Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties
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 s...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/155259 |
| _version_ | 1826112938051633152 |
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| author | Wu, Zhuoran Lim, Hong Kit Tan, Shao Jie Gautam, Archana Hou, Han Wei Ng, Kee Woei Tan, Nguan Soon Tay, Chor Yong |
| author2 | School of Materials Science and Engineering |
| author_facet | School of Materials Science and Engineering Wu, Zhuoran Lim, Hong Kit Tan, Shao Jie Gautam, Archana Hou, Han Wei Ng, Kee Woei Tan, Nguan Soon Tay, Chor Yong |
| author_sort | Wu, Zhuoran |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:15:20Z |
| format | Journal Article |
| id | ntu-10356/155259 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:15:20Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1552592023-07-31T08:48:11Z Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties Wu, Zhuoran Lim, Hong Kit Tan, Shao Jie Gautam, Archana Hou, Han Wei Ng, Kee Woei Tan, Nguan Soon Tay, Chor Yong School of Materials Science and Engineering School of Mechanical and Aerospace Engineering School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Skin Research Institute of Singapore Environmental Chemistry and Materials Centre Nanyang Environment and Water Research Institute Science::Medicine Engineering::Materials Cancer Targeting Large Neutral Amino Acid Transporter 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. Nanyang Technological University The authors gratefully acknowledge the financial support from the Nanyang Technological University NTU-Harvard School of Public Health Initiative for Sustainable Nanotechnology (NTU-Harvard SusNano) Program (NTU-HSPH 18002 to C.Y.T.). 2022-03-03T08:46:03Z 2022-03-03T08:46:03Z 2020 Journal Article 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-. https://dx.doi.org/10.1002/smll.202003757 1613-6829 https://hdl.handle.net/10356/155259 10.1002/smll.202003757 32686344 2-s2.0-85088121541 34 16 2003757 en NTU-HSPH 18002 to C.Y.T. Small 10.21979/N9/UNQAHC © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. All rights reserved. |
| spellingShingle | Science::Medicine Engineering::Materials Cancer Targeting Large Neutral Amino Acid Transporter Wu, Zhuoran Lim, Hong Kit Tan, Shao Jie Gautam, Archana Hou, Han Wei Ng, Kee Woei Tan, Nguan Soon Tay, Chor Yong Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties |
| title | Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties |
| title_full | Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties |
| title_fullStr | Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties |
| title_full_unstemmed | Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties |
| title_short | Potent-by-design : amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties |
| title_sort | potent by design amino acids mimicking porous nanotherapeutics with intrinsic anticancer targeting properties |
| topic | Science::Medicine Engineering::Materials Cancer Targeting Large Neutral Amino Acid Transporter |
| url | https://hdl.handle.net/10356/155259 |
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