Data-Driven, Membrane-Centric Nanomedicine in Oncology: Nanodesign, Targeting, and Therapeutic Adaptation

Cellular membranes—spanning the plasma membrane, endosomal–lysosomal system, organelle interfaces, and tumor-associated extracellular vesicles—are not passive barriers, but dynamic decision-making platforms that govern recognition, uptake, trafficking, signaling, immune engagement, and ultimately therapeutic response. In oncology, many promising nanomedicines still underperform in vivo because “targeting” is often treated as a static ligand–receptor problem, while the membrane landscape is heterogeneous, plastic, and continuously remodeled by therapy, hypoxia, metabolism, and the tumor microenvironment. This Research Topic focuses on data-driven, membrane-centric nanomedicine: approaches that quantify and model membrane states and use those insights to guide nanodesign, enable robust targeting, and support therapeutic adaptation across time, lesions, and treatment stages.We welcome contributions that integrate high-content datasets (e.g., single-cell/spatial profiling, proteomics/lipidomics/glycomics, membrane trafficking readouts, CRISPR screens, imaging and biophysical measurements, patient-derived models, and clinical correlative data) with computational and statistical frameworks (including AI/ML, mechanistic modeling, digital pathology, and multi-omic integration) to identify membrane-linked determinants of nanomedicine performance and to design nanoparticles that can adapt to evolving tumor biology.In addition, we encourage studies that dissect the molecular mechanisms governing membrane–nanoparticle interactions and leverage nanotechnology as both a therapeutic and investigative tool. This includes mechanistic interrogation of receptor clustering and nanoscale organization, lipid domain remodeling, glycocalyx architecture, membrane curvature sensing, endocytic machinery engagement, endosomal escape pathways, organelle contact site dynamics, and signaling rewiring induced by nanoparticle binding or cargo release. We welcome nano-enabled approaches such as precision-engineered ligand valency and spatial patterning, membrane-active polymers and peptides, fusogenic or curvature-inducing materials, proximity-labeling and nanoscale proteomic mapping, super-resolution and single-particle tracking methods, force spectroscopy, and genetically encoded reporters to quantify trafficking, signaling, and stress responses in real time. Studies that couple such tools with perturbation strategies—CRISPR editing, chemical inhibitors, lipid remodeling, or microenvironmental modulation—to establish causal links between membrane state and therapeutic outcome are particularly encouraged.Key themes include, but are not limited to:o Membrane atlas and target discovery: mapping actionable surfaceomes, lipidomes, glycocalyces, and receptor microdomains across tumor cells, stromal/immune compartments, and metastatic niches; accounting for inter- and intratumoral heterogeneity.o Uptake and intracellular fate as design constraints: endocytosis routes, endosomal escape, trafficking to nucleus/mitochondria/ER, lysosomal sequestration, exocytosis, and how these processes shift under therapy.o Protein corona, biointeractions, and immune interfaces: corona formation in patient-relevant biofluids, complement activation, Fc/receptor biology, phagocytic checkpoints, and strategies to tune immunogenicity or immune synergy.o Mechanobiology and transport: membrane tension, stiffness, shear, tumor architecture, vascular and lymphatic features, and their effects on nanoparticle margination, penetration, and retention.o Adaptive and feedback-guided nanotherapy: responsive or “reconfigurable” nanomaterials (stimuli-, enzyme-, or environment-triggered), dosing strategies informed by longitudinal biomarkers, and closed-loop optimization from real-world or trial data.o Translation and rigor: standardized characterization, predictive in vitro–in vivo relationships, patient stratification concepts, safety/toxicity modeling, and clinically meaningful endpoints.o Molecular mechanisms of membrane–nanoparticle interactions: Receptor clustering, lipid domain remodeling, glycocalyx architecture, curvature sensing, endocytic engagement, endosomal escape, organelle contact dynamics, and signaling rewiring, with causal links to efficacy or resistance.o Nano-enabled mechanistic interrogation and control: Engineered ligand valency, membrane-active or fusogenic materials, proximity labeling, super-resolution imaging, single-particle tracking, force spectroscopy, and genetic or pharmacologic perturbations to quantify trafficking, signaling, and guide rational nanodesign.This Topic aims to accelerate nanomedicines that are predictive, personalized, and resilient to tumor adaptation, ultimately improving therapeutic index and clinical impact.***Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Matthew A Coleman, Wei He, João Paulo Longo, Adrian Bogdan Tigu Source: https://www.frontiersin.org/research-topics/78714/data-driven-membrane-centric-nanomedicine-in-oncology-nanodesign-targeting-and-therapeutic-adaptation