Photodynamic Therapy Of Cancer Research Articles

Hypericin-Mediated Photodynamic Therapy for Head and Neck Cancers: A Systematic Review

Background: Conventional treatments for cancers of the head and neck region are often associated with high recurrence rates and impaired quality of life. Photodynamic therapy (PDT) has emerged as a promising alternative, leveraging photosensitizers such as hypericin to selectively target tumour cells with minimal damage to surrounding healthy tissues. Objectives: We aimed to evaluate the efficacy and underlying mechanisms of hypericin-mediated PDT (HY-PDT) in treating head and neck cancers. Methods: Adhering to PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Embase, Scopus, and the Cochrane Library for studies published between January 2000 and December 2024. Inclusion criteria encompassed preclinical in vitro and in vivo studies and clinical trials focusing on HY-PDT for head and neck malignancies and its subtypes. Results: A total of 13 studies met the inclusion criteria, comprising both in vitro and in vivo investigations. HY-PDT consistently demonstrated significant cytotoxicity against squamous cell carcinoma cells through apoptotic and necrotic pathways, primarily mediated by ROS generation. Hypericin exhibited selective uptake in cancer cells over normal keratinocytes. Additionally, HY-PDT modulated the tumour microenvironment by altering cytokine profiles, such as by increasing IL-20 and sIL-6R levels, which may enhance antitumor immunity and reduce metastasis. Conclusions: HY-PDT emerges as a highly promising and minimally toxic treatment modality for head and neck cancers, demonstrating efficacy in inducing selective tumour cell death and modulating the immune microenvironment. Despite the encouraging preclinical evidence, significant methodological variability and limited clinical data necessitate further large-scale, standardized and randomized controlled trials.

Highly Photoreactive Semiconducting Polymers with Cascade Intramolecular Singlet Oxygen and Energy Transfer for Cancer-Specific Afterglow Theranostics.

Afterglow luminescence provides ultrasensitive optical detection by minimizing tissue autofluorescence and increasing the signal-to-noise ratio. However, due to the lack of suitable unimolecular afterglow scaffolds, current afterglow agents are nanocomposites containing multiple components with limited afterglow performance and have rarely been applied for cancer theranostics. Herein, we report the synthesis of a series of oxathiine-containing donor-acceptor block semiconducting polymers (PDCDs) and the observation of their high photoreactivity and strong near-infrared (NIR) afterglow luminescence. We reveal that PDCDs absorb NIR light to undergo a photodynamic process to generate singlet oxygen (1O2), which intramolecularly transfers to and efficiently reacts with the oxathiine block to form the afterglow oxathiine intermediates due to the low Gibbs free energy changes required for this photoreaction. Following intramolecular afterglow energy transfer from the oxathiine donor block to the acceptor block, NIR afterglow emission is produced from PDCDs. Owing to the efficient cascade intramolecular photochemical process, PDCD-based nanoparticles achieve a higher brightness and longer NIR emission compared to most reported afterglow agents, even after ultrashort photoirradiation for only 3 s. Furthermore, the cascade photochemical process within PDCD can be inhibited after bioconjugation with a quencher-linked peptide. This allows the construction of a cancer-activatable afterglow theranostic probe (CATP) that only switches on the afterglow signal and photodynamic function in the presence of a cancer-overexpressed enzyme. Thereby, CATP represents the first afterglow phototheranostic probe that permits cancer-specific detection and photodynamic cancer therapy under preclinical settings. In summary, this study provides a molecular guideline to develop afterglow probes from photoreactive polymers.

Discovering Cell-Targeting Ligands and Cell-Surface Receptors by Selection of DNA-Encoded Chemical Libraries against Cancer Cells without Predefined Targets.

