Advancing Cancer Treatment: Innovative Materials in PDT and Diagnostic Integration

Abstract

The diagnosis and treatment of cancers have become a significant challenge in overcoming malignant diseases. Early detection of tumors and timely targeted therapy can greatly impede the rapid deterioration of cancers. In recent years, nano-systems based on photodynamic materials have shown great progress in tumor diagnosis and treatment applications. With the continuous exploration of tumor-specific targets and the development of photodynamic nanoparticles, the generation of new nanoparticles that are target-specific, highly sensitive, and biosafe for integrated diagnosis and therapy is realistic. This review introduces the rational basis for photosensitizer-based materials for integrating cancer diagnosis and anti-cancer therapy, types and characteristics of organic and inorganic photosensitizers currently used for PDT treatment, photosensitive nano-materials with dual detection and therapeutic properties the advancement in developing photo-dynamic nano-systems showing potential in integrated diagnosis and therapeutic applications. We also introduce current strategies for optimizing nano-systems with the properties for enhancing targeting ROS release and accurate imaging, combining therapeutic efficacy, as well as biosafety of the integrative materials for PDT application, providing references for the coordinated optimization of photosensitizer design and clinical translation.

Keywords: advanced imaging technology; integrated diagnosis and treatment; novel nano-systems; photodynamic therapy; precision anti-cancer therapy; tumor targeting.

Graphical abstract

Figure 1

Schematic representation of the luminescence and photodynamic excitation mechanisms in photosensitizers.

Figure 2

Some representative organic photosensitizers, based on which derivatives with modified structures and special characterizations or functions can be developed.(A) Porphyrin. (B) Chlorin e6. (C) Cyanine dye (C11). (D) Phthalocyanines. (E) Methylene blue. (F) 4,4-difluoro-boradiazaindacene.

Figure 3

Single-excitation three-emission D/UCNPs for tumor microenvironment-responsive fluorescence imaging and chemo/photo-dynamic combination therapy. The NIR-II fluorescence imaging of _cgAuNCs was enhanced by endogenous glutathione response, while doxorubicin loaded on the nanoparticles was utilized for chemical therapy, and the photosensitizer methylene blue exerted its photodynamic therapy effects. Source: Reprinted from Hu S, Huang L, Zhou L et al. Single-excitation triple-emission down-/up-conversion nanoassemblies for tumor microenvironment-enhanced ratiometric NIR-II fluorescence imaging and chemo-/photodynamic combination therapy. Anal Chem. 2023;95(7):3830–3839. Copyright 2023, with permission from American Chemical Society.

Figure 4

Cell-selective biotin conjugated glutathione-responsive tris (phthalocyanine) for smart targeted photodynamic therapy, which achieves fluorescence activation and photodynamic treatment through the cleavage by glutathione near tumor cells and generates phthalocyanine monomers. Source: Reprinted from Chow SYS, Zhao S, Lo PC et al. A cell-selective glutathione-responsive tris(phthalocyanine) as a smart photosensitiser for targeted photodynamic therapy. Dalton Trans. 2017;46(34):11,223–11229. Copyright 2017, with permission conveyed through Copyright Clearance Center, Inc.

Figure 5

An in situ convertible nanoplatform with supramolecular cross-linking-triggered complementary functions—UCNP@MnOx-Hyp to enhance cancer photodynamic therapy. Source: Reprinted from Zhao M, Zhuang H, Li B et al. In situ transformable nanoplatforms with supramolecular cross-linking triggered complementary function for enhanced cancer photodynamic therapy. Adv Mater. 2023;35(20):e2209944. Copyright 2023, with permission from Wiley-Blackwell. © 2023 Wiley-VCH GmbH.

Figure 6

B-BDP-CL-CPT used for integrated cancer diagnosis and anti-cancer treatment. B-BDP-CL-CPT is activated in GSH-positive cancer cells, then emits fluorescence, realizing the generation of ROS and release of CPT, a chemotherapeutic drug. Source: Reprinted from Hu P, Xu G, Yang D-C et al. An advanced multifunctional prodrug combining photodynamic therapy with chemotherapy for highly efficient and precise tumor ablation. Dyes Pigm. 2022;205:110500. Copyright 2022, with permission from Elsevier.

Figure 7

Dual-emissive semiconducting polymer nanoparticles (SPNs) generate phosphorescent quenching signals and ROS through FRET effect after exposure to light in vivo. Source: Reprinted from Jiang J, Qian Y, Xu Z et al. Enhancing singlet oxygen generation in semiconducting polymer nanoparticles through fluorescence resonance energy transfer for tumor treatment. Chem Sci. 2019;10(19):5085–5094. Copyright 2019, with permission from Royal Society of Chemistry.

Figure 8

Major targets for anti-cancer therapy using nanoparticles. Some representative targets associated with solid cancerous tumors are depicted. CAFs, cancer-associated fibroblasts; ECs, endothelial cells; TAMs, tumor asso_x0002_ciated macrophages. Source: Reprinted from Sharma N, Bietar K, Stochaj U et al. Targeting nanoparticles to malignant tumors. BBA-REV CANCER. 2022;1877(3):188703. Copyright 2022, with permission from Elsevier.