The Nucleate Artery: The Nucleate Artery: It’s cancer and immunotherapy month (again)! Plus, a promising new biosensor for safer surgeries.
We are The Nucleate Artery, a monthly newsletter focused on the latest Singaporean biotech research and events. Chat with us via our Slack community: @Senuri De Silva @Chua Damien @Devika Menon @Liang Jiaqi.
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High potential SG research, hot off the press
INFECTIOUS DISEASES: Smart Macrophages and Glowing Molecules: A New Way to Treat
@Senuri De Silva
TL;DR:
Sepsis is hard to treat due to rising antibiotic resistance and immune system failure after infection.
Researchers developed a glowing molecule (TPA2PyPh) that loads into macrophages’ fat droplets and kills bacteria hiding inside cells by damaging their DNA.
In mice with drug-resistant sepsis, this strategy greatly reduced bacterial levels and improved survival, showing promise as a new treatment when antibiotics fail.
Sepsis is a life-threatening condition caused by the body’s overwhelming immune response to infection, affecting over 30 million people each year. Treating sepsis has become increasingly difficult due to rising antibiotic resistance, and a weakened immune system post-infection makes matters worse. Bacterial sepsis triggers a massive immune response, causing widespread inflammation and potential organ damage throughout the body. Even when patients survive the initial inflammatory phase, many quickly enter an immunosuppressed state, where their weakened immune systems can no longer clear infections on their own, making antibiotics the primary treatment option. However, the growing rise of antibiotic-resistant bacteria severely limits their effectiveness, leaving patients vulnerable and sepsis harder to treat. To address this, scientists are exploring ways to restore immune function in sepsis patients without relying solely on antibiotics. One promising approach is adoptive cell transfer (ACT), where immune cells like T cells or macrophages are engineered and given to patients to boost immunity.
Among these, macrophages are especially promising because of their strong ability to swallow and kill bacteria, as well as their role in activating both the innate and adaptive immune responses. However, many bacteria have evolved clever ways to hide and survive inside macrophages, avoiding destruction and causing recurring infections. This is where lipid droplets (LDs) come into play. These fat storage structures inside cells can also serve as delivery hubs for therapeutic agents. Some fluorescent molecules, like BODIPY or Oil Red O, have already been used to track these droplets.
Building on this idea, researchers at NUS Department of Chemical and Biomolecular Engineering developed a special glowing molecule called TPA2PyPh, cleverly designed to target both lipid droplets and bacterial DNA. Its structure includes both a positively-charged hydrophilic end that can bind tightly to and disrupt negatively charged bacterial DNA, as well as hydrophobic units that allow it to easily cross cell membranes and accumulate in lipid-rich environments such as fat droplets. When loaded into macrophages, TPA2PyPh sits quietly until the cells encounter bacteria. The molecule is then transferred from the lipid droplets to the bacteria through the cells’ natural lipid uptake pathways, disrupting both the bacterial membrane and DNA, effectively killing the infection from within.
What makes TPA2PyPh even more powerful is its fluorescent property. When exposed to light, it emits strong glowing signals, making it highly useful for real-time tracking and treatment monitoring. This enables researchers and clinicians to visualize the molecule’s movement and confirm it reaches infected sites, offering both therapeutic and diagnostic value in fighting drug-resistant infections.
In tests on mice with multidrug-resistant sepsis, this treatment significantly reduced bacterial levels and greatly improved survival rates. This strategy offers a powerful new way by improving ACT to treat severe bacterial infections and sepsis especially in cases where antibiotics are no longer effective.
Learn about biotech advances in Sepsis,
MedTech Inflammatix collects FDA clearance for ER sepsis diagnostic test
ABIONYX Pharma is awarded €8.7 million from the French government to fight against Sepsis
Sepsis fatalities reduced as Microbio, ARM Hub combine AI with pathogen detection biotech
Cytovale gains momentum with $100M for its sepsis screening test
CANCER: Repurposing a psychiatric drug to treat liver cancer
@Chua Damien
TL;DR:
Ketanserin, a psychiatric drug that blocks the serotonin receptor 5-HT₂A, boosted anti-tumour immune cells in liver cancer, resulting in similar therapeutic efficacies as leading immunotherapies
Combinatorial therapy of ketanserin with the leading immunotherapy demonstrated even higher therapeutic effectiveness against liver cancer.