Small molecules that can bind to specific cells have broad applications in cancer diagnosis and treatment. Screening large chemical libraries against live cells is an effective strategy for discovering cell-targeting ligands. The DNA-encoded chemical library (DEL or DECL) technology has emerged as a robust tool in drug discovery and has been successfully utilized in identifying ligands for biological targets. However, nearly all DEL selections have predefined targets, while target-agnostic DEL selections interrogating the entire cell surface remain underexplored. Herein, we systematically optimized a cell-based DEL selection method against cancer cells without predefined targets. A 104.96-million-member DEL was selected against MDA-MB-231 and MCF-7 breast cancer cells, representing high and low metastatic properties, respectively, which led to the identification of cell-specific small molecules. We further demonstrated cell-targeting applications of these ligands in cancer photodynamic therapy and targeted drug delivery. Finally, leveraging the DNA tag of DEL compounds, we identified α-enolase (ENO1) as the cell surface receptor of one of the ligands targeting the more aggressive MDA-MB-231 cells. Overall, this work offers an efficient approach for discovering cell-targeting small molecule ligands by using DELs and demonstrates that DELs can be a useful tool to identify specific surface receptors on cancer cells.

The Midas Touch by Iridium: A Second Near-Infrared Aggregation-Induced Emission-Active Metallo-Agent for Exceptional Phototheranostics of Breast Cancer.

Developing small organic molecular phototheranostic agents with second near-infrared (NIR-II) aggregation-induced emission (AIE) is paramount for the phototriggered diagnostic imaging and synchronous in situ therapy of cancer via an excellent balance of the excited states energy dissipations. In this study, a multifunctional iridium(III) complex is exploited by the coordination of an AIE-active N^N ancillary ligand with a trivalent iridium ion. The resultant complex DPTPzIr significantly outperforms its parent ligand in terms of absorption/emission wavelengths, reactive oxygen species (ROS) production, and photothermal conversion, which simultaneously endow DPTPzIr nanoparticles with matched absorption peak to commercial 808 nm laser, the longest NIR-II emission peak (above 1100 nm) among those previously reported AIE iridium(III) complexes, potentiated type-I ROS generation, and as high as 60.5% of photothermal conversion efficiency. Consequently, DPTPzIr nanoparticles perform well in multimodal image-guided photodynamic therapy-photothermal therapy for breast cancer in tumor-bearing mice, enabling precise tumor diagnosis and complete ablation with high biocompatibility. Our present work provides a simple, feasible, and effective paradigm for the development of advanced phototheranostic agents.

Changes in Levels of MiR-21, MiR-27a, MiR-221, and MiR-429 in the Thymus after Photodynamic Therapy and Surgical Treatment of Breast Cancer in Female Wistar Rats.

We studied the expression levels of microRNAs (miR-21, miR-27a, miR-221, and miR-429) in the thymus of female Wistar rats after surgical treatment of breast cancer (BC) and after photodynamic therapy for BC followed by tumor resection. In the group without treatment, the levels of pro-oncogenic miR-21, miR-27a, and miR-221 in the thymus were reduced in comparison with those in the group of intact control. After surgical treatment of BC, the levels of miR-21 and miR-27a in the thymus increased in comparison with those in BC without treatment. Surgical removal of the tumor followed by photodynamic therapy led to an even greater increase in the levels of miR-21 and miR-27a in the thymus in comparison with those in the group of surgical treatment alone. Expression of the tumor-suppressive miR-429 in the thymus significantly exceeds the levels in the BC without treatment and BC+surgery groups.

Impact of different 2D materials on the efficacy of photothermal and photodynamic therapy in 3D-bioprinted breast cancer.

The convergence of nanotechnology and tissue engineering has paved the way for innovative cancer treatments that leverage the unique light absorption properties of nanomaterials. Indeed, photothermal therapy (PTT) and photodynamic therapy (PDT) utilize nanomaterials to convert near-infrared light into therapeutic energy for cancer treatment. This study focuses on the application of poly(lactic-co-glycolic acid) (PLGA) scaffolds, enhanced by graphene oxide, Ti3C2Tx MXene, and TiS2 transition metal dichalcogenides for PDT and PTT treatments evaluated within 3D-bioprinted breast cancers. Our scaffolds were designed to exploit the photothermal conversion efficiency and capability to generate reactive oxygen species (ROS) to compare the specific features of each 2D material. We demonstrated a reduction in tumor viability under scaffold irradiation, along with the exploration of biological responses to damage such as autophagy and pyroptosis, verifying that these scaffolds can differentially induce these processes depending on the light responsiveness of each material. The integration of these materials within 3D-printed scaffolds does not only enhance the therapeutic efficacy of PTT and PDT, but also offers a precise method to control the cellular environment after therapy, i.e. tissue regeneration and antibacterial effects, providing insights into the potential for these technologies to be adapted for personalized medicine for breast cancer treatment and reconstruction.

