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CARBOHYDRATE RESEARCH · 2024 · IF 2.4

Sensitive, precise fingerprint profiling for monosaccharide analysis of Bacillus Calmette-Guérin polysaccharide and nucleic acid isolates

Lan Luo,Lisha Lin,Sheng Huang,Yunxi Zhou,Shengmei Yang,Yan Zhu,Lanyan Zhang,Donghua Xiong,Yongsheng Wu,Mingyi Wu

A sensitive and precise HPLC-DAD method with pre-column PMP derivatization was established and validated, for analyzing the polysaccharides in Bacillus Calmette-Guérin polysaccharide and nucleic acid (BCG-PSN) isolates, after acid hydrolysis. And the HPLC fingerprint profiling was used to analyze its monosaccharide composition. The monosaccharide concentration-peak area calibration curve was of good linearity (R 2  > 0.99), over the range of 0.016–0.08 mg/mL for mannose or 0.24–1.20 mg/mL for glucose, with high recovery of 93–105 % for quality control samples. The intra-day RSD values of mannose and glucose concentration were less than 2.5 % and 2.1 %, respectively, and their inter-day RSD values were less than 4.3 % and 2.2 %, respectively, and remained stable for up to 14 days. This method also remained durable against changes in chromatographic parameters, but it's susceptible to the flow rate of mobile phase. Additionally, the method was applied to analyze the content of mannose and glucose in 22 batches BCG-PSN powder and 17 batches BCG-PSN injection. The results showed that the HPLC-DAD fingerprint spectra of all the BCG-PSN powder and BCG-PSN injection samples had a high degree of similarity, with the similar indexes up to 0.999 and 0.998, respectively. The HPLC-DAD method with pre-column PMP derivatization is highly rapid, effective, visual, and accurate for determination of monosaccharide contents. The validated method was successfully applied to the analysis of polysaccharide in both BCG-PSN powder and injection.

CAS / MDL: 89-25-8
研究领域: 生物化学 · 药物分析 · 医学
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ACS Nano · 2025 · IF 16

Prolonged Release of Bacillus Calmette–Guérin by Floating Microbubbles to Enhance Intravesical Immunotherapy for Bladder Cancer

Tianmin Tang,Shuying Kong,Junyi Xie,Qiurong Deng,Cong Lai,Shuanshuan Guo,Hao Yu,Jianhua Zhou

Intravesical Bacillus Calmette–Guérin (BCG) immunotherapy is a standard treatment for intermediate-risk and high-risk nonmuscle-invasive bladder cancer. The prolonged duration of BCG in the bladder can enhance the immunotherapeutic efficacy. However, intravesical BCG is rapidly excreted with urine by urination at 2 h postinstillation, compromising therapeutic outcomes. Here, this study develops a floating drug delivery system based on air microbubbles to achieve long-term retention of BCG in the bladder. By encapsulating BCG within floating air microbubbles, we successfully develop BCG-loaded microbubbles (BCG-MBs) that are capable of prolonged release of BCG in the bladder. Compared with conventional intravesical BCG immunotherapy, intravesical instillation of BCG-MBs induces more durable immune responses and demonstrates enhanced therapeutic efficacy in SD rats with orthotopic bladder cancer. Furthermore, the floating drug delivery system based on air-microbubbles not only represents a potential intravesical drug carrier for bladder cancer, but also a versatile platform that can encapsulate diverse therapeutic agents, thereby showing great potential applications in immunotherapy, targeted drug delivery, and combination therapy.

研究领域: 免疫治疗 · 药物递送 · 泌尿学 · 癌症研究 · 生物医学工程
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Cell Reports Medicine · 2025 · IF 10.6

BET inhibitor in combination with BCG vaccine enhances antitumor efficacy and orchestrates T cell reprogramming for melanoma

Wenhua Wang,Xin Li,Rui Hu,Liang Dong,Shiyao Pei,Liping Jin,Qian Gao,Xiang Chen,Mingzhu Yin

Immunotherapy shows remarkable benefits in treating melanoma, yet existing approaches achieve limited overall responses. Here, we show that a combination of bromodomain and extra-terminal protein family inhibitor, NHWD-870, and Bacillus Calmette-Guérin vaccine is a promising therapeutic strategy for melanomas. Single-cell transcriptome analyses and functional experiments show that the combination therapy significantly inhibited tumor growth by reprogramming T cells toward an immune-activated state, enhancing their cytotoxicity, preventing their exhaustion, and increasing the recruitment of them into the tumor microenvironment. We identify the molecule, MT1, as a direct downstream target of BRD4, which is effectively suppressed by NHWD-870. Furthermore, our findings are reinforced by a humanized patient-derived xenograft (PDX) model, which exhibits notable antitumor effects in humanized tumor-bearing mice treated with the combination therapy. Our study underscores the immense potential of this therapeutic approach for clinical practice, offering promising prospects in overcoming the limitations of current treatments.

