Canc Prevent & Intervent,Minist Educ,Sch, Hangzhou 310000, Peoples R China

[5] Zhejiang Univ, Res Ctr Clin Pharm, Sch Med, Hangzhou 310018, Peoples R China

[6] Zhejiang Univ, Affiliated Hosp 1, Key Lab Drug Evaluat & Clin Res Zhejiang Prov, Sch Med, Hangzhou 310018, Peoples R China

来源：

SLAS TECHNOLOGY | 2023年 / 28卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Organoids; Hydroxyapatite nanoclusters; Colorectal cancer; Nanocarriers; Chemotherapy; TUMOR-THERAPY; IN-VITRO; NANOPARTICLES; NEPHROTOXICITY; DOXORUBICIN; RELEASE; AGENT; LIVER;

D O I：

10.1016/j.slast.2022.10.002

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

It is meaningful to find suitable in vitro models for preclinical toxicology and efficacy evaluation of nanodrugs and nanocarriers or drug screening and promoting clinical transformation of nanocarriers. The emergence and development of organoids technology provide a great possibility to achieve this goal. Herein, we constructed an in vitro 3D organoid model to study the inhibitory effect of nanocarriers on colorectal cancer. And designed hydroxyapatite nanoclusters (c-HAP) mediated by polydopamine (PDA) formed under alkaline conditions (pH 9.0), then used c-HAP to load DOX (c-HAP/DOX) as nanocarrier for improved chemotherapy. In vitro , drug release experiments show that c-HAP/DOX has suitable responsive to pH, can be triggered to the facile release of DOX in a slightly acidic environment (pH 6.0), and maintain specific stability in a neutral pH value (7.4) environment. c-HAP/DOX showed an excellent antitumor effect in the two-dimensional (2D) cell model and three-dimensional (3D) patient-derived colon cancer organoids (PDCCOs) model. In addition, c-HAP/DOX can release a sufficient amount of DOX to produce cytotoxicity in a slightly acidic environment, entering efficiently into the colorectal cancer cells caused endocytosis and induced apoptosis. Therefore, organoids can serve as an effective in vitro model to present the structure and function of colorectal cancer tissues and be used to evaluate the efficacy of nanocarriers for tumors.

引用

页码：22 / 31

页数：10