Assembly of upconversion nanophotosensitizer in vivo to achieve scatheless real-time imaging and selective photodynamic therapy

Abstract

A perfect "off" to "on" switch of the therapeutic function is very important to minimize the phototoxicity of nanoplatforms assisted imaging-guided photodynamic therapy (PDT) of cancer. Current approaches rely on preloaded photosensitizers, where the off/on state of PDT is regulated by the sensitizing light of photosensitizers. However, the photoactivities inevitably occur when imaging/diagnosis or exposure to sunlight, etc. These preloading approaches will cause the damage to normal cells and the photosensitivity to the skin. Taking upconversion photodynamic therapy as an example we report here a biorthogonal chemistry solution to circumvent this problem. The luminescence upconversion nanoparticles (UCNPs) are anchored with one handle of click reaction and targeting entity, these nanoplatforms enable the imaging/labelling/tracking, especially for imaging-guided surgery. Once they are targeted, the photosensitizers armed with the other match handle will be injected in situ and click reaction will occur between the two handles to link the photosensitizers closely with the targeted nanoplatforms in a very short time, enabling the PDT function of the nanoplatforms. Proof of principle has been demonstrated in vitro and in vivo. This approach can be readily extended to chemotherapy, radiotherapy, etc. to overcome the side effect of these therapies of cancers.

Biomedical applications of copper-free click chemistry: in vitro, in vivo, and ex vivo

“…Tumor VEGF (vascular endothelial growth factor receptor 2) imaging by ultrasound 54 Antivascular endothelial growth factor receptor 2 antibody (TCO-antiVEGFR2)/Tz-modied microbubbles iEDDA Acute thrombus imaging by ultrasound 55 AntiCD62p-TCO/Tz-modied microbubbles iEDDA Tumor-targeted liposomes for drug delivery 25 Ac 4 ManNAz/DBCO-modied liposome SPACC Tumor-targeted photosensitizer delivery 27 Ac 4 ManNAz-loading chitosan nanoparticles/DBCO-modied chitosan nanoparticles SPACC Tumor-targeted doxorubicin delivery 56 Peptide-modied Ac 4 ManNAz/DBCO-modied doxorubicin SPACC Upconversion nanoparticle-based photodynamic therapy 57 Upconversion NP modied with Tz groups/norborane (NB)-conjugated rose bengal (RB) iEDDA Endothelial progenitor cell therapy for myocardiac infarction 58 Azide-modied CD34 antibody/DBCO-modied CD41 antibody SPACC Ex vivo Glycoproteomic analysis of intact and hypertrophy hearts 59 Ac 4 ManNAz/DBCO-Fluor 488 SPACC…”

“…In 2019, Feng et al introduced an assembly of upconversion nano-photosensitizers based on click chemistry in vivo. 57 This system is composed of upconversion NPs modied with Tz groups (UCNP-Tz) and a norborane (NB)-conjugated photosensitizer, rose bengal (RB). The UCNP-Tz was further modied with folate (FA) to target the receptors on tumor cells.…”

Lanthanide conjugates as versatile instruments for therapy and diagnostics

“…A lot of research deals with lanthanide-doped UCNPs as they are excitable in the deeper-tissue penetrating NIR region. [77][78][79] Recently, PDT-related apoptosis of certain cancer cell lines after excitation of UCNPs with a low-power 980 nm laser has been reported. 80 Nevertheless, quantum yields of the UCNPs as well as their targeting properties still have to be improved.…”

A NIR-I light-responsive superoxide radical generator with cancer cell membrane targeting ability for enhanced imaging-guided photodynamic therapy

“…The NIR-I bio-window (750-1000 nm) with higher tissue penetration, lower auto-uorescence, minimum photodamage to living organisms, and a lower and higher signal-tonoise ratio and detection sensitivity is in great demand for biological applications. [30][31][32][33] In this regard, NIR-I responsive uorescent PSs which can follow the type-I mechanism are advantageous for efficient PDT.…”