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High-Throughput In Vivo Subcellular Analysis of Gold Nanoparticles for Tumor Mitochondrial Targeting
Xingyue Huang1, Xuehao Tian1, Kuei Chen2
1Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
Advanced Materials (Deerfield Beach, Fla.)
|February 17, 2026
Summary
A new DNA barcoding system enables high-throughput screening of mitochondrial-targeting nanoparticles for cancer therapy. Optimized nanoparticles showed high tumor accumulation and regression, paving the way for precision nanomedicine.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Mitochondrial targeting enhances cancer precision therapy.
- Gold nanoparticles (NPs) offer potential for targeted drug delivery.
- High-throughput screening methods are needed for nanomaterial optimization.
Purpose of the Study:
- To develop and validate a subcellular DNA barcoding system for high-throughput in vivo screening of mitochondrial-targeting gold nanoparticles.
- To systematically evaluate the biodistribution and targeting of diverse nanoparticle formulations.
- To identify optimal nanoparticle characteristics for effective mitochondrial delivery and cancer therapy.
Main Methods:
- Development of a DNA barcoding system for multiplexed in vivo screening of nanoparticles.
- In vitro validation of the barcode system with six PEG/TPP-modified NPs.
- Expansion of the library to 30 NP species varying in shape, size, and ligand.
- Systematic biodistribution evaluation in subcutaneous, orthotopic, and contralateral tumor models at organ, cell-subtype, and mitochondrial levels.
Main Results:
- The DNA barcoding system enabled high-throughput screening, generating over 1000 data points with reduced animal usage.
- A strong correlation was observed between tumor accumulation and mitochondrial delivery.
- 80 nm cube (CL-FA) and sphere (PL-FA) nanoparticles showed superior performance.
- CL-FA nanoparticles achieved 99% tumor regression when combined with photothermal therapy and siRNA delivery.
- Geometry-dependent protein corona formation and specific cellular uptake mechanisms were identified.
Conclusions:
- The subcellular high-throughput barcoding platform provides a rational framework for selecting inorganic nanomaterials for precision subcellular drug delivery.
- Effective tumor accumulation is a prerequisite for successful mitochondrial targeting.
- Nanoparticle geometry and surface modifications significantly influence biodistribution and therapeutic efficacy.
