The Effect of Combination of Chemotherapy with Photodynamic Therapy and Surgical Treatment of Breast Cancer on the Structure of the Thymus.

A histological study of structural changes in the thymus of female Wistar rats with chemically induced breast cancer (BC) after photodynamic therapy (PDT) and a combination of PDT and surgical treatment was conducted. After PDT, the thymus showed restoration of the cortical and medullary substance areas, as well as glandular tissue, to the values of the intact control in comparison with the pathological control (BC without treatment). PDT influences both positive and negative selection processes and the activity of T-lymphocyte differentiation processes (the number of epithelial cells and macrophages increases, the number of cells with pyknotic nuclei in the cortical and medullary substance decreases). In the cortico-medullary zone of the thymus, the number of small and medium lymphocytes increases, which may indicate an increase in lymphocyte migration from the thymus. After PDT and subsequent resection of a BC, structural changes in the thymus may indicate a decrease in its lymphopoietic function, activity of both positive and negative T-cell selection processes, as well as a decrease in the activity of T-lymphocyte differentiation processes and their migration from the thymus.

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.

Photodynamic Therapy for Early Stage Central Type of Lung Cancer

Photodynamic Therapy for Urological Malignancies: Past to Current Approaches

Background: IL-12 is a potent cytokine with promising pre-clinical efficacy in solid tumors, including triple-negative breast cancer (TNBC), by enhancing anti-tumor immunity through Treg reprogramming and boosting CD8+ T cell function. However, its clinical use is limited by systemic toxicity and challenges in targeted tumor delivery. Combining IL-12 with photodynamic therapy (PDT) represents a potential solution to these issues, optimizing therapeutic outcomes. Concept & Novelty: We developed a cationic tetra-lipid organic nanoparticle to co-encapsulate IL-12 and HPPH (a photosensitizer; λmax = 658 nm). Efficient IL-12 encapsulation has been challenging due to steric hindrance and hydrophilic nature. To overcome this, we employed a bipolar solvent system (CHCl3:CH3OH, 2:1), achieving 98% IL-12 loading. The self-assembly of IL-12 in methanol enables its complexation with chloroform, forming hydrogen-bonding through synergistic solvation that enhances encapsulation efficiency. Methodology: (a) Liposomal nanoparticle (LNP) Synthesis: The cationic core lumen for IL-12 encapsulation in LNP was achieved by dissolving DPPC, cholesterol, and DOTAP in a 13:5:1 molar ratio in CHCl3. IL-12 (2 mg/mL in CH3OH) was added and stirred for 1 hour. Subsequently, DSPE-PEG-2000-NH2 conjugated with HPPH and DiR in CHCl3 added dropwise and stirred under inert conditions. Solvent removed to form lipid cake (15 mg/L total lipid concentration), and hydrated with PBS. LNP achieved with sonication and multiple freeze/thaw cycles. Purified with centrifugation-dialysis. (b) In-Vivo: 4T1 murine model of breast cancer was developed with 20 Balb/c mice. Double-blind segregation in 5 groups (1 test + 4 control) was done. The test group received intravenous (i.v.) injections of IL-12 and HPPH-loaded LNP (IL-12@LNP-DiR@HPPH) and treated with laser. The control groups received either/or free IL-12/IL-12@LNP-DiR/LNP/No treatment. The biodistribution of LNP was monitored through time-dependent IVIS imaging. Results & Discussion: We synthesized 92 nm IL-12@LNP-DiR@HPPH nanoparticles with surface charge of 0-0.4 mV, indicating stability for biological use. After intravenous injection, maximum DiR fluorescence was observed at tumor site at 6 hours. At this time point, photodynamic therapy with IL-12@LNP-DiR@HPPH resulted in 80-94% tumor volume regression and increased cytolytic T cell presence in the tumor, compared to controls. No toxicity, ulceration, or metastasis was observed in the treatment group during the therapeutic window. Conclusion: We present a novel platform that addresses the challenge of multiple drug loading including efficient loading of IL-12 and successful delivery to the tumor site. A crosstalk between IL-12-mediated immune response and photo-triggered ROS generation promises a potential therapeutic strategy for TNBC with interventions. Citation Format: Sayantan Sinha, Dhruv Bhatnagar, Anne Frei, Heather Himburg, Amit Joshi. Multimodal liposomal organic nanoparticle for immunomodulation and photodynamic combinatorial therapy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4469.