Multifunctional Ru(III)/Fe3O4/DNA nanoplatform for photothermal-enhanced photodynamic and chemodynamic cancer therapy

Among the many cancer treatment methods, there have been many reports on the use of nanoplatforms with single treatment methods such as photothermal, photodynamic or chemodynamic for cancer treatment. In this study, Ru(III) with photodynamic effect and Fe3O4 nanoparticles with photothermal and chemodynamic effects are connected through long DNA chains with efficient active targeting rolling circle amplification to construct Ru(III)/Fe3O4/DNA nano-platform realizes the combination of photothermal, photodynamic and chemodynamic treatment, which significantly improves the therapeutic effect of the nano-platform. Its multiple active targeting capabilities reduce the damage to normal cells. Ru(III) has excellent photodynamic effect and can catalyze the respiration product NADH (Nicotinamide adenine dinucleotide)to produce highly oxidizing H2O2. Fe3O4 NPs has weak absorption at 808 nm indicates that it can perform mild photothermal treatment, and the Fe2+ in it can react with H2O2 to produce ·OH and participate in chemodynamic treatment. Each repeating unit on the rolling circle amplified DNA long chain is connected to the AS1411 aptamer that can actively target cancer cells. Unlike the passive targeting of other nanomedicines, active and efficient targeting is achieved, and a small amount of drugs can achieve high efficacy. The therapeutic effect also reduces the damage to normal cells. The comprehensive killing effect of Ru(III)/Fe3O4/DNA can reach 85.1 %. Its high targeting of cancer cells can also be used for imaging detection of cancer cells. This new nanoplatform provides an idea for the synergy of multiple cancer treatments.

A preclinical design approach for translation of biohybrid photosensitive nanoplatform for photodynamic therapy of breast cancer.

Translating photodynamic therapy research into practice with high efficacy should follow characterization and optimization steps in an integrated process. In this way, integration of molecular-based simulations with in vitro and in vivo studies to produce more accurate models with higher prediction precision is inevitable. This study reports on the development a two-phase approach to design and synthesize, and characterize novel hybrid nano-photosensitizers to target breast cancer using molecular docking, microfluidic-based testing and animal studies. In the first phase, using pkCSM artificial intelligence tool and molecular docking, pharmacokinetic weaknesses of photoprotoporphyrin and its retention potential within albumin protein were identified. Biohybrid photosensitive nanoplatform were then synthesized using opto-microfluidics and characterized. In addition, an in-vivo method was used to qualitatively evaluate the opto-biological stability of the final optimized biohybrid nanoplatform. At the second phase, variables of photodynamic treatment were firstly optimized using design of experiment method for the optimized biohybrid photosensitive nanoplatform. Then, on-chip photodynamic studies were carried out in static and dynamic conditions. Results revealed that optimized biohybrid photosensitive nanoplatform as a nano-photosensitizer induced significant death of triple negative human cancer cells in static and dynamic cell cultures under optimized irradiation conditions. Consequently, the presented multiphase study that combined in-silico simulations with microfluidic-based synthesis and characterizations of nano-photosensitizers provided a more convergent model for development of efficacious cancer treatment for photodynamic therapy applications.

Gels in Heterogeneous Photocatalysis: Past, Present, and Future.

Photocatalysis has attracted more and more attention as a possible solution to environmental, water, and energy crises. Although some photocatalytic materials have already proven to perform well, there are still some problems that should be solved for the broad commercialization of photocatalysis-based technologies. Among them, cheap and easy recycling, as well as stability issues, should be addressed. Accordingly, the application of gels, either as a photocatalytic material or as its support, might be a good solution. In this review, various propositions of gel-based photocatalysts have been presented and discussed. Moreover, an easy nanoarchitecture design of gel-based structures enables fundamental studies, e.g., on mechanism clarifications. It might be concluded that gels with their unique properties, i.e., low density, high specific surface area, great porosity, and low-cost preparation, are highly prospective for solar-energy-based reactions, water treatment, photodynamic cancer therapies, and fundamental research.

