title: Stimulative nanogels with enhanced thermosensitivity for therapeutic delivery via β-cyclodextrin-induced formation of inclusion complexes.
abstract: To explore the potential biomedical application of thermoresponsive nanosystems, it is important to enhance their thermosensitivity to improve the controllability in delivery of therapeutic agents. The present work develops multifunctional nanogels with enhanced thermosensitivity through copolymerization of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) in the presence of β-cyclodextrin (β-CD), using N,N'-bis(acryloyl)cystamine (BAC) as a biodegradable crosslinker. The resulting nanogels display significantly improved sensitivity in deswelling (swelling) behavior upon temperature increase (decrease) around body temperature. The nanogels can effectively encapsulate doxorubicin (DOX), which can be released in an accelerated way under microenvironments that mimic intracellular reductive conditions and acidic tumor tissues. Release can also be remotely manipulated by increasing temperature. In vitro study indicates that the nanogels are quickly taken up by KB cells (a human epithelial carcinoma cell line), exerting improved anticancer cytotoxicity, showing their potential for delivery of therapeutic agents beyond anticancer drugs.
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Yi
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, 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 200237, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, 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 200237, China.
authors.forename: Shihao
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
authors.forename: Zhengguang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China; The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, 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 200237, China; CQM - Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal. Electronic address: yulinli@uma.pt.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China. Electronic address: peixinhe@aliyun.com.
authors.forename: Peixin
authors.initials: P
authors.lastname: He
keywords: Anticancer cytotoxicity; Enhanced thermosensitivity; Nanogels; Poly(N-isopropylacrylamide); β-Cyclodextrin