Abstract：
Local recurrence post-surgery in early-stage triple-negative breast cancer is a major challenge. To control the regrowth of a residual tumor, we have developed an autologous therapeutic hybrid fibrin glue for intra-operative implantation. Using autologous serum proteins as stabilizers, we have optimized high drug-loaded lapatinib-NanoSera (Lap-NS; ∼66% L.C.) and imiquimod-MicroSera (IMQ-MS; ∼92% L.C). Additionally, plasmonic nanosera (PNS) with an ∼67% photothermal conversion efficiency under 980 nm laser irradiation was also developed. While localized monotherapy with either Lap-NS or PNS reduced the tumor regrowth rate, their combination with IMQ-MS amplified the effect of immunogenic cell death with a high level of tumor infiltration by immune cells at the surgical site. The localized combination immunotherapy with a Nano-MicroSera based hybrid fibrin implant showed superior tumor inhibition and survival with significant promise for clinical translation.
摘要：
早期三阴性乳腺癌术后局部复发是一项重大挑战。为了控制残留肿瘤的再生长，我们开发了一种用于术中植入的自体治疗混合纤维蛋白胶。使用自体血清蛋白作为稳定剂，我们优化了高载药量拉帕替尼-纳米血清(Lap-NS;~66%L.C.)和咪喹莫特-微血清(IMQ-MS;~92%L.C.)。此外,还开发了在980nm激光照射下具有67%光热转换效率的等离子体纳米血清（PNS）。虽然Lap-NS或PNS的局部单一疗法降低了肿瘤的再生长速率，它们与IMQ-MS的组合放大了免疫原性细胞死亡的影响,并在手术部位通过免疫细胞进行高水平的肿瘤浸润。具有基于Nano-MicroSera的杂合纤维蛋白植入物的局部组合免疫疗法显示出优异的肿瘤抑制和存活,具有用于临床转化的显著希望。
