我们之前曾报道，浸润到小鼠乳腺肿瘤活检腔附近活检伤口的骨髓源性细胞（BMDC）中，持久的环氧合酶-2（COX-2）活性可促进巨噬细胞的 M2 转变和促转移性变化。口服 COX-2 抑制剂可抑制癌细胞的作用。因此，局部控制活检伤口中的COX-2活性可能会减轻活检引起的促转移变化。 组合递送系统-热敏可生物降解聚（乳酸）水凝胶（PLA-凝胶），包含塞来考昔封装的聚（乳酸）水凝胶-乙醇酸）纳米颗粒（Cx-NP/PLA-凝胶）-被注射到Py230小鼠乳腺肿瘤的活检腔中，以实现对伤口基质中COX-2活性的局部控制。单次活检腔内注射PLA-负载有罗丹明的纳米颗粒 (NP) 的凝胶显示，罗丹明优先持续局部递送至浸润性 BMDC，而小鼠网状内皮器官对罗丹明的吸收极少甚至不吸收。此外，与负载 PLA-gel 的相比，单次活检腔内注射 Cx-NP/PLA-gel 后观察到 M2 样巨噬细胞密度、癌细胞上皮间质转化和血管密度显着降低NP 不包含有效负载。因此，与对照组小鼠相比，活检腔内注射 Cx-NP/PLA-gel 导致肺部转移细胞明显减少。这项研究为优先向伤口中的 BMDC 持续、局部递送有效负载的可行性提供了证据。使用组合输送系统在邻近活检腔的基质中进行治疗，以减少局部炎症并有效减轻乳腺癌细胞扩散。© 2024。作者。

We have previously reported that protracted Cyclooxygenase-2 (COX-2) activity in bone marrow-derived cells (BMDCs) infiltrating into biopsy wounds adjacent to the biopsy cavity of breast tumors in mice promotes M2-shift of macrophages and pro-metastatic changes in cancer cells, effects which were suppressed by oral administration of COX-2 inhibitors. Thus, local control of COX-2 activity in the biopsy wound may mitigate biopsy-induced pro-metastatic changes.A combinatorial delivery system-thermosensitive biodegradable poly(lactic acid) hydrogel (PLA-gel) incorporating celecoxib-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Cx-NP/PLA-gel)-was injected into the biopsy cavity of Py230 murine breast tumors to achieve local control of COX-2 activity in the wound stroma.A single intra-biopsy cavity injection of PLA-gel loaded with rhodamine-encapsulated nanoparticles (NPs) showed sustained local delivery of rhodamine preferentially to infiltrating BMDCs with minimal to no rhodamine uptake by the reticuloendothelial organs in mice. Moreover, significant reductions in M2-like macrophage density, cancer cell epithelial-to-mesenchymal transition, and blood vessel density were observed in response to a single intra-biopsy cavity injection of Cx-NP/PLA-gel compared to PLA-gel loaded with NPs containing no payload. Accordingly, intra-biopsy cavity injection of Cx-NP/PLA-gel led to significantly fewer metastatic cells in the lungs than control-treated mice.This study provides evidence for the feasibility of sustained, local delivery of payload preferential to BMDCs in the wound stroma adjacent to the biopsy cavity using a combinatorial delivery system to reduce localized inflammation and effectively mitigate breast cancer cell dissemination.© 2024. The Author(s).