CAS / MDL: 8001-30-7
研究领域: 肿瘤学 · 免疫学 · 分子生物学 · 癌症治疗
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NANOTECHNOLOGY · 2023 · IF 3.5

Application of microneedles combined with dendritic cell-targeted nanovaccine delivery system in percutaneous immunotherapy for triple-negative breast cancer

Jiaqi Weng,Jing Yang,Weiwei Wang,Jiaoli Wen,Min Fang,Gensuo Zheng,Jing Xie,Xi Zheng,Qinying Yan,Lili Feng

This work aims at developing a strategy to activate the antigen-presenting cells to enhance the effect of immunotherapy in triple-negative breast cancer (TNBC) through the dissolving microneedle patch (DMNP). In the compound adjuvant nanovaccine system, mannosylated chitosan (MCS) nanoparticles (NPs) were designed to target dendritic cells (DCs), and the immunotherapy effect was enhanced by the adjuvant Bacillus Calmette-Guerin polysaccharide (BCG-PSN), achieving the purpose of transdermal immunotherapy for TNBC. Vaccination studies in mice demonstrated that MCS NPs effectively induce DCs maturation in the tumor-draining lymph nodes to stimulate strong immune responses in TNBC. Overall, chitosan-based DMNPs with complex adjuvant constituted a new potent transdermal vaccine delivery platform capable of exploiting more dendritic cells in the skin for effective immunization.

研究领域: 癌症免疫疗法 · 纳米技术 · 药学 · 生物医学工程
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Anti-Cancer Agents in Medicinal Chemistry · 2020 ·Vol. 20 ·期 13 ·1571-1581 · IF 2.049

The Apoptosis Mechanism of Epirubicin Combined with BCG on Human Bladder Cancer Cells

Luo Yang,Fu Xiaoyi,Han Bin,Zhang Fafu,Yuan Lihong,Men Hongsheng,Zhang Shulin,Tian Sujuan,Dong Bin,Meng Minjie

Aims: The purpose of our study was to explore the combination effect of epirubicin and Bacillus Calmette Guerin (BCG) and its mechanism. Background: Bladder cancer is a threat to human health worldwide. Commonly used chemotherapy drugs and biotherapy have significant therapeutic effects on bladder cancer, but the mechanism and combined effects are still unclear. Objective: To evaluate the anti-cancer effect of epirubicin combined with BCG on human bladder cancer cells, our studies were carried out. Methods: The viability of human bladder cancer cells with epirubicin and/or BCG treatments was examined by Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma 2 (Bcl-2) were detected by western blot. Results: The viability of human bladder cancer with epirubicin or BCG treatment was decreased and the viability with epirubicin combined with BCG treatment was decreased more, which were determined by CCK-8 assay. Both epirubicin and BCG increased the apoptosis rate of human bladder cancer and arrested more cells into G0/G1 phase, which were tested by flow cytometry. The expression of caspase-3, p53 and Bax was increased and the expression of Bcl-2 was decreased with epirubicin treatment on human bladder cells, which were analyzed by western blot. The expression of caspase-3 and p53 was increased with BCG treatment, which was examined by western blot. Conclusion: Epirubicin induced apoptosis in human bladder cancer cells by up-regulating the expression of proapoptotic factors (caspase-3, p53 and Bax) and down-regulating the expression of anti-apoptotic factor (Bcl-2). BCG promoted apoptosis of human bladder cancer cells by up-regulating the expression of caspase-3 and p53. BCG plays a potential role at the time of the combination of epirubicin and BCG on bladder cancer cells in early stage. Both epirubicin and BCG affected cell cycle distribution via arresting more bladder cancer cells at G0/G1 phase, which ultimately led bladder cancer proliferation in vitro and promoted apoptosis.

研究领域: 肿瘤学 · 药理学 · 分子生物学 · 细胞生物学
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ADVANCED MATERIALS · 2024 · IF 27.4

Drug-Loaded Bacillus Calmette–Guérin Bacteria for Immuno-Chemo Combo Therapy in Bladder Cancer

Kangkang Liu,Lining Wang,Jing Peng,Yuanji Lyu,Yiming Li,Dengyi Duan,Wenyi Zhang,Guojiang Wei,Taipeng Li,Yuanjie Niu,Yang Zhao

Intravesical Bacillus Calmette–Guérin (BCG) is a well-established strategy for managing high-risk nonmuscle-invasive bladder cancer (NMIBC); however, over half of patients still experience disease recurrence or progression. Although the combined intravesical instillation of various chemotherapeutic drugs is implemented in clinical trials to enhance the BCG therapy, the outcome is far from satisfying due to severe irritative effects and treatment intolerance at high doses. Therefore, it is adopted the “biotin–streptavidin strategy” to doxorubicin (DOX)-encapsulated nanoparticles within live BCG bacteria (DOX@BCG) to improve treatment outcomes. Adherence of BCG to the bladder epithelium helps precisely target DOX@BCG to the local tumor cells and simultaneously increases intratumoral transport of therapeutic drugs. DOX@BCG effectively inhibits cancer progression and prolongs the survival of rats/mice with orthotopic bladder cancer owing to synergism between BCG-immunotherapy, DOX-chemotherapy, and DOX-induced immunogenic tumor cell death; furthermore, it exhibits improved tolerance and biosafety, and establishes antitumor immunity in the tumor microenvironment. Therefore, the drug-loaded live BCG bacterial delivery system holds considerable potential for clinical translation in the intravesical treatment of bladder cancer.

CAS / MDL: 684-93-5 3817-11-6
研究领域: 肿瘤学 · 药理学 · 免疫治疗 · 纳米技术 · 癌症研究
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