In female Wistar rats with breast cancer, quantitative changes of pro-oncogenic miRNAs (miR-21, -27a, and -221) and tumor-suppressive miR-429 in the mesenteric lymph node were assessed after photodynamic therapy for breast cancer and after photodynamic therapy followed surgical treatment. The level of pro-oncogenic miR-221 in the mesenteric lymph node decreased, and the level of pro-oncogenic miR-21 increased after photodynamic therapy for breast cancer followed by surgical treatment in comparison with the corresponding parameters after photodynamic therapy alone. The content of tumor-suppressive miR-429 remained reduced, as in the group of animals receiving photodynamic therapy alone.

Intrapleural Photodynamic Therapy for Mesothelioma: What Place and Which Future?

Preclinical Study of the Novel Vascular Occluding Agent, WST11, for Photodynamic Therapy of the Canine Prostate

Изменения уровней miR-21, miR-27а, miR-221 и miR-429 в тимусе после фотодинамической терапии и оперативного лечения рака молочной железы у крыс-самок Вистар

Antitumor effect of conditioned media derived from murine MSCs and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer in vitro

PEGylated hydrazided gold nanorods for pH-triggered chemo/photodynamic/photothermal triple therapy of breast cancer

Cancer metastasis after traditional surgery introduces a high barrier to therapy efficacy. Photodynamic therapy (PDT) for cancer is based on a photochemical process of photosensitizers that concentrate in tumors and release oxidant species under light excitation to destroy cells. Compared with traditional surgery, PDT provides minimal invasion and targeted therapy. In this in vivo study, we monitor the real-time and long-term dynamics of circulating tumor cells (CTCs) after a single round of PDT and after surgical resection in a breast cancer animal model. The CTC level is low after PDT treatment, and the recurrence of the primary tumor is postponed in the PDT group compared with the resection group. We find that metastasis is correlated with the CTC level, and the PDT-treated mice show no metastasis in the lung or liver. Our results suggest PDT can effectively reduce metastasis by minimizing CTCs after treatment and is a great technology for breast cancer therapy.

