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

ABSTRACT: 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.

SUBMITTER: Wang K

PROVIDER: S-EPMC7797657 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Wang Kai K Yu Boxin B Pathak Janak L JL

Journal of Cancer 20210101 4

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 ther ...[more]

PMID: 33442413

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Project description:PurposeTo provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non-small-cell lung cancer (NSCLC).MethodsAn Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014.ResultsThis guideline update reflects changes in evidence since the previous guideline.RecommendationsThere is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is recommended. There are insufficient data to recommend routine third-line cytotoxic therapy. Decisions regarding systemic therapy should not be made based on age alone. Additional information can be found at http://www.asco.org/guidelines/nsclc and http://www.asco.org/guidelineswiki.

Project description: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.

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

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

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