Synthesis of multifunctional zinc(II) phthalocyanine and evaluation of in vitro cytotoxic activity for potential photodynamic therapy and targeting efficiency in prostate cancer

In this study, we aimed to synthesize a novel biotin-functionalized star-shaped poly(2-ethyl-2-oxazoline) (PEtOx) polymer with a zinc (II) phthalocyanine core (ZnPc-[PEtOx]4-Biotin) to enhance therapeutic efficacy through active targetability. ZnPc-[PEtOx]4 was prepared via cationic ring-opening polymerization, followed by conjugation to biotin and BODIPY using "click chemistry." The resulting Zn (II) phthalocyanine-functionalized polymer was characterized using GPC, FTIR, UV-vis, NMR, and fluorescence spectroscopy. ZnPc-[PEtOx]4-Biotin demonstrated an active targeting effect on prostate cancer cells (22Rv1, LNCaP, and PC-3), with higher affinity compared to in vitro cytotoxicity analysis against normal prostate epithelial cells, PNT1A, and prostate cancer cells (22Rv1, LNCaP, and PC-3) revealed low cytotoxicity, dependent on concentration. These findings suggest that the developed Zn(II) phthalocyanine-functionalized polymeric photosensitizer holds promise as an effective strategy for prostate cancer therapy, leveraging specific target recognition mechanisms.

Metal Doping Enabling Defective CoMo-Layered Double Hydroxide Nanosheets as Highly Efficient Photosensitizers for NIR-II Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) is attracting widespread attention as a promising strategy for tumor treatment. However, the efficacy of PDT is severely limited by the insufficient tissue penetration depth of the light source and low reactive oxygen species (ROS) generation efficiency. Herein, the metal doping strategy is reported to construct a series of defect-rich M-doped amorphous CoMo-layered double hydroxide (a-M-CoMo-LDH, M = Mn, Cu, Al, Ni, Mg, Zn) photosensitizers (PSs) for NIR-II PDT. Especially, M-doped CoMo-LDH nanosheets are synthesized through a simple hydrothermal method and then etched by acid treatment to prepare defect-rich a-M-CoMo-LDH nanosheets. Under NIR-II 1270 nm laser irradiation, the defect-rich a-Zn-CoMo-LDH nanosheets exhibit the optimal PDT performance compared with other a-M-CoMo-LDH nanosheets, and also possess much higher ROS production activity (3.9 times) than that of the pristine a-CoMo-LDH, with a singlet oxygen quantum yield up to 1.86, which is the highest among all the reported PSs. After polyethylene glycol (PEG) modification, the a-Zn-CoMo-LDH-PEG nanosheets can function as an effective inorganic PS for PDT, effectively inducing cell apoptosis in vitro and eradicating tumors in vivo. Notably, transcriptome sequencing analysis and further molecular validation highlight the critical role of the apoptotic/p53/AMPK/oxidative phosphorylation signaling pathways in a-Zn-CoMo-LDH-PEG-induced cancer cell apoptosis.

Tetramethyl Cucurbit[6]uril-Porphyrin Supramolecular Polymer Enhances Photosensitization.

