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Near infrared light-responsive heat-emitting hemoglobin hydrogels for photothermal cancer therapy
摘要： Photothermal therapy (PTT) is an effective means of treating tumors because tumor cells are sensitive to heat. Gold and carbon nanoparticles are used as efficient PTT materials. However, development of a non-toxic biodegradable PTT agent remains a challenge. Here, we developed a hemoglobin (Hb) hydrogel that exhibited excellent PTT effects in vitro and in vivo. Unlike conventional PTT agents, which are toxic and do not decompose completely in the body, the Hb hydrogel was manufactured using only two components: (i) Hb, a natural substance derived from the human body, and (ii) PEG, an FDA-approved polymer. The gelation time of the Hb hydrogels could be controlled by changing the Hb concentration. Because Hb is present at a high concentration (150 mg/ml) in the body, the Hb hydrogel decomposed and was eliminated in vivo without toxicity. The Hb hydrogel showed an excellent PTT effect in response to 808 nm near-infrared (NIR) laser irradiation and had excellent anticancer effects against A549 lung cancer cells both in vitro and in vivo. Blood hematology and blood biochemical assay results from an animal model treated with Hb hydrogel were similar to those of the control group. Importantly, toxicity was not observed based on H&E staining of major organs (heart, liver, spleen, kidneys and lung). Tumors of A549 cell-xenografted mice treated with Hb hydrogel and 808 nm NIR laser irradiation were significantly smaller than those of the control group (23.1 mm3 versus 746.5 mm3, respectively). This is a first report of a biocompatible photothermal hydrogel based on hemoglobin, and our overall results suggest that Hb hydrogels are commercially-promising PTT systems that have excellent anti-cancer effects.
关键词： Biocompatibility,Quick gelation,Lung cancer,Hemoglobin,Hydrogel,Photothermal therapy
更新于2025-09-23 15:23:52
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Porphyrin–High-Density Lipoprotein: A Novel Photosensitizing Nanoparticle for Lung Cancer Therapy
摘要： Background. We have developed ultrasmall porphyrin–high-density lipoprotein (HDL) nanoparticles (<20 nm), called “porphyrinHDL,” that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become ?uorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted to scavenger receptor class B type I (SR-BI) expressed on lung cancer cells as a ?rst step toward development of a minimally invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. Methods. The in vitro uptake of porphyrinHDL and the corresponding PDT ef?cacy were evaluated in both SR-BI–positive and SR-BI–negative lung cancer cell lines. A clinically relevant orthotopic lung cancer model in mice was used to examine ?uorescence activation and quanti?cation of uptake in tumor. In addition, we investigated the effect of porphyrinHDL-mediated PDT. Results. PorphyrinHDL promoted proper intracellular uptake in the H460 human lung cancer cell line. When irradiated with a 671-nm PDT laser, porphyrinHDL produced signi?cant therapeutic effectiveness in vitro. After systemic administration in mice with orthotopic lung cancer xenografts, porphyrinHDL demonstrated selective accumulation and photoactivation in tumor with signi?cantly enhanced disease-to-normal tissue contrast. Moreover, porphyrinHDL-PDT signi?cantly induced cell apoptosis in lung tumors (73.2%) without toxicity in normal tissues or damage to adjacent critical structures. Conclusions. SR-BI–targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a “smart” PDT approach for highly selective tumor ablation.
