Photodynamic Therapy For Lung Cancer Research Articles

Hydrazone-Functionalized trans-A2B-Corroles: Effective Synergy in Photodynamic Therapy of Lung Cancer.

A synthetic route to trans-A2B-corroles combining the macrocyclic core with a hydrazone moiety, based on the reactivity of azoalkenes toward dipyrromethanes, has been established with the aim of developing a new class of photosensitizers for photodynamic therapy of lung cancer. The study of the photophysical properties of the novel macrocycles allowed the identification of photosensitizers with absorption within the phototherapeutic window and high singlet oxygen quantum yield. Relevant structure-photodynamic activity correlations were established by studying the new corroles-based photodynamic therapy (PDT) in human lung cancer cell lines (A549 and H1299). The methyl-hydrazone corroles were more active than phenyl-hydrazone corroles, with the N-Boc and N-Ts groups being key structural features to ensure high activity. The lead photosensitizers, with IC50 values below 100 nM and no cytotoxicity per se, were significantly more active than 5,10,15-triphenylcorrole, showing that the presence of the hydrazone functional group has a strong influence on PDT activity.

Glutathione-responsive Aggregation-induced Emission Photosensitizers for Enhanced Photodynamic Therapy of Lung Cancer.

Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application.

Bibliometric and visual analysis of photodynamic therapy for lung cancer from 2010 to 2022.

A growing body of research shows that photodynamic therapy (PDT) has become an important mode of treatment in the field of lung cancer (LC) in recent years. Although numerous papers related to PDT in LC have been published, no bibliometric studies have been conducted to summarize the research prospects and highlight the research trends and hotspots in this field. This bibliometric analysis was conducted to investigate and provide a systematic understanding of the development of PDT research for LC over the past 13 years with the aim of providing a reference for new directions and strategies in the field of PDT for LC. In May 2023, relevant publications from the Web of Science Core Collection were downloaded, and CiteSpace and VOSviewer were used to conduct the scientometrics analysis in this study.Results: A total of 2,932 articles and reviews that met the inclusion criteria were retrieved, with China dominated the volume of publications from 2010 to 2022 and the most prolific institution was Shanghai Jiao Tong University. PDT can be utilized for the diagnosis and treat LC. Bronchoscopic fluorescence diagnosis using photosensitizers helps to detect tumor changes in the large bronchial mucosa. In the future, we should actively explore the use of new photosensitizers, including the development of nanomaterials, in addition, PDT combined with other treatments can significantly prolong survival. This combination therapy may also be the direction of future research.

Photodynamic therapy of lung cancer with photosensitizers based on polycationic derivatives of synthetic bacteriochlorin (experimental study)

BackgroundOne of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). MethodsThe anticancer efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against Lewis lung carcinoma were studied in vitro and in vivo. ResultsIt was found that studied PS have high phototoxicity against Lewis lung carcinoma cells: the IC50 values were about 0.8 μM for tetracationic PS and 0.5 μM for octacationic PS. In vivo studies have shown that these PS provide effective inhibition of the tumor growth with an increase in the lifespan of mice in the group by more than 130%, and more than 50% survival of mice in the group. ConclusionsPhotosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high photodynamic efficacy caused by the induction of necrosis and apoptosis of cancer cells, including cancer stem cells, and a sharp decrease of mitotic and proliferative activity. Studied polycationic photosensitizers are much more effective at destroying cancer stem cells and newly formed cancer vessels in comparison with anionic photosensitizers, and ensure the cessation of tumor blood flow without hemorrhages and thrombosis.

Current Status of Photodynamic Therapy for Lung Cancer

Current Status of Photodynamic Therapy for Lung Cancer

Photodynamic therapy of lung cancer, where are we?

Lung cancer remains the leading threat of death globally, killing more people than colon, breast, and prostate cancers combined. Novel lung cancer treatments are being researched because of the ineffectiveness of conventional cancer treatments and the failure of remission. Photodynamic therapy (PDT), a cancer treatment method that is still underutilized, is a sophisticated cancer treatment that shows selective destruction of malignant cells via reactive oxygen species production. PDT has been extensively studied in vitro and clinically. Various PDT strategies have been shown to be effective in the treatment of lung cancer. PDT has been shown in clinical trials to considerably enhance the quality of life and survival in individuals with incurable malignancies. Furthermore, PDT, in conjunction with the use of nanoparticles, is currently being researched for use as an effective cancer treatment, with promising results. PDT and the new avenue of nanoPDT, which are novel treatment options for lung cancer with such promising results, should be tested in clinical trials to determine their efficacy and side effects. In this review, we examine the status and future potentials of nanoPDT in lung cancer treatment.

An update in clinical utilization of photodynamic therapy for lung cancer.

