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Research Article

Encapsulating maytansinoid in pH-sensitive nanocarriers: The importance of using extremely potent cytotoxic agents and fast release for nanomedicine to achieve tumor elimination

Bo Dai1,§, Xingyu Wu1,§, Christopher J. Butch2,§, Jianquan Wang2, Ziyang Wang2, Yisheng Wang2, Shuming Nie2,3, Qian Lu2( ), Yiqing Wang2( ), Yitao Ding1( )
Drum Tower Clinical Medical College,Nanjing Medical University,Nanjing,210008,China;
Department of Biomedical Engineering,College of Engineering and Applied Sciences, Nanjing University,Nanjing,210008,China;
Department of Biomedical Engineering,University of Illinois at Urbana-Champaign,Illinois,61801,USA;

§ Bo Dai, Xingyu Wu, and Christopher J. Butch contributed equally to this work.

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Abstract

The clinical translation of nanomedicine is hindered by the low delivery efficiency, and consequently drug concentration in tumor sites falls short of the therapeutic effective range which leads to poor clinical outcomes. One important lesson learned from the development of antibody-drug-conjugates (ADCs) is that to achieve significant clinical benefits, extremely potent cytotoxic agents and cleavable linkers should be used. By encapsulating maytansinoid, AP3, which is 100–1, 000 times more potent than most conventional small molecule anticancer drugs, in pH-sensitive acetalated dextran-polyethylene glycol (PEG) (ADP) nanocarriers, even with only 1% drug loading, we were able to eradicate tumors in 50% of tested animals with negligible side effects, while free AP3 only showed marginal efficacy and severe liver damages. This study suggests that besides improving the low efficiency of nano-delivery systems, the potency of drug to be delivered is also critical to the clinical outcomes of nanomedicine. Our results also showed that ADP nanoparticles (NPs) were able to expand the narrow therapeutic window of maytansinoids in a similar manner to the ADCs.

Keywords

nanomedicinedrug deliverymaytansinoidextremely potent drugpH-sensitive nanocarrier

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Nano Research
Volume 12 Issue 8,
August 2019
Pages 1959-1966
DOI: 10.1007/s12274-019-2464-y
Cite this article:
Dai B, Wu X, Butch CJ, et al. Encapsulating maytansinoid in pH-sensitive nanocarriers: The importance of using extremely potent cytotoxic agents and fast release for nanomedicine to achieve tumor elimination. Nano Research, 2019, 12(8): 1959-1966. https://doi.org/10.1007/s12274-019-2464-y
Topics:
Controlled drug deliveryDrug deliveryDrug interactionsMedical nanotechnologypH sensorsTumors

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Received: 01 March 2019
Revised: 15 May 2019
Accepted: 17 June 2019
Published: 27 June 2019
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
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