A new study by A*STAR IMCB positions the serotonin receptor 5-HT₂A as an unexpected but highly actionable switch for rousing immune attack in hepatocellular carcinoma (HCC), the most common form of liver cancer. Using a high-throughput chemical screen, the team pinpointed 5-HT₂A signalling as a brake on anti-tumour immunity and showed that blocking this receptor slowed tumour growth and boosted T-cell infiltration in mouse and patient-derived models of HCC.
In an inducible HCC mouse model, daily ketanserin (5-HT₂A-specific inhibitor) monotherapy prolonged survival as much as the frontline atezolizumab + bevacizumab strategy (anti-PD-L1 + anti-VEGFA). This enhanced survival vanished in genetically modified mouse models lacking adaptive immunity, confirming that adaptive immunity—rather than direct tumour toxicity—drives this therapeutic effect. Treated mice showed higher intratumoural CD8⁺ T-cell infiltration and elevated IFN-γ, a cytokine linked to better clinical outcomes in HCC patients. Importantly, adding ketanserin to the PD-L1 + VEGFA antibody combination therapy preserved—and in some mice improved—the spontaneous tumour regressions seen with the antibody pair alone, pointing to straightforward synergistic effects.
Because a wide range of 5-HT₂A antagonists—including several antipsychotics and next-generation psychedelic modulators—are already in clinical use, the work charts a swift translational path: drug-repurposing could plug an urgent gap for the 70 % of HCC patients who fail first-line checkpoint therapy or targeted kinase inhibitors.
From a commercial vantage, the timing looks ideal. Global liver-cancer drug sales stand at roughly US $3.7 billion and are forecast to top US $9.8 billion by 2030, expanding at nearly 18 % CAGR as clinicians pivot toward immunotherapies and combination regimens. HCC itself is projected to be a US $3 billion niche by the end of the decade, yet durable treatment responses remain rare with current treatments. Off-patent 5-HT₂A blockers such as ketanserin or risperidone offer low-cost, low-risk entry points for rapid Phase II trials, while patent-protected serotonergic agents (e.g., selective 5-HT₂A inverse agonists in psychiatric pipelines) could be licensed or co-developed for oncology. Safety data from thousands of neuro-psychiatric patients further de-risks development, trimming time-to-market compared with first-in-class biologics.
CANCER: Engineered Bacteria for Colorectal Cancer Immunotherapy
Devika Menon
TL;DR:
Clusters of immune cells formed inside tumors, also known as tertiary lymphoid structures (TLSs) are associated with better survival outcomes
Bacteria in the gut and certain type of immune cells (ILC3s) have been closely linked to improved growth of TLSs
Scientists engineered bacteria to release a cytokine called LIGHT that can promote TLS formation and maturation, thereby inhibiting tumor growth in mice
Although Colorectal Cancer (CRC) is responsible for approximately 10% of deaths globally and is the second leading cause of cancer related deaths, it remains hard to treat. While immunotherapy has not been found to be particularly effective, tertiary lymphoid structures (TLSs) - which are clusters of certain types of immune cells that can form in tumors- and especially, mature TLSs (mTLSs) have been linked to better survival rates in patients. Factors that could promote the formation of these clusters include several types of harmless bacteria present in the gut and a specific group of immune cells in the gut - ILC3s. These immune cells can regulate adaptive immunity and could be interacting with other immune cells as well as the microbiome, together playing a significant role in maturation of TLSs. However, these cells are reduced in CRC, hindering the formation and growth of TLSs.