Lung cancer is one of the leading causes of cancer-related death worldwide, with nearly 1.8 million-diagnosis and 1.59 million deaths. Surgery, radiotherapy, and chemotherapy in individual or combination are commonly used to treat lung cancers. Photodynamic therapy (PDT) is a highly selective method for the destruction of cancer cells by exerting cytotoxic activity on malignant cells. PDT has been the subject of numerous clinical studies and has proven to be an effective strategy for cancer therapy. Clinical studies revealed that PDT could prolong survival in patients with inoperable cancers and significantly improve quality of life. For inoperable lung cancer cases, PDT could be an effective therapy. Despite the clinical success reported, PDT is still currently underutilized to treat lung cancer and other tumors. PTD is still a new treatment approach for lung cancer mainly due to the lack of enough clinical research evaluating its' effectiveness and side effects. In this review, we discuss the current prospects and future potentials of PDT in lung cancer treatment.

Targeted nanobody complex enhanced photodynamic therapy for lung cancer by overcoming tumor microenvironment

BackgroundTo investigate the efficacy of a PLGA-based nanobody complex in photodynamic therapy (PDT) and NIR-II imaging in A549 tumor hypoxic model.MethodIR1048-MZ was firstly synthesized by conjugating a nitro imidazole group to IR1048. IR1048-MZ and Cat were then encapsulated in PLGA-SH solution. Anti-EGFR-Nanobody was also expressed and purified, and finally Anti-EGFR-Nanobody@PLGA-IR1048MZ-Cat (Nb@IC-NPs) nanobody complex was obtained based on the formation of desulfide bond between PLGA-SH and Anti-EGFR-Nanobody. Size distribution and morphology were characterized by TEM and DLS. Spectrum of Nb@IC-NPs towards NTR was measured by UV and fluorescence, while the particle’s selective response was studied using fluorescence. The uptake of Nb@IC-NPs in A549 cells was observed by flow cytometry and CLSM. In the meantime, its’ catalytic ability that decomposes H2O2 both extra-and intra-cellular was observed by fluorescence and CLSM. In vitro photodynamic toxicity of Nb@IC-NPs was examined by MTT, Live/Dead Cell Staining, Flow Cytometry and Apoptosis Assay. Tumor-bearing model was constructed to observe a semi-quantitative fluorescent distribution and the possibility of NIR-II fluorescence/photoacoustic (PA) imaging. Effect of Nb@IC-NPs on enhancing A549 tumor hypoxia and expression profile of HIF-1α was investigated in the presence of NIR. An A549 tumor metastasis model was also constructed to confirm the complex’ potential to destroy primary tumor, inhibit lung metastasis, and prolong mice’ survival. Lastly, impact of Nb@IC-NPs on mice’ main organs and blood indices was observed.ResultsNb@IC-NPs was successfully fabricated with good homogeneity. The fluorescent absorbance of Nb@IC-NPs showed a linear relationship with the concentration of NTR, and a higher concentration of NTR corresponded to a stronger photoacoustic signal. In addition, Nb@IC-NPs showed a stable selectivity toward NTR. Our results also suggested a high efficient uptake of Nb@IC-NPs in A549 cells, which was more efficient than IC-NPs and IR1048-MZ alone. In vitro assays confirmed the effects of Nb@IC-NPs on catalytic O2 generation even in hypoxic cells. The cell viability was upregulated with the nanocomplex at the absence of the laser, whereas it was dramatically declined with laser treatment that excited at 980 nm. Nb@IC-NPs achieved tumor hypoxia NIR-II/PA imaging through assisting A549 gathering. When NIR was applied, Nb@IC-NPs can significantly relieve A549 cellular/tumor hypoxia by generating more reactive oxygen species (ROS), which in turn helps lower the expression level of HIF-1α. In summary, Nb@IC-NPs based PDT can efficiently decimate A549 primary tumor, inhibit metastatic lung cancer, and prolong the lifespan of the mice under tolerable dosage. At last, in vivo toxicity tests of the nanocomplex showed its biosafety to the main organs and normal blood indices values.ConclusionNb@IC-NPs improves tumor hypoxia through catalytic reaction and lowers the expression level of HIF-1α. It achieves tumor PA imaging through intensified NIR-II fluorescence signal that caused by response of the complex to the lesion’s nitroreductase (NTR). Nb@IC-NPs based PDT can efficiently kill A549 primary tumor, inhibit a lung metastasis, as well as prolong mice’ survival cycle.

