Two-Photon Excited FRET Dyads for Lysosome-Targeted Imaging and Photodynamic Therapy

Abstract

Two-photon excitable fluorescent dyes with integrated functions of targeted imaging and photodynamic therapy (PDT) are highly desired for the development of cancer theranostic agents. Herein, fluorescence resonance energy transfer (FRET) dyads, AceDAN-HPor-Lyso (1a) and AceDAN-ZnPor-Lyso (1b), were developed for two-photon excited (TPE) lysosome-targeted fluorescence imaging and PDT of cancer cells. Under one-photon or two-photon excitation, the AceDAN donor can effectively transfer the excited state energy to the porphyrin acceptor via high efficient FRET, leading to the generation of deep-red fluorescence and singlet oxygen for cell imaging and PDT, respectively. 1a and 1b exhibit high photocytotoxicity and low dark cytotoxicity, in addition to strong lysosomal targeting capability in living cells. By taking the advantages of the two-photon absorption properties of the AceDAN donor and the properly distributed S and T states of the porphyrin acceptor, the AceDAN-porphyrin dyads 1a and 1b have been successfully applied to TPE-fluorescence imaging for tracking the significant morphology changes of cancer cells under two-photon laser irradiation.

Resonance Energy Transfer: From Fundamental Theory to Recent Applications

“…Since the incident light in two-photon RET is lower in energy compared to RET, photo-destruction of living tissue can be circumvented. Therefore, biological applications of this process have arisen, including photodynamic therapy [153][154][155][156][157][158][159][160] and bioimaging [155,[160][161][162][163].…”

Photodynamic Therapy Directed by Three‐Photon Active Rigid Plane Organic Photosensitizer

“…It is worth noting that multi‐photon PDT reported in the literature is mainly achieved with nanomaterials [ 32–35 ] and complexes. [ 36–39 ] These are mostly for 2P PDT, while PDT based on 3P like U‐TsO are rarely reported. Besides, U‐TsO has low dark toxicity (Figure 2d) and is structurally innovative thus might provide new strategy for PDT agent design.…”

Quantum electrodynamics in modern optics and photonics: tutorial

“…Therefore, biological uses, such as photodynamic therapy and bioimaging, number prominently among the experimental applications that followed, soon after the initial QED-based prediction [175]; see, for example, Refs. [176][177][178][179][180][181][182][183][184][185][186][187]. A more exotic nonlinear effect discovered using QED is SHG mediated by six-wave mixing [188,189], which affords coherent second-harmonic production in isotropic media where Tutorial second-harmonic conversion is generally forbidden.…”