Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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Volume 5 Number 1 2026
REVIEWS (Open Access)
Patient-Derived Organoid Screening of Theranostic Nanoparticles to Address Tumour Heterogeneity in Colorectal Cancer
Lamiah Hossain1*
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110972
Submitted: 04 May 2026 Revised: 23 June 2026 Accepted: 30 June 2026 Published: 02 July 2026
Abstract
Colorectal cancer remains the third most frequently diagnosed malignancy and the second leading cause of cancer death, and the reason advanced disease still resists durable control is not a shortage of drugs so much as a surplus of biological variation. Tumours differ between patients and, more awkwardly, within a single lesion, so a regimen that clears the dominant clone often leaves behind the subpopulation that later drives relapse. Theranostic nanoparticles — single vehicles that combine an imaging function with a targeted payload — were designed to sharpen delivery and let clinicians watch where a drug actually goes. Yet most of these formulations were selected in two-dimensional monolayers, which turns out to be a poor place to make that decision: flat culture overstates nanoparticle uptake by more than two-fold, builds a protein corona out of bovine rather than human proteins, and removes almost every physical barrier a nanocarrier would meet in tissue. This review argues that patient-derived organoids, and their microfluidic extensions on chip, are the missing intermediate. We synthesise evidence from organoid biobanking, nanoparticle engineering, protein-corona biology and clinical correlation studies, and we trace how organoids resolve what monolayers blur: subclone-selective uptake, lineage-specific endocytic routing, matrix-limited penetration, and the ablation of quiescent cancer stem cells. We also take seriously what organoids still cannot do — they lack perfusion, immune cells and standardised matrices — and we set out where synthetic hydrogels, immunocompetent co-cultures and AI-assisted formulation design are likely to carry the field next. The central claim is modest but consequential: screening venue is not a technical detail; it is a determinant of translational success.
Keywords: patient-derived organoids; theranostic nanoparticles; intratumoural heterogeneity; colorectal neoplasms; protein corona; organ-on-a-chip; cancer stem cells
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