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Title: Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties
Authors: Wu, Zhuoran
Lim, Hong Kit
Tan, Shao Jie
Gautam, Archana
Hou, Han Wei
Ng, Kee Woei
Tan, Nguan Soon
Tay, Chor Yong
Keywords: Science::Medicine
Issue Date: 2020
Source: Wu, Z., Lim, H. K., Tan, S. J., Gautam, A., Hou, H. W., Ng, K. W., Tan, N. S. & Tay, C. Y. (2020). Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties. Small, 16(34), 2003757-.
Project: NTU-HSPH 18002 to C.Y.T.
Journal: Small
Abstract: Exogenous sources of amino acids are essential nutrients to fuel cancer growth. Here, the increased demand for amino acid displayed by cancer cells is unconventionally exploited as a design principle to replete cancer cells with apoptosis inducing nanoscopic porous amino acid mimics (Nano-PAAM). A small library consisting of nine essential amino acids nanoconjugates (30 nm) are synthesized, and the in vitro anticancer activity is evaluated. Among the Nano-PAAMs, l-phenylalanine functionalized Nano-PAAM (Nano-pPAAM) has emerged as a novel nanotherapeutics with excellent intrinsic anticancer and cancer-selective properties. The therapeutic efficacy of Nano-pPAAM against a panel of human breast, gastric, and skin cancer cells could be ascribed to the specific targeting of the overexpressed human large neutral amino acid transporter SLC7A5 (LAT-1) in cancer cells, and its intracellular reactive oxygen species (ROS) inducing properties of the nanoporous core. At the mechanistic level, it is revealed that Nano-pPAAM could activate both the extrinsic and intrinsic apoptosis pathways to exert a potent "double-whammy" anticancer effect. The potential clinical utility of Nano-pPAAM is further investigated using an MDA-MB-231 xenograft in NOD scid gamma mice, where an overall suppression of tumor growth by 60% is achieved without the aid of any drugs or application of external stimuli.
ISSN: 1613-6829
DOI: 10.1002/smll.202003757
DOI (Related Dataset): 10.21979/N9/UNQAHC
Schools: School of Materials Science and Engineering 
School of Mechanical and Aerospace Engineering 
School of Biological Sciences 
Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: Skin Research Institute of Singapore
Research Centres: Environmental Chemistry and Materials Centre
Nanyang Environment and Water Research Institute 
Rights: © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:LKCMedicine Journal Articles
MAE Journal Articles
MSE Journal Articles
SBS Journal Articles

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