Abstract
The development of effective and safe tumor photothermal therapeutic strategies has attracted considerable 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 consisted of upconversion luminescent probes (NRhD) modified with polyethylene glycol (PEG) of various lengths. The continuous external irradiation-free photothermal NRhD-PEG-4 NPs with pKa 6.70 displayed 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 allowing 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 upconversion 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 nanoparticles. 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.
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