image: The translation of nanomaterials from fundamental research to clinical applications in biomedicine faces multifaceted challenges, including concerns regarding biocompatibility and long-term toxicity, uncertainties in biotransformation and in vivo metabolic pathways, spatiotemporal heterogeneity within tumors, barriers to clinical translation, and insufficient precision in regulatory control. Future directions for nanomaterials in biomedical applications must not only explore novel and more intelligent strategies but also address these existing challenges. This paper presents several promising solutions to overcome these obstacles.
Credit: Li Chen
The complexity, heterogeneity, and continuous remodeling of the tumor microenvironment (TME) during tumor progression present substantial obstacles to therapeutic intervention. Nanomedicine has emerged as a promising tool to modulate the TME. Currently, more than 50 nanomedicine products worldwide have received regulatory approval for clinical use, and these nanoformulations have significantly improved therapeutic outcomes in various diseases, including malignant tumors (e.g., Abraxane, Vyxeos, Onivyde, NBTXR3), infectious diseases (e.g., Pegasys, AmBisome, Arikayce), neurological disorders (e.g., Onpattro), and other clinical indications. The team led by Professor Kai Miao from the University of Macau has systematically reviewed four primary mechanisms through which nanomaterials enhance antitumor therapy by modulating complex components within the TME.
This paper, published in the journal iMetamed, discusses the substantial impediments that the complexity and heterogeneity of the TME pose to the implementation of cancer treatment strategies, and systematically analyzes the principal factors contributing to the significant disparities in treatment efficacy and patient prognosis frequently observed between preclinical research and clinical trials of nanomaterial-based therapeutics.
According to the “2023 Global Nanotechnology R&D Investment Analysis Report” issued by the National Science Foundation, developed nations and regions, including the United States, the European Union, and Japan, invested billions of dollars in nanotechnology research and development in 2023. Although numerous fundamental studies have reported that various nanomaterials, such as iron oxide nanoparticles, gold nanorods, and mesoporous silica, exhibit promising anticancer effects in TME modulation—such as enhanced drug penetration, reversal of immunosuppression, and synergistic immunotherapy—there remains a substantial translational gap between laboratory findings and clinical applications. The current challenges and difficulties include biosafety and long‐term toxicity assessments of nanomaterials, uncertainties in in vivo biotransformation and metabolic pathways, therapeutic efficacy variations caused by the spatiotemporal heterogeneity of the TME, obstacles in translating laboratory research to clinical practice, and insufficient selectivity in the precise regulation of TME components. In the extensive literature on nanomaterial‐mediated TME modulation for anticancer therapy, researchers often overlook these issues. This has led to many nanomaterials remaining at the fundamental research stage, thus hindering further clinical application and patient benefit. Indeed, these existing problems cannot be solved by a single field or individual researchers alone; addressing them requires collaborative efforts among clinicians to pose scientific questions and collect samples, bioinformaticians to screen targets, and materials scientists to design and synthesize platforms. Overcoming these existing obstacles and challenges will enable researchers to fully exploit the advantages of nanomaterials in precisely modulating the TME, thereby improving cancer treatment outcomes. To facilitate the translation of these technologies to clinical applications, researchers must continuously optimize nanomaterials and effectively address the key challenges associated with precisely modulating the TME. This paper provides valuable insights and forward-looking perspectives that contribute significantly to efforts aimed at enhancing the efficacy, safety, and clinical applicability of nanomaterial-based therapies.