Compared with the monotherapy of PDT or CDT, BT-TPE@Fe-Lac can significantly increase the intracellular ROS levels to induce more tumor cell death under low drug doses and hypoxia-dependent conditions. This strategy leverages the unique properties of the TME to optimize therapeutic outcomes, offering a promising approach for the TME-responsive nanoplatform in advanced cancer therapy.

Exceptional multimodal imaging navigation has also been developed. Excellent theranostics performance was substantiated in diverse tumor models, implying that this synergistic strategy of phototheranostics and immunotherapy provides a paradigm shift in emerging CRISPR-mediated nanomedicines.

By freebayes analysis in treated samples, a stop-lost mutation was detected in pseudogene (RSL_RS06070), while the possible effect on down-stream genes including tsaD, acyl-CoA-desaturase, 30S ribosomal protein S6 and DUF424 family protein. The frameshift mutation was localized within clpB pseudogene belonging to stress-response heat-shock proteins.

Furthermore, silencing YAP or treating with its inhibitor, Verteporfin, attenuated PD-L1 expression induced by Gq/G11 mutations, thereby enhancing T cell activation and T cell-mediated cytotoxicity. Collectively, this study reveals a potential role of Gq/G11 mutations on immune evasion of UM, a new mechanism of Gq/11 mutations-induced tumorigenesis, highlighting Gq/G11 and YAP as potential immunotherapeutic targets and suggesting Verteporfin as an adjuvant for immunotherapy of UM patients with GNAQ or GNA11 mutations.

P1, N=5, Terminated, Roswell Park Cancer Institute | Active, not recruiting --> Terminated; Low accrual

P1, N=5, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=12 --> 5

P3, N=165, Recruiting, Biofrontera Bioscience GmbH | Trial completion date: Mar 2026 --> Jun 2026

P1, N=36, Recruiting, Impact Biotech Ltd | Suspended --> Recruiting

On the other hand, BRD-PS suppresses the expression of PD-L1 to avoid immune evasion. This work demonstrated the feasibility of utilizing a single photosensitizer to simultaneously induce immunogenic cell death and PD-L1 downregulation for synergistic cancer photoimmunotherapy.

In vivo PDT experiments showcased that TSPy-SS-P had excellent tumor retention capability, effective tumor ablation ability and good biocompatibility. This work provided a two-pronged strategy to design organelles targeted photosensitizers for H2S detection and effective PDT of tumors.

PNS might be effective for ICH treatment by enhancing lymphangiogenesis and the meningeal lymphatic drainage function, thereby attenuating inflammation and promoting neurological recovery. The role of PNS in regulation of MLVs was investigated for the first time. This study provides a novel insight for PNS in the medical therapy of ICH.

P2, N=30, Not yet recruiting, Therakos, LLC, a Mallinckrodt Company

The ABCG2 inhibitor (fumitremorgin C) and P-gp inhibitor (valspodar) effectively blocked the transport mediated by ABCG2 and P-gp of rose bengal and BPD... In summary, our study provided new knowledge that temoporfin, talaporfin sodium, methylene blue, and indocyanine green are not substrates of ABCG2, P-gp, or MRP1...Rose bengal is a substrate of ABCG2, P-gp, and MRP1. The results presented here indicate ABC transporter substrate status as a possible cause for cellular resistance to photodynamic therapy with rose bengal, redaporfin, and BPD.

A single systemic intravenous administration of PNBS/diABZI eradicated orthotopic mammary tumors in murine models, achieving long-term antitumor immune memory to inhibit tumor recurrence and metastasis and significantly improving long-term tumor-free survival. This work provides a design rule for boosting reactive oxygen species production by promoting the intersystem crossing process, highlighting the potential of Type I photosensitizer-polymer vehicles for augmenting STING immunotherapy.

P2, N=36, Not yet recruiting, Kiora Pharmaceuticals, Inc.

The results revealed that the kanamycin, velpatasvir, verteporfin, and temoporfin significantly decreased the binding of LIR to the p62 protein. Finally, we experimentally confirmed that Kanamycin can inhibit autophagy-associated acidic vesicular formation in breast cancer MCF-7 and MDA-MB 231 cells. These repositioned drugs may represent novel autophagy modulators in clinical management, warranting further investigation.

P1, N=36, Suspended, Impact Biotech Ltd | Trial completion date: Dec 2027 --> Dec 2028 | Not yet recruiting --> Suspended | Trial primary completion date: May 2026 --> May 2027

Our results indicated that dinaciclib and alvocidib exhibited similar activity and sensitivity in the neuroendocrine cluster. Also, a lineage factor named KLF5 recognized by inferred transcriptional factors activity could be suppressed by verteporfin.