关键词： Nanoparticles,PorphyrinHDL,Lung cancer,Scavenger receptor class B type I,Photodynamic therapy
更新于2025-09-23 15:23:52
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Identification and imaging of miR-155 in the early screening of lung cancer by targeted delivery of octreotide-conjugated chitosan-molecular beacon nanoparticles
摘要： Lung cancer is still the most common cancer globally. Early screening remains the key to improve the prognosis of patients. There is currently a lack of specific and sensitive methods for early screening of lung cancer. In recent years, studies have found that microRNA plays an important role in the occurrence and development of lung cancer and become a biological target in the early diagnosis of lung cancer. In this study, lung cancer cells, subcutaneous xenografts of lung cancer in nude mice, and Lox-Stop-lox K-ras G12D transgenic mice were used as models. The transgenic mice displayed the dynamic processes from normal lung tissue to atypical hyperplasia, adenomas, carcinoma in situ and lung adenocarcinoma. It was found that miR-155 and somatostatin receptor 2 (SSTR2) were expressed in all the disease stages of transgenic mice. Through molecular beacon (MB) technology and nanotechnology, chitosan-molecular beacon (CS-MB) nanoparticles and targeted octreotide (OCT) were conjugated and synthesized. The octreotide-conjugated chitosan-molecular beacon nanoparticles (CS-MB-OCT) can specifically bind to SSTR2 expressed by the lung cancer cells to achieve the goal of identification of lung cancer cells and imaging miR-155 in vivo and in vitro. Fluorescence imaging at different disease stages of lung cancer in Lox-Stop-lox K-ras G12D transgenic mice was performed, and could dynamically monitor the occurrence and development of lung cancer by different fluorescence intensity ranges. The current research, in turn, provides new idea, new method, and new technology for the early screening of lung cancer.
关键词： chitosan nanoparticles,molecular imaging,molecular beacon,Lung cancer,microRNA-155
更新于2025-09-23 15:23:52
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Expression of peptide transporter 1?has a positive correlation in protoporphyrin IX accumulation induced by 5-aminolevulinic acid with photodynamic detection of non-small cell lung cancer and metastatic brain tumor specimens originating from non-small cell lung cancer
摘要： BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be an useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors. METHODS: Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors. RESULTS: A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009). CONCLUSION: Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC.
关键词： protoporphyrin IX,brain metastasis,non-small lung cancer,peptide transporter 1
更新于2025-09-23 15:22:29
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In Vivo imaging characterization and anticancer efficacy of a novel HER2 Affibody and Pemetrexed conjugate in lung Cancer model
摘要： Introduction: In this study, a new agent consisting of HER2-specific affibody ZHER2:V2 and chemotherapy drug pemetrexed was synthesized to develop a new targeted drug. Its biological characteristics and anticancer efficacy were assessed in cells level and xenografts models by radiolabeling with technetium-99m. Methods: After the ZHER2:V2-pemetrexed conjugate was synthesized, radiolabeling of the conjugate was performed using its C-terminal 4 amino acids (Gly-Gly-Gly-Cys) as the chelating moiety. The radiochemical yield of the [99mTc]Tc-ZHER2:V2-pemetrexed was identified by instant thin-layer chromatography (ITLC). Stability of the radiolabeled conjugate was investigated both in vitro and in vivo. In vitro binding affinity and cell internalization study of the probe were performed in A549 cells (HER2-positive). Tumor uptake was evaluated by in vitro uptake assay in A549 cells and H23 cells (HER2-negative), and by in vivo biodistribution and SPECT imaging in A549 and H23 tumor-bearing mice. The antitumor efficacy of the ZHER2:V2-pemetrexed conjugate was evaluated in cells and xenograft models. Results: The ZHER2:V2-pemetrexed was successfully synthesized and conjugated with technetium-99m, and acquired the radiochemical yield of 97.0 ± 0.3%. The stability of [99mTc]Tc-ZHER2:V2-pemetrexed was good in both physiological saline and human serum. The radiolabeled agent displayed excellent HER2-binding specificity and affinity in vitro ， and was gradually internalized into the cells. Biodistribution study revealed obvious tumor uptake in A549 xenografts (percentage injected dose per gram, 2.6 ± 1.0 %ID/g at 4 h postinjection), while the uptake in HER2-negative H23 tumors was much lower (0.2 ± 0.1 %ID/g at 4 h postinjection, P < 0.01). SPECT imaging exhibited an intensity in the A549 xenograft which could be blocked by excess ZHER2:V2-pemetrexed. Treatment with ZHER2:V2-pemetrexed significantly impaired the tumor growth (P < 0.05), with less weight loss than pemetrexed. Conclusion: [99mTc]Tc-ZHER2:V2-pemetrexed showed desirable property and HER2-specificity. The ZHER2:V2-pemetrexed conjugate could inhibit tumor growth of HER2-positive lung adenocarcinoma and may have the potential to become a targeted drug for lung cancer. Advances in knowledge and implications for patient care: The compound described herein performs HER2-targeting with favorable anticancer efficacy and offers the potential of novel targeting strategies for further tumor therapy.
