Nanomedicine Targeting Cancer-Associated Fibroblasts in Prostate Cancer: From Biological Mechanisms to Integrated Theranostic Strategies
Year: 2026
Type: article
Abstract: Fajiang Qian,1,* Jingfeng Zhou,2,* Yuan Tang,3,* Junhao Chen,4,* Jieming Zuo,4,* Keyi Gou,2 Chenxi Tan,2 Jingcheng Fang,2 Zihan Zhao,2 Junxian Zhao,5 Lingxiang Wen,6 Shi Fu,4 Jintao Yang,1 Chengjie Wang,7 Zhongsong Zhang2 1Department of Urology, Lincang People’s Hospital, Lincang, Yunnan, 677000, People’s Republic of China; 2School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, 610550, People’s Republic of China; 3School of Nursing, Chengdu Medical College, Chengdu, Sichuan, 610550, People’s Republic of China; 4Department of Urology, The Second Affiliated of Kunming Medical University, Kunming, Yunnan, 650032, People’s Republic of China; 5Department of Urology, 920th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Kunming, Yunnan, 650032, People’s Republic of China; 6School of Clinical Medicine, Kunming Medical University, Kunming, Yunnan, 650032, People’s Republic of China; 7School of Stomatology, Xinjiang Second Medical College, Karamay, Xinjiang, 834000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingfeng Zhou; Zhongsong Zhang, Email [email protected]; [email protected]: Prostate cancer (PCa) is the second most common malignancy in men worldwide. Advanced stages are characterized by tumor heterogeneity, metastasis, and resistance to androgen deprivation therapy and chemotherapy. Cancer-associated fibroblasts (CAFs), the predominant stromal cells in the PCa tumor microenvironment (TME), critically drive tumor progression, metastasis, and therapeutic resistance. Nanomedicine represents a transformative strategy for targeting CAFs. It leverages engineered nanomaterials to achieve precise drug delivery, improved bioavailability, and multimodal theranostic capabilities, which integrate diagnosis with therapy. This review comprehensively examines advances in nanomaterial-based strategies for CAF-targeted therapy in PCa. We first delineate the biology of CAFs in PCa, encompassing their origins, activation mechanisms, key markers (e.g, α-SMA and FAP), phenotypic heterogeneity, and intricate crosstalk with cancer cells, immune cells, and the extracellular matrix (ECM). We then evaluate nanomaterial-based targeting strategies and therapeutic modalities, including CAF depletion, reprogramming, and extracellular matrix remodeling, for the treatment of PCa. Subsequently, we discuss CAF-targeted nanoplatforms for theranostics, including molecular imaging probes (e.g., 68Ga-FAPI) and image-guided delivery systems that integrate precise diagnosis with therapy. Finally, we address key challenges, particularly CAF heterogeneity and nanomaterial biosafety, and outline future directions, including gene-editing integration, multi-stimuli-responsive systems, and synergistic immunotherapy combinations. Collectively, this review underscores the transformative potential of integrating CAF biology with nanotechnology to overcome therapeutic resistance in PCa and advance precision oncology.Keywords: cancer-associated fibroblasts, prostate cancer, tumor microenvironment, nanomedicine, diagnostics and therapeutics, targeted therapy
Institution: Stomatology Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7139525155
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