NUS scientists hypothesized a close relationship between gut microbiota, ILC3s and TLSs, and engineered a bacteria (VNP20009 - a strain of Salmonella typhimurium) that can grow inside tumors. The bacteria, upon colonizing the tumor, releases a cytokine known as LIGHT (a signalling molecule that is a regulator of T-cell activation) - which can promote TLS formation and maturation. Upon treatment of mice models of CRC with the engineered strain of the bacteria, ILC3 levels in tumors increased. They also observed an increase in the number and size of TLSs, as well as the level of TLS maturity after treatment. Tumor growth was inhibited and tumors reduced in both size and number following treatment, resulting in mice having better survival post-treatment compared to the control mice that were treated with only bacteria or only LIGHT, indicating that the bacteria and LIGHT have a synergistic effect in promoting TLS maturation.
Tests revealed that ILC3 cells activate cancer-killing immune cells through the LIGHT-HVEM signal (a signalling pathway in T-cell activation), improving immune response to tumors. The method was found to be safe as the bacteria largely remained in the target tumors and did not cause any harmful damage to other organs. This bacterial-based immunotherapy could pave the way for a treatment of CRC that is specific and more effective.
Read more about how:
Other designer bacteria are being used for cancer immunotherapy
Gut bacteria can improve cancer immunotherapy outcomes
CANCER: Balancing Act: How Calpain Enzymes Shape Inflammation and Tumor Growth in Liver Cancer
Senuri De Silva
TL;DR:
In liver cancer, tumor-promoting inflammation driven by the cytokine IL-1α contributes to disease progression. While calpain 1 is known to activate IL-1α, the role of its close relative, calpain 2, remains unclear.
NUS researchers found that calpain 2 keeps calpain 1 and consequently IL-1α in check, inhibiting tumour progression.
The tumor microenvironment (TME) plays a key role in shaping how the immune system responds to cancer. It contains a mix of cancer cells, immune cells, fibroblasts, and other supporting cells. Some of these immune cells; like tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) can actually suppress the body’s anti-tumor response, helping the tumor grow. In advanced cancers, these cells release signals that promote blood vessel growth, dampen immune attack, and are often linked to poor survival.
The TME is also rich in cytokines, chemical messengers that either help or hinder cancer. For instance, IL-17 encourages tumor growth by attracting MDSCs, while IL-37 can slow tumor growth by reducing blood supply to the tumor. Another important cytokine, IL-1α, is known as an “alarm” signal that sparks inflammation. It exists in an inactive form (pro-IL-1α) and is activated when cut by an enzyme called calpain 1. Once active, IL-1α can worsen cancer by attracting MDSCs into the tumor.
In liver cancer models, researchers at the NUS Life Science Institute previously found that calpain 1 activates IL-1α, a molecule that promotes tumor growth. Now, they've discovered that calpain 2, a closely related enzyme, also plays an important role. When calpain 2 was removed from liver cancer cells in mice, tumors grew even faster. This was due to a rise in calpain 1 levels, which led to increased production of pro-inflammatory IL-1α.
Further experiments showed that losing calpain 2 increased levels of proteins called FoxO3 and FoxP2, which in turn boosted calpain 1 expression. This suggests that calpain 2 normally keeps calpain 1 in check, and both enzymes work together to regulate IL-1α secretion.
This newly uncovered balance between calpain 1, calpain 2, and IL-1α highlights a potential weak spot in tumors, one that could be targeted to reverse immune suppression and slow cancer growth.
Learn about recent biotech in liver cancer,
HepaRegeniX secures $23 million to push liver drug into Phase II
GSK makes $2bn bet on liver drug from US biotech
BIOSENSORS: Flexible, Reusable Biosensor Precisely Maps Arteries for Safer Surgeries
Chua Damien
TL;DR:
NUS researchers invented a flexible and reusable hydrogel biosensor to non-invasively and precisely locate critical blood vessels during surgeries, outperforming traditional methods.
This new method utilises infrared photoplethysmography (PPG) signals to map and detect damaged blood vessels.
