Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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Volume 5 Number 1 2026
REVIEWS (Open Access)
Immunomodulatory Nanovaccines with Built-In Imaging Tags for Tracking Lymph Node Delivery In Vivo
Bassam Mohammad A. Abualsoud 1*
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110991
Submitted: 11 April 2026 Revised: 01 June 2026 Accepted: 08 June 2026 Published: 10 June 2026
Abstract
Cancer nanovaccines promise durable, tumor-specific immunity, yet most candidates are still evaluated as though delivery were a solved problem. It is not. Whether an injected formulation actually reaches the tumor-draining lymph node, and what it does once there, has historically been inferred from end-point tissue harvests rather than observed directly. This review examines a convergent solution: immunomodulatory nanovaccines carrying built-in imaging tags that report, in real time and in vivo, where the vaccine goes and how the immune system responds. We first consolidate the physicochemical rules that govern lymphatic trafficking, where particle size (most efficiently 20–50 nm), surface charge, geometry, elasticity, and ligand decoration jointly determine interstitial transit, nodal retention, and uptake by antigen-presenting cells. We then survey antigen–adjuvant co-delivery architectures, from whole-tumor-cell and biomimetic-membrane platforms to carrier-free and dual TLR/STING systems, that drive dendritic-cell maturation and MHC-I cross-presentation. The core of the review compares the imaging modalities themselves, optical (NIR-I/NIR-II), nuclear (PET/SPECT), magnetic (MRI/MPI), and genetic reporters, each trading penetration against resolution. Finally, we connect tracking metrics to immunological outcomes: cytotoxic T-cell priming, tumor-microenvironment reprogramming, checkpoint synergy, and tertiary lymphoid structure neogenesis. Persistent barriers, tracer dissociation, reticuloendothelial clearance, and manufacturing reproducibility, are discussed as the gating problems for clinical translation.
Keywords: cancer nanovaccine; lymph node targeting; theranostics; in vivo imaging; dendritic cells; cross-presentation; tertiary lymphoid structures; immune checkpoint blockade
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