From Phenomenon to Precision: Addressing Key Challenges in Harnessing Nanomaterial-Induced Biological Responses for Cancer Therapy

The recent paradigm shift in nanomedicine—from passive drug delivery to active engagement with biological responses—holds great promise for advancing cancer therapy. However, the clinical translation of this approach faces significant challenges. In this letter, we highlight three critical areas requiring deeper investigation: (1) the dynamic interplay and potential antagonism between nanomaterial-induced biological pathways, such as reactive oxygen species (ROS) generation and protective autophagy; (2) the dual role of inflammation, which can either promote antitumor immunity or drive immunosuppression; and (3) the translational gap between preclinical models and human patients, emphasizing the impact of biological heterogeneity on therapeutic outcomes. We propose integrating systems biology, feedback-controlled mechanisms, and biomarker-driven clinical trials to overcome these challenges and realize the full potential of nanomaterial-enabled cancer therapies.