Rational design of pH-activated upconversion luminescent nanoprobes for bioimaging of tumor acidic microenvironment and the enhancement of photothermal therapy

The development of effective and safe tumor photothermal therapeutic strategies has attracted con-siderable attention. Herein, we synthesized tumor microenvironment (TME)-activatable self-assembling organic nanotheranostics (NRhD-PEG-X NPs (X = 1, 2, 3, and 4)) for precise tumor targeting and upconversion image-guided photothermal therapy (PTT). The amphiphilic polymer NRhD-PEG-X con-sisted of upconversion luminescent probes (NRhD) modified with polyethylene glycol (PEG) of vari-ous lengths. The continuous external irradiation-free photothermal NRhD-PEG-4 NPs with pKa 6.70 dis-played high sensitivity and selectivity to protons, resulting in the turn-on upconversion luminescence and enhanced photothermal properties in the acidic TME without asynchronous therapy and side effects. This nanotheranostic offers acidic activatability, tumor targetability, and PTT enhancement, thus allow-ing autofluorescence-free upconversion luminescent imaging-guided precision PTT. Our strategy affords a paradigm to develop activatable theranostic nanoplatforms for precision medicine.Statement of significanceAs a hyperthermia-based treatment, activatable photothermal therapy (PTT) is highly significant in tumor treatment. Herein, we develop acidic tumor microenvironment-activatable nanotheranostics for upconver-sion luminescent imaging-guided diagnosis and precision tumor-targeted PTT. PEGylation of upconversion dyes not only could self-assemble to yield organic nanoparticles in water, but it could also significantly improve biocompatibility, stability, and circulation time and tune significantly the pKa value of nanopar-ticles. In an acidic tumor microenvironment, NRhD-PEG-4 NPs with pKa 6.70 show high sensitivity to release NRhDH+-PEG-4 NPs, which exhibit good upconversion luminescence and enhanced photothermal effect. Therefore, upconversion luminescence imaging-guided precision PTT has high potential to enhance cancer diagnostic and therapeutic efficiency.(c) 2022 Published by Elsevier Ltd on behalf of Acta Materialia Inc.

Automated summary

In this study, tumor microenvironment-activatable self-assembling organic nanotheranostics were synthesized for precise tumor targeting and upconversion image-guided photothermal therapy. The nanotheranostics showed high sensitivity and selectivity in the acidic tumor microenvironment, allowing for enhanced upconversion luminescence and photothermal effect. This research provides a new approach for the development of activatable therapeutic nanoplatforms.