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

Bo Dai, Xingyu Wu, Christopher J. Butch, Jianquan Wang, Ziyang Wang, Yisheng Wang, Shuming Nie, Qian Lu, Yiqing Wang, Yitao Ding

Research output: Contribution to journalArticle

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. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)1959-1966
Number of pages8
JournalNano Research
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2019

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Medical nanotechnology
Administrative data processing
Cytotoxins
Antibodies
Tumors
Dextran
Pharmaceutical Preparations
Liver
Polyethylene glycols
Animals
Nanoparticles
Adenosine Diphosphate
Molecules
Dextrans

Keywords

  • drug delivery
  • extremely potent drug
  • maytansinoid
  • nanomedicine
  • pH-sensitive nanocarrier

ASJC Scopus subject areas

  • Materials Science(all)
  • Electrical and Electronic Engineering

Cite this

Encapsulating maytansinoid in pH-sensitive nanocarriers : The importance of using extremely potent cytotoxic agents and fast release for nanomedicine to achieve tumor elimination. / Dai, Bo; Wu, Xingyu; Butch, Christopher J.; Wang, Jianquan; Wang, Ziyang; Wang, Yisheng; Nie, Shuming; Lu, Qian; Wang, Yiqing; Ding, Yitao.

In: Nano Research, Vol. 12, No. 8, 01.08.2019, p. 1959-1966.

Research output: Contribution to journalArticle

Dai, Bo ; Wu, Xingyu ; Butch, Christopher J. ; Wang, Jianquan ; Wang, Ziyang ; Wang, Yisheng ; Nie, Shuming ; Lu, Qian ; Wang, Yiqing ; Ding, Yitao. / Encapsulating maytansinoid in pH-sensitive nanocarriers : The importance of using extremely potent cytotoxic agents and fast release for nanomedicine to achieve tumor elimination. In: Nano Research. 2019 ; Vol. 12, No. 8. pp. 1959-1966.
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