• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.9-16
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• 2023

Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of ⁶⁴Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that ⁶⁴Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

• Journal of Life Science
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• v.33 no.2
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• pp.158-168
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• 2023

Natural products have been used to mitigate the effects of cancer and infectious diseases, as they feature diverse bioactivities, such as antioxidant, antibacterial, anti-inflammatory, and immunomodulatory effects. Here, we chose 10 natural products that are well-known as pulmonary enhancers and investigated their bactericidal effects on Streptococcus pneumoniae. In the disk diffusion assay, the growth of S. pneumoniae was significantly regulated by G. fructus treatment regardless of extraction method used. We first adopted spraying as a novel delivery method for G. fructus. Interestingly, mice exposed to G. fructus three times a day for 2 weeks were resistant to S. pneumoniae intranasal infection (shown both through body weight loss and survival rates compared to the control group). Moreover, we confirmed that exposure to G. fructus regulated the colonization of the bacteria despite the sustained inflammation in the lung after exposure to S. pneumoniae, indicating that migrated inflammatory immune cells may involve a host defense mechanism against pulmonary infectious diseases. While a similar number of granulocytes (CD11b⁺Ly6C⁺Ly6G⁺), neutrophils (CD11b⁺Ly6C^intLy6G⁺), and monocytes (CD11b⁺Ly6C^intLy6G^-) were found between groups, a significantly increased number of alveolar macrophages (CD11b⁺CD11c^hiF4/80⁺) was detected in BAL fluids of mice pre-exposed to G. fructus at 5 days after S. pneumonia infection. Taken together, our data suggest that this usage of G. fructus can induce protective immunity against bacterial infection, indicating that facial spray may be helpful in enhancing the defense mechanism against pulmonary inflammation and in evaluating the efficacy of natural products as immune enhancers against respiratory diseases.

• Journal of the Korean Society of Radiology
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• v.82 no.2
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• pp.371-381
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• 2021

Purpose To evaluate the usefulness and effectiveness of bronchial occluders in the treatment of postoperative bronchopleural fistula (BPF). Materials and Methods The subjects of the study were six out of seven postoperative BPF patients who underwent surgery due to tuberculosis or lung cancer between 2009 and 2019. Each patient had a bronchial occluder inserted to treat BPF that occurred after surgery. Of the six patients, five had lung cancers and one had tuberculosis. Five were male and one was female; their ages ranged from 59 to 74 years, with an average of 69 years. The diagnosis of BPF was based on findings from bronchoscopy and CT, and treatment was initiated approximately 1 to 2 weeks after diagnosis. The technical and clinical success of the bronchial occluders in the treatment of BPF was evaluated. The study assessed the postoperative clinical effects of the occluders, survival duration, and additional treatments. Results All six patients were successfully treated. Clinical success was achieved in five patients, while partial clinical success was achieved in one; there was no clinical failure. No complications during the migration of the device or device perforations were observed. Two patients were diagnosed with BPF by CT, while four were diagnosed by bronchoscopy. Lobectomy, bilobectomy, and pneumonectomy were performed on two patients each. The periods between surgery and diagnosis ranged from 1 to 34 months; the average was 10 months. Four patients (59-103 days; an average of 80.5 days) died and two (313 days, 3331 days) survived. The causes of death were aggravation of the underlying disease (n = 2), pulmonary edema and pleural effusion (n = 1), and pneumonia (n = 1). Additional catheter drainage was performed in one patient, and a chest tube was maintained in two patients. Conclusion Bronchial occluders are useful and effective in the treatment of BPF after pulmonary resection.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.37-53
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• 1998

The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.