Perforating arteries (PAs) are small but vital blood vessels connecting deeper arteries to the skin's surface, playing a key supporting role in facilitating successful surgeries like tissue transplantation, minimally invasive procedures, and targeted embolization therapy. Precise identification of PAs is crucial—especially in free-flap surgeries, where tissue harvested to repair wounds depends entirely on these vessels for survival. Current mapping methods range from handheld Doppler ultrasound to CT angiography, but each has trade-offs: expensive equipment, radiation or contrast dye exposure, and operator-dependent accuracy. To counter these, NUS researchers have developed a flexible hydrogel-based biosensor patch that noninvasively pinpoints these vessels by reading infrared photoplethysmography (PPG) signals from the skin’s surface. The thin sensor array rapidly detects the subtle pulsations of blood flow and highlights viable arteries within minutes, consistently matching gold-standard CT imaging results and eliminating the false positives that often plague Doppler probes (demonstrated in the paper, use cases 1-5).
Although traditional PPG systems struggle with skin adhesion and flexibility, the team designed an innovative hydrogel layer that conforms tightly to the skin, dramatically improving signal quality. Importantly, this hydrogel is detachable and replaceable. A brief electrical stimulus quickly weakens the gel’s attachment to the device, allowing easy removal and replacement after each patient. By combining precise PA detection, ease-of-use, portability, reduced cost, and safety (no cross-infection risks), this technology addresses critical unmet needs in reconstructive surgery. Moreover, its versatile hydrogel platform could easily adapt to other medical monitoring devices, highlighting broad clinical and commercial potential (demonstrated in the paper, use cases 6-10).
This reusable hydrogel-based biosensor technology offers substantial translational potential within the rapidly growing medical device market, particularly for surgeries requiring precise blood vessel identification. By addressing key limitations of current methods—high cost, complexity, radiation exposure, and infection risks—this flexible, wireless, and easy-to-use solution significantly lowers barriers to clinical adoption. Its adaptable design ensures wide applicability beyond flap surgeries, extending to minimally invasive procedures and vascular treatments. As global demand rises for cost-effective, patient-safe, and reusable medical technologies, the hydrogel-based biosensor is strategically positioned for rapid translation into clinical practice. This presents compelling opportunities for partnerships, licensing, and commercialization within healthcare innovation markets.
🗞️ Industry Spotlight
News from the Singapore life sciences industry
Chugai and Gero link on antibody drugs for age-related conditions.
Singapore-Korea partnership to apply AI in hair follicle regeneration research.
Switzerland’s RDP Pharma and Singapore’s A*STAR EDDC Join Forces to Develop Precision Autoimmune Therapies
WuXi XDC accelerates global expansion of bioconjugates manufacturing by revitalising Singapore site.
Gero’s ProtoBind‑Diff redefines drug discovery by designing molecules from sequence alone
Medtech player Alcon expands its manufacturing facility in Singapore.
Singapore contributes $1M to Gavi for better access to vaccines.
Danone invests in Singapore Digital Lab to expand global innovation capabilities
IHH Healthcare launches a $5M grant to boost clinical research, innovation
🎧 Nucleate Singapore Pulse
📆 Events happening this month
Conferences
Singapore Cell and Gene Therapy (SCGT) Pan Asia Summit 2025
(16-18 Jul, 8:00 AM - 6:50 PM, in person)
Frontiers in Cancer Science 2025
(5-7 Nov, TBA, abstract submission deadline 28 Jul, in person)
Networking events
Sat Health & Bio Brews Singapore
(Every Sat, 9:00 AM - 10:30 AM, in person)
BLOCK71 Founders and Funders: Meet Ventures Edition
(24 Jul, 06:00 PM - 08:00 PM, in person)
Seminars/Panel discussion
Building a Board that Drives Impact
(16 Jul, 02:30 AM - 05:30 PM, in person)
AngelCentral Masterclass Series: Implications of Deal Terms using Real World Case Studies
(16 Jul, 02:30 AM - 05:30 PM, in person)
(23 Jul, 01:00 PM - 05:00 PM, in person)
Growth Hacking and Digital Marketing for Start-ups
(24 Jul, 11:30 AM - 01:30 PM, in person)
Workshops
Developing Roadmap for Startup Success
(17 Jul Sat, 09:00 AM - 06:00 PM, in person)