TY - JOUR
T1 - Encapsulating maytansinoid in pH-sensitive nanocarriers
T2 - The importance of using extremely potent cytotoxic agents and fast release for nanomedicine to achieve tumor elimination
AU - Dai, Bo
AU - Wu, Xingyu
AU - Butch, Christopher J.
AU - Wang, Jianquan
AU - Wang, Ziyang
AU - Wang, Yisheng
AU - Nie, Shuming
AU - Lu, Qian
AU - Wang, Yiqing
AU - Ding, Yitao
N1 - Publisher Copyright:
© 2019, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.].
AB - 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.].
KW - drug delivery
KW - extremely potent drug
KW - maytansinoid
KW - nanomedicine
KW - pH-sensitive nanocarrier
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U2 - 10.1007/s12274-019-2464-y
DO - 10.1007/s12274-019-2464-y
M3 - Article
AN - SCOPUS:85068312287
SN - 1998-0124
VL - 12
SP - 1959
EP - 1966
JO - Nano Research
JF - Nano Research
IS - 8
ER -