This review presents a robust strategy to design photosensitizers (PSs) for various species. Photodynamic therapy (PDT) is a photochemical-based treatment approach that involves the use of light combined with a light-activated chemical, referred to as a PS. Attractively, PDT is one of the alternatives to conventional cancer treatment due to its noninvasive nature, high cure rates, and low side effects. PSs play an important factor in photoinduced reactive oxygen species (ROS) generation. Although the concept of photosensitizer-based photodynamic therapy has been widely adopted for clinical trials and bioimaging, until now, to our surprise, there has been no relevant review article on rational designs of organic PSs for PDT. Furthermore, most of published review articles in PDT focused on nanomaterials and nanotechnology based on traditional PSs. Therefore, this review aimed at reporting recent strategies to develop innovative organic photosensitizers for enhanced photodynamic therapy, with each example described in detail instead of providing only a general overview, as is typically done in previous reviews of PDT, to provide intuitive, vivid, and specific insights to the readers.

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy.

Among the many challenges in medicine, the treatment and cure of cancer remains an outstanding goal given the complexity and diversity of the disease. Nanotheranostics, the integration of therapy and diagnosis in nanoformulations, is the next generation of personalized medicine to meet the challenges in precise cancer diagnosis, rational management and effective therapy, aiming to significantly increase the survival rate and improve the life quality of cancer patients. Different from most conventional platforms with unsatisfactory theranostic capabilities, supramolecular cancer nanotheranostics have unparalleled advantages in early-stage diagnosis and personal therapy, showing promising potential in clinical translations and applications. In this review, we summarize the progress of supramolecular cancer nanotheranostics and provide guidance for designing new targeted supramolecular theranostic agents. Based on extensive state-of-the-art research, our review will provide the existing and new researchers a foundation from which to advance supramolecular cancer nanotheranostics and promote translationally clinical applications.

Supramolecular cancer nanotheranostics

Photo-driven theranostics, also known as phototheranostics, relying on the diverse excited-state energy conversions of theranostic agents upon photoexcitation represents a significant branch of theranostics, which ingeniously integrate diagnostic imaging and therapeutic interventions into a single formulation. The combined merits of photoexcitation and theranostics endow photo-driven theranostics with numerous superior features. The applications of aggregation-induced emission luminogens (AIEgens), a particular category of fluorophores, in the field of photo-driven theranostics have been intensively studied by virtue of their versatile advantageous merits of favorable biocompatibility, tuneable photophysical properties, unique aggregation-enhanced theranostic (AET) features, ideal AET-favored on-site activation ability and ready construction of one-for-all multimodal theranostics. This review summarised the significant achievements of photo-driven theranostics based on AIEgens, which were detailedly elaborated and classified by their diverse theranostic modalities into three groups: fluorescence imaging-guided photodynamic therapy, photoacoustic imaging-guided photothermal therapy, and multi-modality theranostics. Particularly, the tremendous advantages and individual design strategies of AIEgens in pursuit of high-performance photosensitizing output, high photothermal conversion and multimodal function capability by adjusting the excited-state energy dissipation pathways are emphasized in each section. In addition to highlighting AIEgens as promising templates for modulating energy dissipation in the application of photo-driven theranostics, current challenges and opportunities in this field are also discussed.

The fast-growing field of photo-driven theranostics based on aggregation-induced emission.

Pancreatic cancer, one of the most lethal malignancies, compromises the performance of traditional therapeutic regimens in the clinic because of stromal resistance to systemic drug delivery and poor prognosis caused by tumor metastasis. Therefore, a biocompatible therapeutic paradigm that can effectively inhibit pancreatic tumor growth while simultaneously eliminating tumor metastasis is urgently needed. Herein, supramolecular nanofibrils are fabricated through coassembly of clinically approved immunomodulatory thymopentin and near-infrared indocyanine green for localized photothermal immunotherapy of pancreatic tumors. The resulting long-range ordered fibrous nanodrugs show improved photophysical capabilities for fluorescence imaging and photothermal conversion and significantly promote the proliferation and differentiation of antitumor immune cells. Hence, the integration of rapid photothermal therapy and moderate immunomodulation for inhibiting tumor growth and eliminating tumor metastasis is promising. The utilization of clinically approved molecules to construct nanodrugs administered via localized injection amplifies the complementary photothermal immunotherapeutic effects of the components, creating opportunities for clinical translation as a treatment for pancreatic cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.202103733

