NUS DNA Barcodes Revolutionize Gold Nanoparticles for Cancer Mitochondria Targeting

A groundbreaking advancement in cancer research has emerged from the National University of Singapore (NUS), where scientists have harnessed DNA barcodes to identify gold nanoparticles that precisely target the mitochondria of cancer cells. Mitochondria, often called the powerhouses of the cell, are crucial for energy production and are hyperactive in cancer cells, making them an ideal target for disrupting tumor growth. This high-throughput method allows researchers to screen dozens of nanoparticle variants simultaneously in living organisms, dramatically accelerating the development of targeted therapies.

The innovation addresses a longstanding challenge in nanomedicine: determining which nanoparticle designs effectively reach and function within specific subcellular compartments like mitochondria. Traditional approaches test nanoparticles one at a time, which is time-consuming and resource-intensive. NUS's platform changes that by pooling barcoded particles, injecting them into tumor-bearing mice, isolating tumor mitochondria, and using next-generation sequencing (NGS) to decode which designs succeeded. This not only reveals shape-dependent performance but also paves the way for more effective photothermal therapies, where nanoparticles absorb near-infrared light to generate heat and kill cancer cells selectively.

The Science Behind Mitochondria Targeting in Cancer Therapy

Cancer cells exhibit altered mitochondrial function, relying on these organelles for the rapid ATP production needed for uncontrolled proliferation. Targeting mitochondria can induce apoptosis (programmed cell death) by overwhelming their capacity or generating reactive oxygen species. Gold nanoparticles (AuNPs) are particularly promising due to their biocompatibility, tunable optical properties, and ability to carry payloads or convert light to heat.

In NUS's study, researchers fabricated 30 AuNP variants differing in shape—spheres, rods, triangles, and stars—and size. Each was conjugated with a unique short DNA sequence (barcode) via thiol linkages, ensuring stable attachment. When pooled and administered intravenously to mice with breast tumors, the nanoparticles accumulated in tumors via the enhanced permeability and retention (EPR) effect. Post-injection, tumors were excised, mitochondria isolated using commercial kits, and barcodes amplified via PCR for NGS analysis. Relative read counts indicated enrichment: triangular AuNPs outperformed others by up to threefold in mitochondrial delivery, attributed to superior cellular uptake and endosomal escape.

Further tests confirmed triangular AuNPs' efficacy in photothermal therapy. Under 808 nm laser irradiation, they heated mitochondria-localized regions to cytotoxic levels (>50°C), achieving significant tumor regression without systemic toxicity. This shape-specific insight is revolutionary, as previous in vitro studies often failed to predict in vivo performance.

Meet the NUS Team Driving This Nanomedicine Innovation

Leading the effort is Assistant Professor Andy Tay Kah Ping from the Department of Biomedical Engineering at NUS College of Design and Engineering (CDE), and Principal Investigator at the NUS Institute for Health Innovation & Technology (iHealthtech). Tay, a President's Young Professor and recipient of the 2025 Young Scientist Award, specializes in precision diagnostics and nanotherapeutics. "This platform bridges the gap between nanoparticle design and real-world tumor biology," Tay noted, emphasizing its potential to fast-track clinical candidates.

Lead author Huang Xingyue, a PhD candidate, along with Xuehao Tian and others, executed the experiments. Their interdisciplinary work combines materials science, bioengineering, and oncology, reflecting NUS's strength in collaborative research. The study was published in Advanced Materials (DOI: 10.1002/adma.202xxxxxx), underscoring Singapore's rising profile in global nanomedicine. For the full methodology, see the open-access paper.

This isn't Tay's first foray into barcoding; prior work on lipid nanoparticles laid the groundwork, but this is the first for subcellular in vivo screening of AuNPs.

Photo by Marek Studzinski on Unsplash

NUS's Pivotal Role in Singapore's Biomedical Research Landscape

NUS stands at the forefront of Singapore's biomedical sciences push, bolstered by the Research, Innovation and Enterprise 2025 (RIE2025) plan, which allocates S$25 billion to health and biotech. iHealthtech, launched in 2020, fosters translational research, while CDE's biomedical engineering program trains next-gen experts. This breakthrough exemplifies how NUS integrates engineering with medicine, contributing to Singapore's goal of being a global medtech hub.

Singapore's ecosystem includes collaborations with A*STAR, NUHS, and international partners. NUS ranks top globally in nanotechnology (QS Rankings), with over 500 researchers in related fields. Such innovations attract talent, with programs like the NUS Graduate School offering PhDs in nanomedicine.

The platform's scalability could screen thousands of designs, incorporating ligands or drugs. Tay's team plans human-relevant models and combinations with immunotherapy. Challenges remain: regulatory hurdles for AuNPs (FDA-approved for imaging but not therapy) and scaling production. Yet, with Singapore's Clinical Trials Unit and fast-track approvals, translation seems feasible.

Globally, similar efforts exist (e.g., MIT barcoding for LNPs), but NUS's focus on mitochondria and AuNP shapes is unique, potentially synergizing with ongoing photothermal trials.

Career Opportunities in Nanomedicine at Singapore Universities

This research highlights booming opportunities in Singapore's higher ed for biomedical engineers and nanoscientists. NUS seeks postdocs (S$60k-80k/year) in Tay's lab, focusing on in vivo screening. NTU's Lee Kong Chian School of Medicine offers faculty roles in cancer nanotech, backed by S$1B funding.

PhD stipends (~S$2.5k/month) include projects on AuNP functionalization. SMU and SUTD contribute interdisciplinary angles. With 10,000+ biotech jobs projected by 2030, skills in NGS, nanoparticle synthesis, and tumor models are gold (pun intended). Singapore's low taxes and research visas draw global talent.

Explore NUS's coverage for more team insights.

Photo by Andrej Sachov on Unsplash

Implications for Singapore's War on Cancer

Cancer claims 7,000 lives yearly in Singapore; nanomedicine could slash recurrence rates. Gov initiatives like National Precision Medicine (NPM) program (500k genomes sequenced) complement this. NUS's work aligns with Cancer Science Institute's focus on targeted therapies.

Stakeholders praise: Oncologists note reduced off-target effects; policymakers highlight economic ROI (biotech GDP 5%). Patients stand to benefit from less invasive treatments.

Challenges: Ensuring barcode stability in vivo, mitigating NP clearance by immune system. Solutions: PEGylation, shape optimization. Future: AI-driven design prediction.

This NUS triumph reinforces Singapore universities' leadership, inspiring students and researchers worldwide.