Theranostics 2020; 10(10):4349-4358. doi:10.7150/thno.43402 This issue Cite

Research Paper

Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy

Fang Xu1*, Jianzhi Zhu1,3*, Lizhou Lin2*, Changchang Zhang1, Wenjie Sun1, Yu Fan1, Fangfang Yin4, Jan C. M. van Hest3, Han Wang4, Lianfang Du2✉, Xiangyang Shi1✉

1. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-dimension Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
2. Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China.
3. Bio-Organic Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands.
4. Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China.
*Authors contributed equally to this work.

Citation:
Xu F, Zhu J, Lin L, Zhang C, Sun W, Fan Y, Yin F, van Hest JCM, Wang H, Du L, Shi X. Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy. Theranostics 2020; 10(10):4349-4358. doi:10.7150/thno.43402. https://www.thno.org/v10p4349.htm
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Abstract

Graphic abstract

Development of versatile nanoplatforms that simultaneously integrate therapeutic and diagnostic features for stimuli-responsive delivery to tumors remains a great challenge. In this work, we report a novel intelligent redox-responsive hybrid nanosystem composed of MnO2 nanoparticles (NPs) and doxorubicin (DOX) co-loaded within poly(N-vinylcaprolactam) nanogels (PVCL NGs) for magnetic resonance (MR) imaging-guided and ultrasound-targeted microbubble destruction (UTMD)-promoted tumor chemotherapy.

Methods: PVCL NGs were first synthesized via a precipitation polymerization method, decorated with amines using ethylenediamine, and loaded with MnO2 NPs through oxidation with permanganate and DOX via physical encapsulation and Mn-N coordination bonding. The as-prepared DOX/MnO2@PVCL NGs were well characterized. UTMD-promoted cellular uptake and therapeutic efficacy of the hybrid NGs were assessed in vitro, and a xenografted tumor model was used to test the NGs for MR imaging and UTMD-promoted tumor therapy in vivo.

Results: The as-prepared DOX/MnO2@PVCL NGs with a size of 106.8 nm display excellent colloidal stability, favorable biocompatibility, and redox-responsiveness to the reductive intracellular environment and tumor tissues having a relatively high glutathione (GSH) concentration that can trigger the synchronous release of Mn2+ for enhanced T1-weighted MR imaging and DOX for enhanced cancer chemotherapy. Moreover, the DOX/MnO2@PVCL NGs upon the UTMD-promotion exhibit a significantly enhanced tumor growth inhibition effect toward subcutaneous B16 melanoma owing to the UTMD-improved cellular internalization and tumor penetration.

Conclusion: Our work thereby proposes a promising theranostic nanoplatform for stimuli-responsive T1-weighted MR imaging-guided tumor chemotherapy.

Keywords: nanogels, manganese dioxide nanoparticles, ultrasound-targeted microbubble destruction, magnetic resonance imaging, chemotherapy


Citation styles

APA
Xu, F., Zhu, J., Lin, L., Zhang, C., Sun, W., Fan, Y., Yin, F., van Hest, J.C.M., Wang, H., Du, L., Shi, X. (2020). Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy. Theranostics, 10(10), 4349-4358. https://doi.org/10.7150/thno.43402.

ACS
Xu, F.; Zhu, J.; Lin, L.; Zhang, C.; Sun, W.; Fan, Y.; Yin, F.; van Hest, J.C.M.; Wang, H.; Du, L.; Shi, X. Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy. Theranostics 2020, 10 (10), 4349-4358. DOI: 10.7150/thno.43402.

NLM
Xu F, Zhu J, Lin L, Zhang C, Sun W, Fan Y, Yin F, van Hest JCM, Wang H, Du L, Shi X. Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy. Theranostics 2020; 10(10):4349-4358. doi:10.7150/thno.43402. https://www.thno.org/v10p4349.htm

CSE
Xu F, Zhu J, Lin L, Zhang C, Sun W, Fan Y, Yin F, van Hest JCM, Wang H, Du L, Shi X. 2020. Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy. Theranostics. 10(10):4349-4358.

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