Supramolecular Nanofibrils Formed by Coassembly of Clinically Approved Drugs for Tumor Photothermal Immunotherapy

Microbial infectious diseases, especially those caused by new and antibiotic-resistant pathogenic microbes, have become a significant threat to global human health. As an antibiotic-free therapy, phototherapy is a promising approach to treat microbial infections due to its spatiotemporal selectivity, non-invasiveness, minimal side effects, and broad antimicrobial spectrum. Although organic photosensitizer-based antimicrobial phototherapy has been extensively studied over the last decade, there has been no specific review article on this topic yet. It is important and timely to summarize recent research progress in this field. This tutorial review highlights the concept and significance of phototherapy and summarizes innovative types of organic photosensitizers with design strategies to deal with microbial infections. In addition, examples of organic antimicrobial photosensitizers, including antibacterial photosensitizers, antiviral photosensitizers, and antifungal photosensitizers are discussed. Finally, current challenges and future directions of organic photosensitizer-based phototherapy for clinical antimicrobial applications are presented. We believe that this tutorial review will provide general guidance for the future development of efficient photosensitizers and encourage preclinical and clinical studies for phototherapy-mediated antimicrobial treatments.

Organic photosensitizers for antimicrobial phototherapy.

Nano theranostics platforms that utilize proteins

Cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) are essential biothiols for cellular growth, metabolism, and maintenance of a biological system. Thus, the detection of biothiols is highly important for early diagnosis and evaluation of disease progression. In this article, a series of sulfonyl aza-BODIPYs was synthesized, characterized, and examined by 1H-NMR, 13C-NMR, crystallization, photophysical properties and DFT calculation. Among these structures, a fluorescent probe, BDP-1, exhibited selective detection of Cys among various biothiols via nucleophilic aromatic substitution and typical size of Cys molecules. BDP-1 showed color change and near-infrared (NIR) fluorescence enhancement after reaction with Cys to generate BDP-OH, confirmed by HRMS. The red shift of absorption wavelength showed a similar tendency resulting in time-dependent density functional theory (TD-DFT). Furthermore, the calculated detection limit of BDP-1 toward Cys was 5.23 μM. This probe facilitates the colorimetric and fluorescent detection of Cys over other biothiols.

/pdf/a-molecular-design-towards-sulfonyl-aza-bodipy-based-nir-3quf11p9zh.pdf

A molecular design towards sulfonyl aza-BODIPY based NIR fluorescent and colorimetric probe for selective cysteine detection

Polydiacetylenes Containing 2‐Picolylamide Chemosensor for Colorimetric Detection of Cadmium Ions

The ability to detect hypochlorite (HOCl/ClO-) in vivo is of great importance to identify and visualize infection. Here, we report the use of imidazoline-2-thione (R 1 SR 2 ) probes, which act to both sense ClO- and kill bacteria. The N2C=S moieties can recognize ClO- among various typical reactive oxygen species (ROS) and turn into imidazolium moieties (R 1 IR 2 ) via desulfurization. This was observed through UV-vis absorption and fluorescence emission spectroscopy, with a high fluorescence emission quantum yield (ՓF = 43-99%) and large Stokes shift (∆v∼115 nm). Furthermore, the DIM probe, which was prepared by treating the DSM probe with ClO-, also displayed antibacterial efficacy toward not only Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum s-lactamase-producing Escherichia coli (ESBL-EC), that is, antibiotic-resistant bacteria. These results suggest that the DSM probe has great potential to carry out the dual roles of a fluorogenic probe and killer of bacteria.

/pdf/hypochlorite-activated-fluorescence-emission-and-3x7c40fs74.pdf

Yeonghwan Choi

Papers

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy.

Nano theranostics platforms that utilize proteins

A molecular design towards sulfonyl aza-BODIPY based NIR fluorescent and colorimetric probe for selective cysteine detection

Polydiacetylenes Containing 2‐Picolylamide Chemosensor for Colorimetric Detection of Cadmium Ions

Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications.