Targeted and Synergistic Codelivery of Chemotherapeutic and Nucleic Acid Drugs by Liposome-Coated MPDA Nanoparticles for Advanced Prostate Cancer Treatment

• Published in: ACS applied materials & interfaces Vol. 17; no. 6; pp. 8875 - 8885
• Main Authors: Dai, Liang, Ma, Wangteng, Song, Zixuan, Lu, Binwei, He, Yuchu, Zhang, Jidong, Wei, Dapeng, Wang, Baibing, Li, Guangming, Gao, Dawei, Wang, Yimin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12.02.2025
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and Medical Applications of Materials and Interfaces; cancer therapy; cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Docetaxel - chemistry; Docetaxel - pharmacology; Docetaxel - therapeutic use; Drug Delivery Systems; drug therapy; Fourier transform infrared spectroscopy; Humans; hypersensitivity; immunosuppression; Indoles - chemistry; Liposomes - chemistry; Male; Mice; nanoparticles; Nanoparticles - chemistry; neurotoxicity; nucleic acids; oligonucleotides; polyethylene glycol; Polyethylene Glycols - chemistry; Polymers - chemistry; porous media; prostatic neoplasms; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; RNA, Small Interfering - chemistry; RNA, Small Interfering - pharmacology; transmission electron microscopy; targeted drug delivery; synergy therapy; prostate cancer; mesoporous polydopamine nanoparticles; aptamer
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.4c17384

Docetaxel (DTX)-based chemotherapy is the primary therapeutic approach for advanced prostate cancer (PCa) when endocrine therapy proves ineffective. Traditional chemotherapy exhibits poor specificity and induces severe side effects, such as immunosuppression, neurotoxicity, and hypersensitivity. In this study, we aimed to develop a new targeted nanodrug delivery system to accurately identify PCa cells and deliver drugs. We prepared mesoporous polydopamine (MPDA) nanoparticles using a one-pot method. After loading DTX onto MPDA, siRNA was attached to the surface, which was coated with polyethylene glycol lipids film (PEG-Lips); together, this formed MDS@L. The aptamer A10-3.2 was coupled to the surface of PEG-Lips to obtain MDS@LA, which was characterized using different techniques, including transmission electron microscopy and Fourier transform infrared spectroscopy. MDS@LA exhibited excellent stability, acid-responsive release, and photothermal properties, enhancing its antitumor effects. Both in vitro and in vivo experiments revealed that MDS@LA precisely targeted PCa cells and effectively delivered DTX and siRNA, leading to significant inhibition of PCa cell growth and proliferation. This versatile nanoplatform offers a promising, precise, and efficient therapeutic approach for advanced PCa, addressing the limitations of conventional chemotherapy.