A research team led by Zhao Qi, associate professor in the Faculty of Health Sciences (FHS) at the University of Macau (UM), and a team led by Shen Qingming, professor in the School of Telecommunication and Information Engineering at the Nanjing University of Posts and Telecommunications, have made significant progress in developing a tumour microenvironment (TME) activated phototheranostic nanoplatform in the second near-infrared window (NIR-II, 1000-1700nm). They succeeded in fabricating a TME-activated nanoprobe through a simple coordination-driven self-assembly strategy, which can achieve sensitive and specific tumour diagnosis and the synergistic anti-tumour therapeutic effect. The research results have been published in the international journal Small.

NIR-II phototheranostics have shown great prospects in tumour theranostics due to the depressed photon absorption and scattering by biological samples and can achieve deeper tissue penetration and higher maximum permissible exposure to lasers. However, most current NIR-II probes are in an ‘always on’ mode, which emit invariable fluorescence signals in both lesion and normal tissues owing to their non-specific effects. Such ‘always on’ signal mode can lead to a low tumour-to-normal tissue signal ratio, limited sensitivity and specificity, and even ‘false positive’ results. The non-specific diagnosis and treatments may cause irreversible damage to normal tissues during the off-target theranostic period.

Some activatable NIR-II phototheranostic probes have been fabricated to precisely distinguish lesions from normal tissues in response to TME. Despite excellent diagnostic specificity, current activatable NIR-II probes are mainly limited by complex chemical synthesis steps. In addition, to deliver the fluorophore, it may be necessary to introduce excess components, which might cause some excipient side effects. Therefore, it is highly desirable to develop a facile method to fabricate TME activatable NIR-II phototheranostic systems for improving the diagnosis specificity and therapeutic efficacy toward tumours.

In view of this, the research team developed a TME-activated phototheranostic nanoplatform (AFD NPs) based on the principle of Förster resonance energy transfer (FRET). The AFD NPs are fabricated through self-assembly of Ag2S QDs (NIR-II fluorescence probe) and ultra-small semiconductor polymer dots (DBZ Pdots, NIR-II fluorescence quencher) utilising Fe(III) as coordination nodes. In normal tissues, the AFD NPs maintain themselves in an ‘off’ mode, due to the FRET between Ag2S QDs and DBZ Pdots. However, the NIR-II fluorescence signal of AFD NPs can be rapidly ‘turned on’ by the overexpressed glutathione (GSH) in tumour tissues, resulting in significantly enhanced tumour-to-normal tissue (T/NT) signal ratio for tumour-specific diagnosis. Moreover, the released Pdots and reduced Fe(II) ions provide NIR-II photothermal therapy (PTT) and chemodynamic therapy (CDT), respectively. The GSH depletion and NIR-II PTT effect further aggravate CDT-mediated oxidative damage toward tumours, achieving the synergistic anti-tumour therapeutic effect. The work provides a promising strategy for the development of TME-activated NIR-II phototheranostic nanoprobes.

Prof Zhao and Prof Shen are the corresponding authors of the study, and UM postdoctoral fellow Dai Yeneng is the first author. The project was supported by the Science and Technology Development Fund of Macao SAR (File no: 0043/2021/A1), the National Key R&D Programme of China (File no: 2019YFA0904403), and UM (File no: MYRG2022-00143-FHS). The full version of the research paper can be viewed at https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202206053.

Source: Faculty of Health Sciences
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