关键词： pemetrexed,lung cancer,radionuclide imaging,HER2
更新于2025-09-23 15:21:21
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Lung Cancer - Strategies for Diagnosis and Treatment || Targeted Photodynamic Therapy for Improved Lung Cancer Treatment
摘要： Cancer develops from the outgrowth of a clonal population of cells with a genetic pathology to evade cell death and exponential proliferation. It has become a global burden with increasing mortality rates. Lung cancer is a major contributor to cancer fatalities. Conventional therapies have shown advances in treating lung cancer, but the successful eradication of cancer lies in targeting both cancer and cancer stem cells. Cancer stem cells (CSCs) are a ration of cells found within the tumour bulk, capable of cancer initiation, therapy resistance, metastasis and cancer relapse. Photodynamic therapy (PDT) has proven effective in treating lung cancer. PDT exerts selective cell death mechanisms toward cancerous cells. With the use of a photosensitizer (PS) which becomes excited upon irradiation with laser light at a specific wavelength, the PS forms reactive oxygen species (ROS) in turn killing neoplastic cells. Leading therapeutic sequel can be obtained by transcending PDT though combination therapies such as immunotherapy and nanotechnology which will enable PDT to target lung CSCs preventing lung cancer recurrence.
关键词： lung cancer stem cells,targeted PDT,lung cancer,PDT
更新于2025-09-23 15:21:01
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Clinical trial of photodynamic therapy for peripheral-type lung cancers using a new laser device in a pilot study
摘要： Introduction/Aim: Photodynamic therapy (PDT) involves the use of a tumor-specific photosensitizer and laser irradiation, and one of the treatment options recommended for early centrally located lung cancers, but not yet for peripheral-type lung cancers. We developed a new laser probe, the composite-type optical fiberscope (COF), which allows accurate laser irradiation of a cancer lesion with simultaneous visualization of the lesion. Methods: This phase I study was conducted in 7 patients with peripheral lung cancers (primary tumor ≤20 mm in diameter). We performed endobronchial PDT for these patients using the new laser probe and talaporfin sodium as the photosensitizer. Results: We performed PDT for 3 patients with peripheral lung cancer using a laser dose of 50 J/cm2 at 120 mW, and confirmed the feasibility of using this dose. Then, we escalated the laser dose to 100 J/cm2 in 4 additional patients. A total of 7 patients met our inclusion criteria. Evaluation at 2 weeks and 3 months after the PDT revealed no complication such as pneumonia or pneumothorax. At the evaluation conducted 6 months later, we found CR in 3 cases and SD in the remaining 4 cases. Conclusion: PDT was found to be a feasible and non-invasive treatment modality for early peripheral-type lung cancer. In the future, PDT could become a standard treatment option for peripheral-type lung cancer.
