Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering

Area of Science:

• Oncology
• Nanomedicine
• Systems Biology

Background:

• The tumor microenvironment (TME) presents significant barriers to nanoparticle delivery and therapeutic efficacy due to its heterogeneity.
• Conventional nanomedicine strategies often fail to account for interpatient and intratumoral variations, limiting their effectiveness.
• Recent advances in multi-omics technologies offer unprecedented insights into TME complexity.

Purpose of the Study:

• To review key TME barriers impacting nanomedicine delivery.
• To propose an omics-to-design framework for engineering nanoparticles tailored to TME characteristics.
• To outline translational requirements for implementing precision nanomedicine.

Main Methods:

• Summarizing TME barriers (ECM, vasculature, hypoxia, acidosis, immune microenvironment).
• Proposing a framework integrating spatial multi-omics data with nanoparticle design.
• Discussing patient stratification, diagnostics, manufacturing, and regulatory aspects.

Main Results:

• Identification of specific TME features (receptors, barriers, niches) that govern nanoparticle behavior.
• Development of an omics-driven approach to engineer nanoparticle properties like ligand selection and release strategies.
• Highlighting the need for a shift towards stratification-matched nanomedicine libraries.

Conclusions:

• An integrated strategy combining TME biology, spatial multi-omics, and engineering is crucial for next-generation nanomedicine.
• Overcoming tumor heterogeneity requires precision engineering of nanoparticles based on spatially resolved biological data.
• This approach promises enhanced therapeutic efficacy and improved patient outcomes through tailored nanomedicine interventions.