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.

A selective colorimetric and fluorometric chemosensor based on conjugated polydiacetylenes for cadmium ion detection

In this article, we designed and synthesized the thionated NpImidazole derivatives BS and NS, new heavy-atom-free photosensitizers, which efficiently generate a triplet excited state with high singlet oxygen quantum yield. The introduction of the C═S bond to the NpImidazole core is essential for increasing spin-orbit coupling (SOC). The fluorescence emission of BS and NS was quenched at standard ambient temperature, accompanied with the increase in the ISC process from the singlet states to triplet excited states via thionation. BS and NS showed negligible dark cytotoxicity against HeLa cells in working concentration. In contrast, BS and NS rapidly induced cell death under blue light irradiation both under normoxia and hypoxia conditions. Our current study demonstrates that the C═S group can play an important role in type I ROS generation of PSs, which are unprecedented in the previous reports. Finally, the photophysical changes were assigned to the oxidative desulfurization of the C═S group of BS and NS to the C═O group of the corresponding BO and NO via hypochlorite. The combined results demonstrated the dual function of BS and NS as a fluorescent imaging agent for ClO- and an anti-cancer therapeutic by PDT that showed the potential strategy for "one-for-all" and multifunctional agents.

Molecular Design toward Heavy-Atom-free Photosensitizers Based on the C═S Bond and their Dual Functions in Hypoxia Photodynamic Cancer Therapy and ClO- Detection.

Nano theranostics platforms that utilize proteins

We prepared the monomer PCDA-HP composed of 5-hydroxy-N 1,N 3-bis(pyridin-2-ylmethyl)isophthalamide (HP) as a cadmium ion tweezer and then polymerized them to form a polydiacetylene (PDA)-based sensor (PDA-HP), which displayed selective and sensitive colorimetric and fluorometric change upon addition of a cadmium ion (Cd2+) at both pH 7.4 and 6.8. The PDA-HP polymer was highly selective for Cd2+ over other metal ions with colorimetric change. In addition, the PDA-HP chemosensor also showed a red fluorescence change in the presence of Cd2+ at both pH 7.4 and 6.8. Naked-eye detection of Cd2+ was accomplished in an aqueous solution through a PDA-based sensor system. Finally, the lowest energy structure of an HP chelator was obtained by the crystal structure and density functional theory (DFT) calculations.

Thanh Chung Pham

Papers

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy.

A selective colorimetric and fluorometric chemosensor based on conjugated polydiacetylenes for cadmium ion detection

Molecular Design toward Heavy-Atom-free Photosensitizers Based on the C═S Bond and their Dual Functions in Hypoxia Photodynamic Cancer Therapy and ClO- Detection.

Nano theranostics platforms that utilize proteins

Visual Simultaneous Detection and Real-Time Monitoring of Cadmium Ions Based on Conjugated Polydiacetylenes.