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Multidrug-resistance (MDR) featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic. Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR. However, the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites. In the present study, a type of self-targeting hyaluronate (HA) nanogels (CDDPHANG/DOX) to reverse drug resistance through the synchronized pharmacokinetics, intratumoral distribution, and intracellular release of topoisomerase II inhibitor doxorubicin (DOX) and DNA- crosslinking agent cisplatin (CDDP) is developed. With prolonged circulation time and enhanced intratumoral accumulation in vivo , CDDPHANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity. Besides, fluorescence imaging of DOX combined with the micro-computed tomography (micro-CT) imaging of CDDP facilitates the visualization of this combination tumor chemotherapy. With visualizable synchronized drug delivery, the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.

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Publication history

Received: 19 July 2020
Revised: 09 September 2020
Accepted: 12 September 2020
Published: 01 March 2021
Issue date: March 2021

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© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature

Acknowledgements

This study was financially supported by the National Key Research and Development Program of China (No. 2016YFC1100701), the National Natural Science Foundation of China (Nos. 52022095, 51973216, and 51873207), the Science and Technology Development Program of Jilin Province (No. 20200404182YY), and the Youth Innovation Promotion Association of Chinese Academy of Sciences (No. 2019005). Y. S. Z. did not receive any of these funding nor was he paid in any form; instead, support by the Brigham Research Institute is acknowledged.

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Email: nanores@tup.tsinghua.edu.cn

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