Development and in vitro evaluation of BSA-coated liposomes containing Zn (II) phthalocyanine-containing ferrocene groups for photodynamic therapy of lung cancer

The aim of our study was to discover an alternative active substance to tyrosine kinase inhibitors such as erlotinib (Erlo) used in lung cancer treatment and to develop an appropriate and efficient formulation for oral administration of the substance. Newly synthesized zinc (II) phthalocyanine bearing ferrocene groups (Pc-Zn) was chosen as a model drug due to its use in photodynamic therapy. Pc-Zn increased the amount of nicked form (Form II) by 22.90% and decreased the amount of supercoiled form (Form I) by 77.10% in DNA cleavage studies using plasmid pBR322 DNA in the presence of light and oxygen. Liposome formulations containing Pc-Zn (Pc-Zn Lip) or Erlo (Erlo Lip) had small particle size as 450.5±32.4 nm and 187.2±1.6 nm, respectively and coating with bovine serum albumin (BSA) had not significantly changed particle sizes. Pc-Zn loaded liposomes had significantly (p <0.001) cytotoxic effect under light irradiation than Erlo loaded liposomes. Coating with BSA had no significant effect on the cytotoxicity of the formulations. As a result, it was observed that Pc-Zn was more cytotoxic in the presence of light irradiation than Erlo. However, there was no significant difference in cytotoxic effects between the BSA-coated and non-coated Pc-Zn/Erlo formulations.

RETRACTED ARTICLE: Stem cell membrane–camouflaged bioinspired nanoparticles for targeted photodynamic therapy of lung cancer

Photodynamic therapy (PDT) with photosensitizers has been considered an effective strategy for treating tumors by generating reactive oxygen species (ROS) to induce tumor cells apoptosis or necrosis. However, the poor water solubility, rapid blood clearance, and lack of effective targeting of the photosensitizer are still a serious challenge for its satisfactory anti-cancer efficacy. Herein, we fabricated a stem cell membrane–camouflaged gelatin nanogels (Ng), which integrating the drug loading capacity of Ng and targeting ability of stem cell membrane, endowed with many unique advantages for targeted drug delivery. This bioinspired drug delivery system composed of hydrophobic photosensitizer, chlorin e6 (Ce6)-loaded gelatin nanogels (Ng) (Ng/Ce6), as the inner cores and coated stem cell membrane vesicles (SCV) as the outer shells, noted as Ng/Ce6@SCV. The averaged hydrodynamic diameter of Ng/Ce6@SCV was 202.7 ± 11.7 nm (polydispersity index (PDI) = 0.113). Ng/Ce6@SCV could efficiently promote the cellular internalization of Ce6, and generate enough ROS in the tumor cells after near infrared (NIR) laser irradiation, which could efficiently suppress the growth of A549 tumor cells in vitro. After administration, Ng/Ce6@SCV exhibited targeting accumulation and long-term retention at tumor tissues, which was related to the immune escape and tumor targeting ability of the stem cell membrane. The in vivo anti-tumor activity results also demonstrated the enhanced anti-tumor effect of Ng/Ce6@SCV after NIR irradiation by significantly suppressed the primary tumor growth with minimal side effects. All the results indicated this polyphosphoester-based bioinspired nanodrug delivery system could be a suitable strategy for precise and effective PDT of cancers.

Development of inhalable curcumin loaded Nano-in-Microparticles for bronchoscopic photodynamic therapy

Photodynamic therapy is amongst the most rapidly developing therapeutic strategies against cancer. However, most photosensitizers are administered intravenously with very few reports about pulmonary applications. To address this issue, an inhalable formulation consisting of nanoparticles loaded with photosensitizer (i.e. curcumin) was developed. The nanoparticles were prepared using nanoprecipitation method. Dynamic light scattering measurements of the curcumin loaded nanoparticles revealed a hydrodynamic diameter of 181.20 ± 11.52 nm. In vitro irradiation experiments with human lung epithelial carcinoma cells (A549) showed a selective cellular toxicity of the nanoparticles upon activation using LED irradiating device. Moreover, curcumin nanoparticles exhibited a dose-dependent photocytotoxicity and the IC50 values of curcumin were directly dependent on the radiation fluence used. The nanoparticles were subsequently spray dried using mannitol as a stabilizer to produce Nano-in-Microparticles with appropriate aerodynamic properties for a sufficient deposition in the lungs. This was confirmed using the next generation impactor, which revealed a large fine particle fraction (64.94 ± 3.47%) and a mass median aerodynamic diameter of 3.02 ± 0.07 μm. Nano-in-Microparticles exhibited a good redispersibility and disintegrated into the original nanoparticles upon redispersion in aqueous medium. The Langmuir monolayer experiments revealed an excellent compatibility of the nanoparticles with the lung surfactant. Results from this study showed that the Nano-in-Microparticles are promising drug carriers for the photodynamic therapy of lung cancer.

P1.12-002 Nanoparticle Targeted Folate Receptor 1 Enhanced Photodynamic Therapy for Lung Cancer

Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment is urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer.

Nanoparticle targeted folate receptor 1-enhanced photodynamic therapy for lung cancer

ObjectiveDespite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. Materials and methodsThe frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy. ResultsFOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671nm laser at a dose of 10J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively). Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis. ConclusionFolate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.

