3-acetyl-11-keto-β-boswellic acid and chitosan-Ag nanoparticles for synergistic tumor-resident bacteria mediated prostate cancer therapy

Intratumoral bacteria play a critical role in prostate cancer (PCa) progression by altering the tumor microenvironment. Modulating these bacterial populations can significantly enhance the effectiveness of cancer therapies, including chemotherapy and immunotherapy. However, the use of antibiotics often yields inconsistent results due to poor targeting and the potential for bacterial resistance. In this study, we propose a novel therapeutic approach combining 3-acetyl-11-keto-<i>β</i>-boswellic acid (AKBA) with chitosan-coated silver nanoparticles (Chi-Ag NPs) to enhance PCa treatment efficacy by eliminating tumor-resident bacteria and inhibiting tumor invasion and metastasis. To address the challenge of drug targeting <i>in vivo</i>, we designed nanocomposites (SZTI01@Chi-Ag@PLGA@AKBA) that specifically target prostate-specific membrane antigen (PSMA) receptors on PCa cells. Compared to free drugs, SZTI01@APA NPs showed a 1.67-fold increase in accumulation at the tumor site. Once localized, the AKBA and Chi-Ag NP combination effectively inhibited tumor proliferation, induced apoptosis, and eliminated tumor-resident bacteria. Additionally, the nanocomposites suppressed Th17 cell infiltration and reduced IL-17 secretion, thereby inhibiting primary tumor growth and metastasis. In summary, this bacteria-targeting strategy enhances chemotherapy efficacy and immune responses, presenting a promising therapeutic approach for improving PCa treatment outcomes and advancing the development of more effective therapies.