Porphyrins serve as photosensitizers (PS) in the realm of cancer photodynamic therapy (PDT). Upon excitation by laser light, porphyrins are capable of converting molecular oxygen into highly cytotoxic singlet oxygen (1O2). However, the rigid π-conjugated structure of porphyrins frequently results in the formation of aggregates in aqueous solutions, which leads to the self-quenching of the excited state. Cucurbit[n]urils exhibit the capacity to stably bind with porphyrins via host-guest interactions, effectively inhibiting their aggregation and potentially enhancing the therapeutic efficacy of PDT. In this study, water-soluble tetramethyl cucurbit[6]uril (TMeQ[6]) was selected as the host, while four propionic acid group-appended porphyrin cationic (TPPOR) was utilized as guests to construct a supramolecular photosensitizer (TPPOR-2TMeQ[6]) in a molar ratio of 2:1. Further experimental findings demonstrate that the presence of TMeQ[6] inhibits the aggregation of TPPOR through non-covalent interactions. This inhibition reduces the energy difference between the excited singlet and triplet states, thereby enhancing the conversion efficiency of 1O2. Moreover, TPPOR-2TMeQ[6] exhibits favorable biocompatibility and minimal dark toxicity against breast cancer cells (4T1). Upon intracellular excitation, the levels of reactive oxygen species (ROS) significantly increase, inducing oxidative stress in 4T1 cells and leading to apoptosis. Consequently, the findings of this study suggest that the enhanced photosensitization achieved through this supramolecular approach is likely to promote the anticancer therapeutic effects of PDT, thereby broadening the application prospects of porphyrins within PDT systems.

Peroxisome-inspired T4 phage hybrid enzyme nanoreactors for photodynamic therapy of breast cancer

Peroxisome-inspired T4 phage hybrid enzyme nanoreactors for photodynamic therapy of breast cancer

Exploring the potential of 7,4′-di(diethylamino)flavylium as a novel photosensitizer for topical photodynamic therapy of skin cancer

Photodynamic therapy (PDT) is a minimally invasive therapeutic approach that has shown promising results in recent years, particularly in the dermatological clinical treatment of several pathologies, including neoplastic skin diseases. In light of the recent discovery of the photosensitizing properties of a water-soluble group of amino-based flavylium dyes, research efforts have led to the development of a novel synthetic dye with two diethylamino moieties in its structure, 7,4’-di(diethylamino)flavylium (7,4′diN(Et)2). This dye was tested as a potential photosensitizer for PDT of skin cancer. A single light dose of 22.5 J/cm2 efficiently killed SCC-25 (squamous cell carcinoma) and A375 (melanoma) cells, reducing cellular viability by more than 80% in the presence of the flavylium at 0.75 µM. Meanwhile, the negligible cellular toxicity of the dye in the absence of light stimulus points out a wide and safe therapeutic window. Interestingly, significant light-induced toxicity effects were still observed after washing out the compound before cell irradiation. Moreover, out of the three prototype flavylium-loaded hydrogels, each one based on a different polymer (Carbomer, Caesalpinia Spinosa Gum and Hydroxypropyl methyl cellulose), carbomer-based formulation stood out for its substantial absorbance and fluorescence increment and enhanced1O2 photogeneration activity compared to the flavylium in aqueous solution. The findings of this study provide valuable insights concerning the potential of this flavylium dye as a candidate for photodynamic therapy of skin cancer and strongly support the need for further testing in more advanced biological settings to fully assess its efficacy and safety.

Dual-modal overcoming of physical barriers for improved photodynamic cancer therapy via soft organosilica nanocapsules

Amidst the burgeoning field of cancer nanomedicine, dense extracellular matrices and anomalous vascular structures in the tumor microenvironment (TME) present substantial physical barriers to effective therapeutic delivery. These physical barriers hinder the optimal bioavailability of nanomedicine. Here, we propose a pioneering dual-modal strategy for overcoming physical barriers via soft organosilica nanocapsules (SMONs). Hyaluronidase-modified flexible spheres work by degrading the extracellular matrix and utilizing their flexible characteristics to enhance penetration into deeper layers. Compared with their stiff counterparts, the SMONs show diminished Young’s modulus, then the inherent softness of the SMONs confers distinct advantages, and significantly augmented cellular internalization within 4T1 cells, leading to an amplified in vitro photodynamic therapeutic effect. Furthermore, hyaluronidase-functionalized SMONs (SMONs-HAase) exhibit enhanced tumor penetration in 3D spheroids. Post incorporation of the photosensitizer chlorin e6, when administered intravenously, these soft organosilica nanocapsules amplify the efficacy of photodynamic therapy. In addition, RNA-seq analysis of SMONs-HAase-Ce6 shows it alters gene expression, degrading the extracellular matrix and impairing mitochondrial function. To sum up, this work elucidates the potential of a dual-modal strategy, highlighting the promise of SMONs in overcoming TME physical barriers and optimizing therapeutic outcomes.Graphical abstract

