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Drug-Loaded Bacillus Calmette–Guérin Bacteria for Immuno-Chemo Combo Therapy in Bladder Cancer
Advanced Materials ( IF 27.4 ) Pub Date : 2024-02-08 , DOI: 10.1002/adma.202310735
Kangkang Liu 1 , Lining Wang 1 , Jing Peng 2 , Yuanji Lyu 2 , Yiming Li 2 , Dengyi Duan 2 , Wenyi Zhang 2 , Guojiang Wei 1 , Taipeng Li 1 , Yuanjie Niu 1 , Yang Zhao 2
Advanced Materials ( IF 27.4 ) Pub Date : 2024-02-08 , DOI: 10.1002/adma.202310735
Kangkang Liu 1 , Lining Wang 1 , Jing Peng 2 , Yuanji Lyu 2 , Yiming Li 2 , Dengyi Duan 2 , Wenyi Zhang 2 , Guojiang Wei 1 , Taipeng Li 1 , Yuanjie Niu 1 , Yang Zhao 2
Affiliation
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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.
中文翻译：
用于膀胱癌免疫化疗联合治疗的载药芽孢杆菌
膀胱内注射卡介苗 (BCG) 是治疗高风险非肌层浸润性膀胱癌 (NMIBC) 的成熟策略；然而，超过一半的患者仍然出现疾病复发或进展。尽管在临床试验中采用多种化疗药物联合膀胱灌注来增强卡介苗治疗，但由于高剂量时的严重刺激作用和治疗不耐受，结果远不能令人满意。因此，采用“生物素-链霉亲和素策略”将阿霉素（DOX）封装在活卡介苗细菌（DOX@BCG）内的纳米颗粒来改善治疗效果。 BCG 与膀胱上皮的粘附有助于将 DOX@BCG 精确靶向局部肿瘤细胞，同时增加治疗药物的肿瘤内转运。由于 BCG 免疫疗法、DOX 化疗和 DOX 诱导的免疫原性肿瘤细胞死亡之间的协同作用，DOX@BCG 有效抑制癌症进展并延长原位膀胱癌大鼠/小鼠的生存期；此外，它表现出更好的耐受性和生物安全性，并在肿瘤微环境中建立抗肿瘤免疫力。因此，载药活卡介苗细菌递送系统在膀胱癌膀胱内治疗中具有巨大的临床转化潜力。
更新日期：2024-02-08
中文翻译：
用于膀胱癌免疫化疗联合治疗的载药芽孢杆菌
膀胱内注射卡介苗 (BCG) 是治疗高风险非肌层浸润性膀胱癌 (NMIBC) 的成熟策略；然而，超过一半的患者仍然出现疾病复发或进展。尽管在临床试验中采用多种化疗药物联合膀胱灌注来增强卡介苗治疗，但由于高剂量时的严重刺激作用和治疗不耐受，结果远不能令人满意。因此，采用“生物素-链霉亲和素策略”将阿霉素（DOX）封装在活卡介苗细菌（DOX@BCG）内的纳米颗粒来改善治疗效果。 BCG 与膀胱上皮的粘附有助于将 DOX@BCG 精确靶向局部肿瘤细胞，同时增加治疗药物的肿瘤内转运。由于 BCG 免疫疗法、DOX 化疗和 DOX 诱导的免疫原性肿瘤细胞死亡之间的协同作用，DOX@BCG 有效抑制癌症进展并延长原位膀胱癌大鼠/小鼠的生存期；此外，它表现出更好的耐受性和生物安全性，并在肿瘤微环境中建立抗肿瘤免疫力。因此，载药活卡介苗细菌递送系统在膀胱癌膀胱内治疗中具有巨大的临床转化潜力。
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