Electroacupuncture in Combination with Bevacizumab Hydrogel Provides a Therapeutic Strategy for Bladder Cancer.

Acupuncture, a promising treatment for various diseases and a crucial component of traditional Chinese medicine (TCM), shows potential in enhancing immune function and prognosis in patients with cancer. However, its mechanisms of action in solid tumors remain unclear. This study evaluated the antitumor efficacy of electroacupuncture (EA) in bladder cancer (BC), using doxorubicin (DOX) as a reference treatment. Both DOX and EA significantly inhibited tumor growth and prolonged survival in a BC mouse model. To further investigate the underlying mechanisms, RNA sequencing (RNA-seq) and network pharmacology analyses were conducted to explore the organ-protective and neuromodulatory effects of EA. Single-cell RNA sequencing (scRNA-seq) was performed to assess the impact of DOX and EA on the heterogeneity of the tumor immune microenvironment (TIME). EA treatment led to an increased proportion of immune cells, particularly T cells and myeloid cells. Additionally, EA activated CD8+ T cells, suppressed fibroblast-mediated tumor angiogenesis, and reduced pro-inflammatory cytokine expression, contributing to organ protection and highlighting its potential for combination therapy with antiangiogenic agents. Based on these findings, bevacizumab (BEV), an antiangiogenic drug, was selected and a hyaluronic acid (HA)@sodium alginate (SA)-BEV hydrogel was developed as a drug delivery system for combination therapy with EA. HA@SA-BEV exhibited stable release in the acidic tumor microenvironment, prolonging local drug retention at the tumor site. EA combined with HA@SA-BEV effectively suppressed BC progression, enhancing antitumor efficacy. These findings provide insights into the integration of EA with anticancer agents and support its potential clinical value in cancer treatment.