SC06.03 Intraoperative Therapies in Malignant Pleural Mesothelioma

SC06.03 Intraoperative Therapies in Malignant Pleural Mesothelioma

Photodynamic Therapy for Lung Cancer

Photodynamic Therapy for Lung Cancer

肺癌における PDT : 現況と将来の展望(内視鏡的治療の立場からみた肺腫瘍の現況と将来)

肺癌における PDT : 現況と将来の展望(内視鏡的治療の立場からみた肺腫瘍の現況と将来)

Hypocrellin B and paclitaxel-encapsulated hyaluronic acid–ceramide nanoparticles for targeted photodynamic therapy in lung cancer

To increase the therapeutic efficacy of photodynamic therapy (PDT) in treating lung cancer, we developed both photosensitizer and anticancer drug encapsulated hyaluronic acid–ceramide nanoparticles. Based on our previous study, a co-delivery system of photosensitizers and anticancer agents greatly improves the therapeutic effect of PDT. Furthermore, hyaluronic acid–ceramide-based nanoparticles are ideal targeting carriers for lung cancer.In vitro phototoxicity in A549 (human lung adenocarcinoma) cells and in vivo antitumor efficacy in A549 tumor-bearing mice treated with hypocrellin B (HB)-loaded nanoparticles (HB-NPs) or hypocrellin B and paclitaxel loaded nanoparticles (HB–P-NPs) were evaluated.Cell viability assay, microscopic analysis and FACS analysis were performed for the in vitro studies and HB–P-NPs showed enhanced phototoxicity compared with HB-NPs. In the animal study, the tumor volume change and the histological analysis was studied and the anticancer efficacy improved in the order of free HB<HB-NPs<HB–P-NPs.In conclusion, the combination therapy of PDT and chemotherapy, and hyaluronic acid–ceramide nanoparticle-based targeted delivery improved the effects of PDT in lung cancer in mice.

Photodynamic Therapy for Lung Cancer and Malignant Pleural Mesothelioma

Photodynamic therapy (PDT) is a form of non-ionizing radiation therapy that uses a drug, called a photosensitizer, combined with light to produce singlet oxygen ((1)O2) that can exert anti-cancer activity through apoptotic, necrotic, or autophagic tumor cell death. PDT is increasingly being used to treat thoracic malignancies. For early-stage non-small cell lung cancer (NSCLC), PDT is primarily employed as an endobronchial therapy to definitively treat endobronchial or roentgenographically occult tumors. Similarly, patients with multiple primary lung cancers may be definitively treated with PDT. For advanced or metastatic NSCLC and small cell lung cancer (SCLC), PDT is primarily employed to palliate symptoms from obstructing endobronchial lesions causing airway compromise or hemoptysis. PDT can be used in advanced NSCLC to attempt to increase operability or to reduce the extent of operation intervention required, and selectively to treat pleural dissemination intraoperatively following macroscopically complete surgical resection. Intraoperative PDT can be safely combined with macroscopically complete surgical resection and other treatment modalities for malignant pleural mesothelioma (MPM) to improve local control and prolong survival. This report reviews the mechanism of and rationale for using PDT to treat thoracic malignancies, details prospective and major retrospectives studies of PDT to treat NSCLC, SCLC, and MPM, and describes improvements in and future roles and directions of PDT.

Our Experience With Photodynamic Diagnosis and Photodynamic Therapy for Lung Cancer

The diagnosis of lung cancer was significantly enhanced by the development of the fiberoptic bronchoscope in 1965. Since then, advances in photosensitizers and light sources have brought photodynamic medicine into the light. This article offers an historic overview of the emergence of photodynamic medicine through the perspective of a pioneer with more than 30 years' experience. Along with a discussion of photodynamic diagnosis of lung cancers via optical coherence tomography, the curative, palliative, and neoadjuvant roles of photodynamic therapy for early and advanced lung cancers are explored. An emerging strategy of using PDM to treat peripheral early-stage lung tumors is briefly discussed.

Targets and Mechanisms of Photodynamic Therapy in Lung Cancer Cells: A Brief Overview

Lung cancer remains one of the most common cancer-related causes of death. This type of cancer typically develops over a period of many years, and if detected at an early enough stage can be eliminated by a variety of treatments including photodynamic therapy (PDT). A critical discussion on the clinical applications of PDT in lung cancer is well outside the scope of the present report, which, in turn focuses on mechanistic and other aspects of the photodynamic action at a molecular and cellular level. The knowledge of these issues at pre-clinical levels is necessary to develop, check and adopt appropriate clinical protocols in the future. This report, besides providing general information, includes a brief overview of present experimental PDT and provides some non-exhaustive information on current strategies aimed at further improving the efficacy, especially in regard to lung cancer cells.