Foscan (temoporfin)

Among the tested photosensitizers, zinc phthalocyanine, hypericin, and temoporfin emerged as the top candidates, exhibiting binding energies of - 10.8, - 10.2, and - 9.8 kcal/mol, along with Ki values of 0.012, 0.033, and 0.064 µM, respectively. These compounds outperformed the reference inhibitor ethacrynic acid, which had a binding energy of - 6.6 kcal/mol and a Ki of 14.35 µM. These findings suggest that the dual action of these photosensitizers provides a promising strategy for combating cancer and overcoming treatment resistance.

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.

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.

Therefore, we propose that intracellular localization of GSK3β could be a good marker of response to PDT in HNSCC. Although the molecular mechanism of response to PDT needs further elucidation, this work shows that the most MAL-resistant line of CSCC is more sensitive to Temoporfin.

Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.

Temoporfin, another photodynamic drug, did not show similar activities...Notably, the activity of VP to induce lipid peroxidation was neutralized by ferroptosis inhibitors ferrostatin-1 or liproxstatin-1...These results indicate that VP can induce lipid peroxidation and ferroptosis in the absence of light activation. Our findings reveal a novel mechanism by which VP inhibits tumor growth and provide insights into development of new therapeutic strategies for the treatment of pancreatic cancer.

In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials...PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma...In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments.

The most commonly used photosensitizers include 5-aminolevulinic acid for the enzymatic generation of protoporphyrin IX, Temoporfin-THPC, Photofrin, Hypericin and Talaporfin. An overview of all three generations of photosensitizers is presented. Along with an indication of the limitations of the treatment of brain tumors, intraoperative photodynamic therapy and its possibilities are described as an alternative therapeutic method.

These chlorins have photochemical properties similar to Foscan® but are much more photostable. Among the novel compounds, two chlorins with a hydroxymethyl group and its azide derivative present in the 4,5,6,7-tetrahydropyrazolo&lsqb;1,5-a]pyridine-fused system, are promising photodynamic agents with activity in the 100 nM range against triple-negative breast cancer cells and, in the case of azidomethyl chlorin, a safer phototherapeutic index compared to Foscan®.

Herein, we discuss the use of five photosensitizers in BC models such as chlorin e6 (Ce6), methylene blue, indocyanine green, 5-aminolevulinic acid, and meta-tetra(hydroxyphenyl)chlorin...The PDT search results in animal experiments and its effect on a living organism indicate the possibility of its application in clinical trials on women with local and disseminated BC. The availability and accessibility of small and large BC animal models enable the progress and trial of cancer drugs for innovative technologies and new diagnostics and treatments.

Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2...Hematoporphyrin derivatives, temoporfin, phthalocyanine-4, talaporfin, and chlorine e6 derivatives have mainly been used clinically and preclinically in bile duct cancer...Future human and artificial intelligence collaboration has potential for overcoming challenges related to identifying universal CCA cell targets. This could pave the way for highly targeted therapies for CCA, such as ADC, PDT, and PIT.

Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.

In summary, mTHPC and BU codelivery via nanoparticles efficiently enhances the therapeutic effects of PDT by inhibiting the SRC-3/HIF-1α pathway in CRC. This work provides an effective strategy to combat hypoxia-induced tumour resistance and overcome the barriers of PDT treatment.

In this study, we have shown that the second-generation photosensitizer FOSCAN can be internalized by tumor cells and effectively induce tumor cell death when exposed to laser irradiation in vitro...Moreover, the combination effectively prevented tumor recurrence in vivo through enhanced immune memory T cells after therapy. Therefore, as both are clinically approved techniques, this combination provides a promising strategy for cancer therapy.

Furthermore, we detected mTHPC@VeC/T-RGD NPs mediated PDT sensitizes tumors to PD-L1 blockade therapy mainly because PDT mediated hypoxia could induce HIF-1α signaling pathway that up-regulate PD-L1 expression in CRC. Taken together, our work demonstrates the mTHPC@VeC/T-RGD NPs mediated PDT is a promising strategy, which may potentiate response rate of anti-PD-L1 checkpoint blockade immunotherapies in CRC.

Overall EVs vectorization of mTHPC afforded important tumoral selectivity while overcoming the PDT toxicity of the free drug and prolonged mice survival in the colorectal carcinomatosis model. MSC-EVs produced by our scalable manufacturing method appears like the clinically relevant fourth-generation PDT vehicle to overcome current limitations of PDT in the treatment of peritoneal metastasis and promote a hot tumor immune environment in PM.

Therefore, Foslip® PDT could be a potential treatment for 5-FU resistant cancer patients. Further investigations on the Foslip® PDT mediated molecular changes in HT29FU cells deserve to be explored.

Finally, an in vivo pharmacokinetic study shows that after iv injection, mTHPC incorporated in the P23 micelles displayed prolonged blood circulation kinetics, compared to free mTHPC, independently of the presence of EGa1. Thus, these results make these micelles a promising nanomedicine formulation for selective therapy.