Slight modification of a G-quadruplex-targeted quinoxaline may boost type-1 photodynamic therapy for triple-negative breast cancer

G-quadruplexes (G4s) are potential drug targets in cancer treatment. However, the G4-targeted ligands seem to be lack of enough selectivity between tumors and normal tissues, appealing for more precise therapeutic strategies. Type-1 photodynamic therapy (PDT) is a promising strategy possessing excellent spatiotemporal precision for solid tumors with hypoxic microenvironment. However, rational design of type-1 photosensitizers that target G4s are never reported. In this study, we designed a novel G4-targeted ligand (DQ4) by introducing an electron-donating piperazine unit into our previously reported quinoxaline scaffold. Such a slight modification significantly eliminated its intrinsic emission, which made DQ4 a promising “turn-on” fluorescent probe for detecting G4s. Moreover, this modification greatly boosted the production of type-1 ROS, enabling DQ4 to be an excellent photosensitizer potentially for treating hypoxic solid tumors.

Photodynamic therapy for early and recurrent oral cancers and pre-malignant lesions. Need of the hour for India

Oral cancer rates in India surpass those in any other nation, with patients manifesting varied disease stages, including pre-malignant phases. Tobacco chewing promotes field cancerization, and related surgical interventions can be remarkably morbid. Advanced-stage patients with frequent recurrences undergo treatments that significantly degrade their quality of life. In such instances, Photodynamic Therapy (PDT) emerges as an invaluable tool, enhancing both the longevity and quality of life. This paper elucidates two such cases benefiting from PDT, spotlighting its potential in transforming cancer care in India.

Research progress of photodynamic therapy in the anti-tumor field

Abstract. Photodynamic therapy (PDT), which is based on activating photosensitizers by light of a certain wavelength to produce anti-tumor effects, has attracted much attention because of its non-invasiveness and high selectivity for tumors. In many tumor diseases with high mortality rates, PDT has achieved better therapeutic effects when combined with a variety of therapies and has become one of the most important methods for treating a variety of cancers. In this review, we have collected research on the application of PDT in cancer and its combination with chemotherapy, immunotherapy, and nanomaterials in recent years, aiming to show that the combination of PDT with other therapies deserves further exploration

Research progress of photodynamic therapy in antitumor therapies

Abstract. As one of the leading causes of disease death globally, conventional treatments for cancers have been developed, including surgery, chemotherapy, radiotherapy etc. However, some drawbacks restrain their therapeutic effects. Consequently, researchers have been struggling to develop novel strategies to cure tumors. Photodynamic therapy (PDT) is a significant means that utilizes light as well as photosensitizers to kill tumor cells. In PDT, a photosensitizer absorbs a photon and transfer to states with higher energy, then energy is released and generates free radicals and ground-state molecular oxygen by two distinct types of reaction to exert therapeutic functions. This review concentrates on the antitumor principles and mechanisms of PDT, common photosensitizers, combination of PDT and other cancer therapies and its effects on several typical cancers.

Cu-Bi2S3 nanorods promote reactive oxygen species production for photodynamic therapy of prostate cancer

Photodynamic therapy (PDT) has emerged as a promising cancer treatment approach due to its non-invasive and specifically targeted nature. However, the effectiveness of PDT is hindered by the complex synthesis of conventional photosensitizers and inadequate reactive oxygen species (ROS) generation. Here, we synthesize a copper-doped Bi2S3 (Cu-Bi2S3) nanorod to investigate its PDT potential against PCa. Compared with bulk Bi2S3 (58%), Cu-Bi2S3 nanorod caused 87% of PC3 cells to die under light. The dispersed Cu in the Bi2S3 bulk phase effectively inhibits the recombination of photogenerated electron-hole pairs, ultimately providing a high concentration of charge carriers. DFT calculations show that Cu doping causes the d-band center of Cu-Bi2S3, promoting the adsorption and activation of O2 on Cu-Bi2S3 to enhance ROS generation. This work offers a viable solution to the pressing scientific challenge of ROS generation, a key aspect of enhancing the efficacy of PDT for cancer treatment.