K. Zheng et al. Gold-nanoparticle-based multistage drug delivery system for antitumor therapy
Kaikai Zheng,
Dong Zhou,
Lili Wu,
Jian Li,
Bing Zhao,
Shihao Zhang,
Ruiying He,
Lan Xiao,
Iqbal Zoya,
Li Yu,
Yuhong Zhang,
Yulin Li,
Jie Gao,
Kaichun Li
Affiliations
Kaikai Zheng
Department of Oncology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Dong Zhou
Department of Oncology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Lili Wu
Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China
Jian Li
Department of Oncology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Bing Zhao
Department of Oncology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Shihao Zhang
Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, China
Ruiying He
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules of Ministry of Education, Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China
Lan Xiao
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove Campus, Brisbane, Queensland, Australia
Iqbal Zoya
Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, China
Li Yu
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules of Ministry of Education, Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China
Yuhong Zhang
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules of Ministry of Education, Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China
Yulin Li
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules of Ministry of Education, Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China
Jie Gao
Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China
Kaichun Li
Department of Oncology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, China
Nanoparticles can promote the accumulation of drugs in tumors. However, they find limited clinical applications because they cannot easily penetrate the stroma of cancer tissues, and it is difficult to control drug release. We developed a multiresponse multistage drug-delivery nanogel with improved tumor permeability and responsiveness to the tumor microenvironment for the controlled delivery of anticancer agents. For this purpose, ∼100 nm multistage drug delivery nanogels with pH, redox, near-infrared stimulation, and enzyme responsiveness were grown in situ using 20 nm gold nanoparticles (AuNPs) via an emulsion-aiding crosslinking technique with cysteine crosslinker. An alginate cysteine AuNP (ACA) nanocarrier can efficiently load the cationic drug doxorubicin (DOX) to produce a multistage drug delivery nanocarrier (DOX@ACA). DOX@ACA can maintain the slow release of DOX and reduce its toxicity. In cancer tissues, the high pH and reductase microenvironment combined with the in vitro delivery of alginate and near-infrared light drove drug release. The developed nanoparticles effectively inhibited cancer cells, and in vivo evaluations showed that they effectively enhanced antitumor activity while having negligible in vivo toxicity to major organs.
