Sustained delivery of celecoxib from nanoparticles embedded in hydrogel injected into the biopsy cavity to prevent biopsy-induced breast cancer metastasis

• Published in: Breast cancer research and treatment 2024-11, Vol.208 (1), p.165-177
• Main Authors: Simmons, Reese, Kameyama, Hiroyasu, Kubota, Seiko, Sun, Yunguang, Langenheim, John F., Ajeeb, Rana, Shao, Tristan S., Ricketts, Samantha, Annan, Anand C., Stratemeier, Natalie, Williams, Sophie J., Clegg, John R., Fung, Kar-Ming, Chervoneva, Inna, Rui, Hallgeir, Tanaka, Takemi
• Format: Article
• Language: English
• Subjects: Animals; Biopsy; Bone cancer; Bone marrow; Bone tumors; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Celecoxib; Celecoxib - administration & dosage; Celecoxib - pharmacology; Cell Line, Tumor; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers - chemistry; Drug Delivery Systems; Feasibility studies; Female; Glycolic acid; Humans; Hydrogels; Inflammation; Injection; Lung cancer; Macrophages; Macrophages - drug effects; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice; Nanoparticles; Nanoparticles - administration & dosage; Neoplasm Metastasis; Oncology; Oral administration; Polyesters - chemistry; Polylactic acid; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Rhodamine; Stroma; Tumor-infiltrating lymphocytes; Tumors; Wounds
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-024-07410-x

Purpose 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. Methods 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. Results 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. Conclusion 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.