Emerging Strategies in Enhancing Singlet Oxygen Generation of Nano-Photosensitizers Toward Advanced Phototherapy

The great promise of photodynamic therapy(PDT) has thrusted the rapid progress of developing highly effective photosensitizers(PS) in killing cancerous cells and bacteria. To mitigate the intrinsic limitations of the classical molecular photosensitizers, researchers have been looking into designing new generation of nanomaterial-based photosensitizers(nano-photosensitizers) with better photostability and higher singlet oxygen generation(SOG) efficiency, and ways of enhancing the performance of existing photosensitizers. In this paper, we review the recent development of nano-photosensitizers and nanoplasmonic strategies to enhance the SOG efficiency for better PDT performance. Firstly, we explain the mechanism of reactive oxygen species generation by classical photosensitizers, followed by a brief discussion on the commercially available photosensitizers and their limitations in PDT. We then introduce three types of new generation nanophotosensitizers that can effectively produce singlet oxygen molecules under visible light illumination, i.e., aggregation-induced emission nanodots, metal nanoclusters (< 2 nm), and carbon dots. Different design approaches to synthesize these nano-photosensitizers were also discussed. To further enhance the SOG rate of nano-photosensitizers, plasmonic strategies on using different types of metal nanoparticles in both colloidal and planar metal-PS systems are reviewed. The key parameters that determine the metal-enhanced SOG(ME-SOG) efficiency and their underlined enhancement mechanism are discussed. Lastly, we highlight the future prospects of these nanoengineering strategies, and discuss how the future development in nanobiotechnology and theoretical simulation could accelerate the design of new photosensitizers and ME-SOG systems for highly effective image-guided photodynamic therapy.

Synthesis,Characterization,and Linear and Nonlinear Optical Properties of Phenylene-vinylene Based Chromophores for Singlet Oxygen Generation

A series of symmetrical and unsymmetrical phenylene-vinylene （PV） based chro- mophores with the molecular configuration of donor-π-donor （D-g-D） were prepared and characterized. Iodine was first introduced into the Jr-conjugation backbone of the PV based chromophores in order to study the heavy atom effect on their linear absorption, two-photon absorption （TPA） properties, as well as singlet oxygen generation properties. TPA cross-sections of these chromophores were investigated by using the two-photon excited fluorescence method. The unsymmetrical chromophores were found to have larger TPA cross-section values compared to their symmetrical counterparts. For one of the unsymmetrical chromophores with the iodine incorporation, a large TPA cross section value with quenched emission was found. The decreased fluorescence quantum yield of a molecule can be ascribed to the increased intersystem crossing, which is favorable for enhancing the singlet oxygen generation. Therefore, the unsymmetrical PV based chromophores with heavy atom incorporation are promising singlet oxygen sensitizers for the photodynamic therapy application.

Efficient singlet oxygen generation by excitonic energy transfer on ultrathin g-C_(3)N_(4) for selective photocatalytic oxidation of methyl-phenyl-sulfide with O_(2)

Efficient generation of singlet oxygen(1 O_(2)) by an excitonic ene rgy transfer process is highly desired on a semiconductor photocatalyst for selective oxidation of methyl phenyl sulfide(MPS).Herein,it is demonstrated that a large amount of 1 O_(2) is produced on pristine graphitic carbon nitride(CN) nanosheet compared with bismuth oxybromide(BiOBr) and comme rcial P25 titanium dioxide(TiO_(2)).This leads to a certain photoactivity of CN for MPS oxidation.The observed ~77% selectivity for CN depends on the competitive results of excitonic energy transfer for 1 O_(2) formation and charge carrier separation for superoxide radical(O_(2)·) production,which are based on the phosphorescence spectra and electron paramagnetic resonance signals,respectively.Moreover,ultrathin CN nanosheets are synthesized by thermal treatment with the cyanuric acid-melamine hydrogen bonded aggregates as precursors.It is confirmed that the amount of produced 1 O_(2) could be increased by decreasing the thickness of resultant CN nanosheets.The optimized ultrathin CN nanosheet(~4 nm) exhibits excellent photoactivity with high selectivity(~99%).It is suggested that the excitonic energy transfer for 1 O_(2) formation is close related to the intrinsic exciton binding energy and the two-dimensional quantum confinement effect.This work establishes a basic mechanistic understanding on the excitonic processes in CN,and develops a feasible route to design CN-based photocatalysts for efficient 1 O_(2) generation.

Orthogonal carbazole-perylene bisimide pentad:a photoconversion-tunable photosensitizer with diversified excitation and excited-state relaxation pathways

Integrating multiple photosensitive properties into an“all-in-one”photosensitizer(PS)shows great promise for the treatment of cancers owing to synergistic effect among them.However,the development of such PSs,especially those that need a single laser source,remains a challenge.Herein,we report an orchestration of electron donors and acceptors in a propeller-like pentad,PBI-4Cz,where four carbazole(Cz)units are covalently linked to the ortho-positions of the perylene bisimide(PBI)core.Strong intramolecular donor-acceptor interaction significantly quenches the luminescence and largely extends the absorption spectra to near-infrared region.Excited-state dynamics investigated via femto-and nano-second transient absorption spectroscopy revealed exclusive charge separation of the PBI-4Cz within initial 0.5 ps when photoexcited regardless of which intermediate is involved.Energy dissipation of the resulting charge-separated state(PBI^(•−)-4Cz^(•−))is subjected to the toggle between intersystem-crossing toward excited triplet states and charge recombination toward ground states.Relative importance of the two pathways can be tuned by micro-environmental polarity,which endows PBI-4Cz remarkable performances of singlet-oxygen generation(>90.0%)in toluene and photothermal conversion(∼28.6%)in DMSO.Harnessing intrinsic photostability and excited-state processes of heavy-atom-free PBI derivatives not only holds a promise for multifunctional phototheranostics,but also provides a prototype for designing high-performance PSs with tunable photoconversion pathways.