Sustained Delivery of Celecoxib from Nanoparticles Embedded in Hydrogel Injected into the Biopsy Cavity to Prevent Biopsy-induced Breast Cancer Metastasis

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2024 Jul 5

PMID 38969944

Authors

Reese Simmons

Hiroyasu Kameyama

Seiko Kubota

Yunguang Sun

John F Langenheim

Rana Ajeeb

Tristan S Shao

Samantha Ricketts

Anand C Annan

Natalie Stratemeier

Sophie J Williams

John R Clegg

Kar-Ming Fung

Inna Chervoneva

Hallgeir Rui

Takemi Tanaka

Affiliations

Soon will be listed here.

Abstract

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.

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