Simple SummaryImmunotherapy has made tremendous clinical progress in breast cancer. However, in some patients, the response rate to immunotherapy is low because the tumor microenvironment (TME) is highly immunosuppressive and the tumors are not sufficiently immunogenic. Photodynamic therapy (PDT) can not only kill tumor cells directly but also induce immunogenic cell death (ICD), which provides antitumor immunity. This review discusses the recent advances in crosstalk between photodynamic therapy and immunotherapy in breast cancer, aiming to provide new perspectives on the treatment of breast cancer.Breast cancer (BC) is the world’s second most frequent malignancy and the leading cause of mortality among women. All in situ or invasive breast cancer derives from terminal tubulobular units; when the tumor is present only in the ducts or lobules in situ, it is called ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS). The biggest risk factors are age, mutations in breast cancer genes 1 or 2 (BRCA1 or BRCA2), and dense breast tissue. Current treatments are associated with various side effects, recurrence, and poor quality of life. The critical role of the immune system in breast cancer progression/regression should always be considered. Several immunotherapy techniques for BC have been studied, including tumor-targeted antibodies (bispecific antibodies), adoptive T cell therapy, vaccinations, and immune checkpoint inhibition with anti-PD-1 antibodies. In the last decade, significant breakthroughs have been made in breast cancer immunotherapy. This advancement was principally prompted by cancer cells’ escape of immune regulation and the tumor’s subsequent resistance to traditional therapy. Photodynamic therapy (PDT) has shown potential as a cancer treatment. It is less intrusive, more focused, and less damaging to normal cells and tissues. It entails the employment of a photosensitizer (PS) and a specific wavelength of light to create reactive oxygen species. Recently, an increasing number of studies have shown that PDT combined with immunotherapy improves the effect of tumor drugs and reduces tumor immune escape, improving the prognosis of breast cancer patients. Therefore, we objectively evaluate strategies for their limitations and benefits, which are critical to improving outcomes for breast cancer patients. In conclusion, we offer many avenues for further study on tailored immunotherapy, such as oxygen-enhanced PDT and nanoparticles.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer associated with poor prognosis and limited treatment options. While chemotherapy has traditionally been the main treatment, resistance frequently emerges, reducing its effectiveness. Recently, a range of immunotherapy strategies, including combinations of chemotherapy and immunotherapy, have expanded treatment possibilities. To further enhance the therapeutic efficacy, there is a desire to combine chemotherapy with other currently used modalities such as photodynamic therapy (PDT) or to encapsulate drugs into nanoparticles (NPs). Ferroptosis has been described as a highly immunogenic type of cell death, characterized by increased ROS and lipid peroxidation. Mesenchymal cancer cells have been reported to be more sensitive to ferroptosis than epithelial cells. We have previously shown that tetraphenylchlorin-conjugated chitosan nanoparticles (TPC-CS NPs) loaded with mertansine and cabazitaxel induce ferroptosis in TNBC.1 In this project, we investigated the effect of TPC-CS NPs together with free RSL3, a ferroptosis inducer. We show that such treatment induces cell death in a mesenchymal breast cancer cell line but not in an epithelial one. The combined treatment also significantly affects lipid peroxidation and mitochondrial function. Based on these results, we encapsulated RSL3 into TPC-CS NPs and used them in two different breast cancer cell lines. We explored the photodynamic effect of empty and RSL3 loaded TPC-CS NPs upon illumination on cell viability by using an MTS assay. Since we have not observed any beneficial effect of TPC-CS NPs-RSL3, we explored the uptake of only empty TPC-CS NPs by using fluorescence microscopy and flow cytometry in these two cell lines. Currently, a biodistribution study in immunocompetent animals bearing 4T1 tumors is being performed. We will perform the maximum tolerable dose experiments for illumination to determine the light dose for further experiments. Moreover, we will perform efficacy studies of TPC-CS NPs and investigate the immune cell composition of tumors and tumor microenvironment using a flow cytometry panel of 25 markers. 1.Pandya AD, Øverbye A, Sahariah P, et al. Drug-Loaded Photosensitizer-Chitosan Nanoparticles for Combinatorial Chemo- and Photodynamic-Therapy of Cancer. Biomacromolecules. 2020/04/13 2020;21(4):1489-1498. This project has received funding from the Europe Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 956544. Citation Format: Marek Feith, Abhilash D. Pandya, Astrid Hyldbakk, Anders Høgset, Kirsten Sandvig, Tore Skotland, Tore-Geir Iversen, Gunhild Mari Mælandsmo. Photodynamic therapy in breast cancer by photosensitizer-chitosan particles inducing ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4483.

The low X-ray attenuation coefficient of tumor soft tissue and the hypoxic tumor microenvironment (TME) during radiation therapy (RT) of breast cancer result in RT resistance and thus reduced therapeutic efficacy. In addition, immunosuppression induced by the TME severely limits the antitumor immunity of radiation therapy. In this paper, we propose a PCN-224@IrNCs/D-Arg nanoplatform for the synergistic radiosensitization, photodynamic, and NO therapy of breast cancer that also boosts antitumor immunity (PCN = porous coordination network, IrNCs = iridium nanocrystals, D-Arg = D-arginine). The local tumors can be selectively ablated via reprogramming the tumor microenvironment (TME), photodynamic therapy (PDT) and NO therapy, and the presence of the high-Z element Ir that sensitizes radiotherapy. The synergistic execution of these treatment modalities also resulted in adapted antitumor immune response. The intrinsic immunomodulatory effects of the nanoplatform also repolarize macrophages toward the M1 phenotype and induce dendritic cell maturation, activating antitumor T cells to induce immunogenic cell death as demonstrated in vitro and in vivo. The nanocomposite design reported herein represents a new regimen for the treatment of breast cancer through TME reprogramming to exert a synergistic effect for effective cancer therapy and antitumor immunity.