Liu Yufei, Qi Yao, Chen Chen, Jin Yincheng, Du Shi, Qiao Jianan, Yao Jing
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
J Control Release. 2023 Oct;362:396-408. doi: 10.1016/j.jconrel.2023.08.057. Epub 2023 Sep 8.
Tumor recurrence mainly triggered by tumor residual cells significantly contributes to mortality following breast tumor resection, and meanwhile post-surgical bacterial wound infections may accelerate tumor recurrence due to a series of infection-related complications. In this study, a nano-sensor system, Van-ICG@PLT, is constructed by a membrane camouflage and small molecule drug self-assembly strategy. This nano-sensor harnesses the innate tropism of platelets (PLT) to deliver vancomycin (Van) and indocyanine green (ICG) to surgical incisions, effectively eliminating both residual tumor cells and bacterial infections. Our findings demonstrate that Van-ICG@PLT preferentially accumulates at surgical wound. Under near-infrared (NIR) laser irradiation, Van-ICG@PLT exhibits significant cytotoxicity against 4T1 cells. Additionally, it is found to significantly promote ROS production thus inhibiting Staphylococcus aureus (S. aureus) growth, underscoring the synergistic benefits of phototherapy in combination with antibiotic treatment. In the 4T1 post-surgery recurrence mice model, Van-ICG@PLT is shown to efficiently ablate tumors in tumor-bearing mice (tumor inhibition rate of about 83%), and it demonstrates an excellent anti-infective effect in mice abscess models. Taken together, Van-ICG@PLT represents a promising paradigm in post-surgical adjuvant therapy (PAT). Its dual benefit in inhibiting cancer growth and promoting antibacterial activity makes Van-ICG@PLT a valuable addition to the existing arsenal of therapeutic options available for breast cancer patients.
肿瘤残留细胞引发的肿瘤复发是乳腺肿瘤切除术后死亡率的主要原因，同时术后细菌伤口感染可能因一系列感染相关并发症而加速肿瘤复发。在本研究中，通过膜伪装和小分子药物自组装策略构建了一种纳米传感器系统Van-ICG@PLT。这种纳米传感器利用血小板（PLT）的天然趋向性将万古霉素（Van）和吲哚菁绿（ICG）输送到手术切口，有效消除残留肿瘤细胞和细菌感染。我们的研究结果表明，Van-ICG@PLT优先在手术伤口处积聚。在近红外（NIR）激光照射下，Van-ICG@PLT对4T1细胞表现出显著的细胞毒性。此外，发现它能显著促进活性氧生成，从而抑制金黄色葡萄球菌（S. aureus）生长，突出了光疗与抗生素治疗相结合的协同益处。在4T1术后复发小鼠模型中，Van-ICG@PLT显示出能有效消融荷瘤小鼠体内的肿瘤（肿瘤抑制率约为83%），并且在小鼠脓肿模型中表现出优异的抗感染效果。综上所述，Van-ICG@PLT代表了术后辅助治疗（PAT）中一种有前景的范例。其在抑制癌症生长和促进抗菌活性方面的双重益处使Van-ICG@PLT成为乳腺癌患者现有治疗选择中的一项有价值的补充。
