Biomimetic LHRH-functionalized erythrocyte-camouflaged nanogels for targeted therapy of prostate cancer.

Chemotherapy remains a cornerstone treatment for advanced prostate cancer. Nano drug delivery systems have revolutionized targeted therapy by overcoming challenges such as poor water solubility, lack of specificity, and the side effects associated with conventional drugs. However, the rapid clearance and immunogenicity of nanoparticles limit their in vivo efficacy. Erythrocyte-encapsulated nanoparticles, which leverage abundant natural cell resources and mimic biological interfaces, exhibit promising therapeutic potential but lack specificity for prostate cancer, limiting their clinical applicability. In this study, we present a biomimetic, targeted bifunctional drug delivery system based on luteinizing hormone-releasing hormone (LHRH)-decorated red blood cell membrane vesicle (RV)-camouflaged nanogels (NGs) for targeted delivery of the chemotherapeutic agent 10-hydroxycamptothecin (HCPT) in prostate cancer. Characterization of drug-loaded membrane-coated nanoparticles (LHRH-RV-NG/HCPT) using transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed a nanoparticle size of approximately 100 nm, optimal for passive tumor targeting via the enhanced permeability and retention (EPR) effect, and enhanced by LHRH-mediated active targeting. In vitro studies demonstrated that RV coating reduced premature HCPT release, enhanced drug accumulation at the tumor site, and improved cellular uptake via LHRH. Additionally, CD47 protein on the nanoparticle surface mitigated immune clearance, thereby enhancing the therapeutic efficacy. In vivo tissue distribution studies showed that LHRH-RV-NG/HCPT nanoparticles exhibited prolonged blood circulation and superior tumor accumulation compared to other nanocarriers and free drugs. Tumor inhibition experiments further confirmed the significant anti-tumor activity of LHRH-RV-NG/HCPT, with no observable toxicity to tissues or organs, indicating excellent in vivo safety. In conclusion, our dual-layer biomimetic nanocarrier loaded with chemotherapeutic agents offers a promising new approach for the treatment of prostate cancer, particularly advanced prostate cancer.