Recent advances in nanoparticles targeting TGF-β signaling for cancer treatment

Multiple therapies blocking TGF-β signaling have been investigated in preclinical and clinical trials over the past few decades; nevertheless, the outcomes of clinical trials are disappointing due to the double-faced systemic effects of TGF-β and the complexity of the tumor microenvironment. Intelligent nanodelivery systems engineered with responsive stimuli and targeting capabilities address the Janus-faced biology of TGF-β through spatially precise inhibition. Nanoparticles targeting TGF-β reciprocally create a positive feedback loop that enhances the penetration and delivery efficiency of nanoparticles because of the role of TGF-β in remodeling the tumor microenvironment. This review first outlines the function of TGF-β signaling, summarizes various tools for suppressing TGF-β signaling and provides an exhaustive emphasis on advanced nanoparticles targeting TGF-β. This review elucidates the symbiotic interplay between TGF-β blockade and nanoparticles, where nanomaterial-based strategies refine the specificity of TGF-β targeting, while the blockade of TGF-β reciprocally enhances the efficiency of nanoparticle-mediated delivery. Additionally, current challenges and future directions are highlighted to guide the future development of TGF-β blockade strategies and nanoparticles for antitumor therapy.