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DOI: 10.1055/a-2548-5404
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Small Molecules in Medicinal Chemistry

Exploring the Dual Therapeutic Potential of a Photoactivatable AIEgen in Cancer and Alzheimer’s Disease

Priyam Ghosh
a   Department of Chemistry, Indian Institute of Technology Guwahati, Assam 781039, India
,
Sayantani Mukhopadhyay
b   Center for Nanotechnology, Indian Institute of Technology Guwahati, Assam 781039, India
,
Mrinalini Singh
a   Department of Chemistry, Indian Institute of Technology Guwahati, Assam 781039, India
,
Siddhartha Sankar Ghosh
b   Center for Nanotechnology, Indian Institute of Technology Guwahati, Assam 781039, India
c   Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Assam 781039, India
d   Department of Bioscience and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
,
Parameswar Krishnan Iyer∗
a   Department of Chemistry, Indian Institute of Technology Guwahati, Assam 781039, India
b   Center for Nanotechnology, Indian Institute of Technology Guwahati, Assam 781039, India
c   Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Assam 781039, India
› Author AffiliationsThe authors acknowledge the financial grants from the Department of Science and Technology (DST), New Delhi, India (projects DST/CRG/2019/002614 and FIST:SR/FST/CS-II/2017/23C), the Department of Electronics and Information Technology, Ministry of Communications and Information Technology (Deity), India (No. 5(1)/2022-NANO), the Indian Council of Medical Research (ICMR) (no. 5/3/8/20/2019-ITR), and the Max-Planck-Gesellschaft (IGSTC/MPG/PG(PKI)/2011A/48). P.G. acknowledges Prime Minister's Research Fellowship (Fellowship No. 1900819), Ministry of Education, India for funding his research.
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Abstract

One minimally invasive treatment that may help with Alzheimer’s disease (AD) and cancer is photodynamic therapy (PDT). Side effects are reduced with PDT, which targets cancer cells while preserving healthy tissue. Photo-oxygenation of amyloid-β (Aβ) is considered an efficient way to inhibit Aβ aggregation in AD. In this work, we constructed a photoactivatable aggregation-induced emission probe, 2-(7a-ethoxybenzo[f]indeno[1,2-b]chromen-12(7aH)-ylidene)malononitrile (P1), which exhibited red emission, amyloid targeting ability, good biocompatibility, and photostability, and a remarkable capacity to generate reactive oxygen species. Molecular docking was performed to elucidate the interactions between P1 with Aβ40 and Cathepsin D, confirming its binding efficacy and stability. In vitro studies confirm the therapeutic ability of the probe in PDT. These combined properties highlight the comprehensive dual therapeutic potential of P1 in AD and cancer.

Key words

AIEgen - multifunctional fluorescent probe - reactive oxygen species - cancer photodynamic therapy - Alzheimer’s disease

Supporting Information



Publication History

Received: 31 December 2024

Accepted after revision: 27 February 2025

Accepted Manuscript online:
28 February 2025

Article published online:
09 April 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
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