Six-in-one peptide functionalized upconversion@polydopamine nanoparticle-based ratiometric fluorescence sensing platform for real-time evaluating anticancer efficacy through monitoring caspase-3 activity

Abstract

• Six-in-one ratiometric fluorescence sensing platform. • Highly sensitive and selective detection of caspase-3. • The anticancer efficacy evaluation of photothermal (PTT)-chemotherapy. • Real-time noninvasive evaluation of tumor response to PTT and chemotherapy of staurosporine (STS). Herein, a six-in-one peptide functionalized upconversion@polydopamine nanoparticle-based ratiometric fluorescence sensing platform (termed as UCNP@PDA@Cy3-pep) has been fabricated for monitoring the anticancer efficacy of photothermal-chemotherapy in real time through detection of caspase-3 activity. In this work, the upconversion nanoparticle (UCNP) core of UCNP@PDA was employed as an internal reference, while the PDA shell of UCNP@PDA was used as an acceptor of fluorescence resonance energy transfer (FRET) system, photothermal therapy (PTT) agent, loading agent of chemical drug and immobilization platform of Cy3 (donor of FRET) labeled peptide (Cy3-pep), which contains a specific caspase-3 substrate (DEVD) and active tumor-targeting motif (PSP). In the presence of caspase-3, the FRET system was broken through the enzymatic cleavage of DEVD, resulting in a recovery of Cy3 fluorescence emission. Under the optimal conditions, the ratio of recovered Cy3 fluorescence intensity with upconversion luminescent (UCL) intensity was linearly dependent on the caspase-3 concentration within the range of 0.5–50 ng mL −1 and the limit of detection (LOD) was calculated as 0.065 ng mL −1 . Using mouse-bearing MG-63 tumor as a model system, the capability of as-proposed UCNP@PDA@Cy3-pep has been successfully demonstrated through a real-time noninvasive evaluation of tumor response to PTT and chemotherapy of staurosporine (STS).