关键词： Photodynamic Therapy (PDT),laser,peripheral type lung cancer,clinical trial,photosensitizer,endobronchial treatment
更新于2025-09-23 15:21:01
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Variability and repeatability of quantitative uptake metrics in [ <sup>18</sup> F]FDG PET/CT imaging of non-small cell lung cancer: impact of segmentation method, uptake interval, and reconstruction protocol
摘要： OBJECTIVES: There is increased interest in various new quantitative uptake metrics beyond standardized uptake value (SUV) in oncology PET/CT studies. The purpose of this study is to investigate the variability and test-retest repeatability (TRT) of metabolically active tumor volume (MATV) measurements and several other new quantitative metrics in non-small cell lung cancer (NSCLC) using [18F]FDG PET/CT with different segmentation methods, user interactions, uptake intervals, and reconstruction protocols. METHODS: Ten advanced NSCLC patients received two whole-body [18F]FDG PET/CT scans at both 60 and 90 min post-injection. PET data were reconstructed with four different protocols. Eight segmentation methods were applied to delineate lesions with and without a tumor mask. MATV, maximum and mean SUV (SUVmax, SUVmean), total lesion glycolysis (TLG), and intralesional heterogeneity features were derived. Variability and repeatability were evaluated using a generalized estimating equations statistical model with Bonferroni correction for multiple comparisons. The statistical model, including interaction between uptake interval and reconstruction protocol, was applied individually to the data obtained from each segmentation method. RESULTS: Without masking, none of the segmentation methods could delineate all lesions correctly. MATV was affected by both uptake interval and reconstruction settings for most segmentation methods. Similar observations were obtained for the uptake metrics SUVmax, SUVmean, TLG, homogeneity, entropy, and zone percentage. No effect of uptake interval was observed on TRT metrics, while the reconstruction protocol affected the TRT of SUVmax. Overall, segmentation methods showing poor quantitative performance in one condition showed better performance in other (combined) conditions. For some metrics, a clear statistical interaction was found between the segmentation method and both uptake interval and reconstruction protocol. CONCLUSIONS: All segmentation results need to be reviewed critically. MATV and other quantitative uptake metrics, as well as their TRT, depend on segmentation method, uptake interval, and reconstruction protocol. To obtain quantitative reliable metrics, with good TRT performance, the optimal segmentation method depends on local imaging procedure, the PET/CT system and/or reconstruction protocol. Rigid harmonization of imaging procedure and PET/CT performance will be helpful in mitigating this variability.
关键词： non-small cell lung cancer,segmentation method,positron emission tomography imaging,repeatability,Variability
更新于2025-09-23 15:21:01
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Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial
摘要： With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer.
关键词： chemoradiotherapy,Imaging-based target volume reduction,randomised,multicentre,controlled trial,open-label,PET-Plan,locally advanced non-small-cell lung cancer
更新于2025-09-23 15:19:57
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Fluorometric immunoassay for the simultaneous determination of the tumor markers carcinoembryonic antigen and cytokeratin 19 fragment using two kinds of CdSe/ZnS quantum dot nanobeads and magnetic beads
摘要： A method is described for the simultaneous determination of the carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1). Two kinds of CdSe/ZnS quantum dot nanobeads (QBs), with emission maxima at 530 nm (green) and 585 nm (yellow), were used as labels, and magnetic beads (MBs) for separation. The MBs were used as substrates to couple CEA and CYFRA21-1 antibody for isolating the proteins. Then, the differently colored QBs were linked to the antibodies against CEA and CYFRA21-1, respectively. Following the formation of the immunocomplex, the intensities of the green and yellow emissions were measured at the same excitation wavelength of 340 nm. The detection limits are 0.1 ng·mL?1 for CEA, and of 0.2 ng·mL?1 for CYFRA21-1. The recoveries from spiked serum are 92.1 - 118.1% for CEA, and from 90.8% to 115.2% for CYFRA21-1, with the relative standard deviations of 6.3 - 12.3% and 7.1 - 11.8%. The method was successfully applied to the simultaneous determination of the two proteins in human serum sample (n = 45). The results correlated well with those of the chemiluminescent enzyme immunoassay kit.
关键词： Lung cancer,Human serum,Fluorescence,Multiplexed detection,Antibody
更新于2025-09-23 15:19:57