P1/2, N=53, Recruiting, Roswell Park Cancer Institute | Not yet recruiting --> Recruiting | N=39 --> 53

Compared to PDT alone, combination therapy shows greater advantages in tumor immunotherapy. The combination therapy strategy provides new ideas for cancer immunotherapy.

It was found that porphyrin-PDI, Fe2-porphyrin-PDI, Zn-porphyrin-PDI, Mg-porphyrin-PDI, Zn-porphyrin combined with PDI through single bond (compound 1), and two acetylenic bonds (compound 2) in this work would be proposed as potential PS candidates for PDT process. This study was expected to provide PS candidates for the development of novel medicines in PDT.

P4, N=327, Not yet recruiting, University of Roma La Sapienza | Trial primary completion date: Jul 2027 --> Dec 2027

P2, N=15, Suspended, SonALAsense, Inc. | Trial completion date: Jul 2024 --> Oct 2024 | Terminated --> Suspended

P1, N=5, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=16 --> 5 | Trial completion date: Mar 2025 --> Jan 2026 | Trial primary completion date: Mar 2025 --> Feb 2024

The generation of ROS mediated by IrC, along with the direct inhibition of GPX4 and glutathione, synergistically increased cellular oxidative stress and the level of lipid peroxidation. This study provides an effective approach for small molecule complexes to induce GPX4-dependent ferroptosis at low-dose photodynamic therapy.

Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNTs. Thus, this work reveals that MNT's carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

However, the scientific literature lacks clear data on the effects of PDT on many of the molecules described, and the available reports are often contradictory. In our work, we highlight the gaps in this knowledge and point to directions for further research that may enhance the efficacy of PDT in the treatment of glioma.

P2, N=20, Recruiting, The Center for Clinical and Cosmetic Research

Some psoriasis treatments, such as psoralen and ultraviolet A (PUVA) therapy and cyclosporine, have been associated with increased risk of skin cancer. Variable data have been reported for anti-tumour necrosis factor (TNF) drugs, whereas other class of biologics, like anti-IL17 and IL23, as well as ustekinumab, seem not to be related to skin cancer risk, such as the case of currently available small molecules.

P1, N=30, Recruiting, Impact Biotech Ltd | Active, not recruiting --> Recruiting

The collaborative action of pyroptosis and ferroptosis generates a synergistic effect that elicits immunogenic cell death, stimulates a robust immune response and effectively inhibits tumor growth in vivo. Our work introduces the first metal-based small molecule dual-inducers of pyroptosis and ferroptosis for potent cancer immunotherapy, and highlights the significance of iron homeostasis as a vital hub connecting synergistic effects of pyroptosis and ferroptosis.

Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32...Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD.

In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy.

P2, N=30, Active, not recruiting, Case Comprehensive Cancer Center | Recruiting --> Active, not recruiting

P2, N=102, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: May 2024 --> Dec 2024

P2, N=25, Not yet recruiting, Mayo Clinic | Trial completion date: Jul 2029 --> Oct 2029 | Initiation date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jul 2029 --> Oct 2029

P1/2, N=19, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=65 --> 19 | Trial primary completion date: Feb 2030 --> Nov 2023

P2, N=15, Terminated, SonALAsense, Inc. | N=40 --> 15 | Trial completion date: Aug 2025 --> Jul 2024 | Active, not recruiting --> Terminated; The study is terminated due to lack of funding but not due to safety concerns.

P3, N=80, Recruiting, Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P3; N=200; Not yet recruiting; Sponsor:Johns Hopkins University

STATEMENT OF SIGNIFICANCE: (1) CNTPA-TPA shared the smallest singlet-triplet energy gap and the largest spin-orbit coupling constant, which boosted intersystem crossing for efficient type-I photodynamic therapy (PDT); (2) Special reactions between cyano groups with glutamate and glutathione in mild conditions restricted the biosynthesis of intracellular GSH. GSH-depletion efficiently induced glutathione peroxidase 4 inactivation and lipid peroxide, resulting in ferroptosis of tumor cells; (3) The combination treatments of ferroptosis-assisted photodynamic immunotherapy induced by single-component CNTPA-TPA with the participation of anti-PD-L1 antibody resulted in increased T-cell infiltration and profound suppression of both primary and distant tumor growth, as well as lung metastasis.

Preclinical studies demonstrate that phytochemicals such as curcumin, psoralen, and dithranol have antipsoriatic effects...This review explores the potential of herbal remedies as a substitute for conventional therapies, emphasizing the clinical trials conducted with these herbal medicines. The paper is supported by the discussion on nanocarriers like liposomes, niosomes, emulsomes, ethosomes, nanostructured lipid carriers, nanoemulsions, and dendrimers that are used to deliver herbal medicines.