Kasmita Singha
Synfinity
Published in
7 min readJul 31, 2023

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Detection of breast cancer through a microneedle and a nano-Ag/MBL film based painless and blood-free strategy.

Synbio’s Whispers: Pioneering the future of breast cancer detection.

In the vast realms of medical science, simplicity often holds the key to unleashing the greater potential to combat complex challenges. This is particularly visible in systems using synthetic biology to aid in the detection and diagnosis of breast cancer. Through the harmonious blend of refined techniques and simplified approaches, synbio has paved the way for revolutionary advancements in the early detection of this formidable disease. In this article, we embark on a journey of discovery: exploring the artistry and accessibility that synbio brings to breast cancer detection.

Mammograms have been a keystone of breast cancer detection for many years, but they have their own set of limitations. One of the major concerns is the exposure of patients to X-rays, albeit at low doses. Although the risk is generally low, the idea of undergoing repeated screenings may raise concerns, particularly for younger women who need to undergo screening for several decades. Mammography can lead to both false positive and false negative results, where an abnormality is identified but further investigation reveals it to be non-cancerous. Breast ultrasound, another detection technique, has its own limitations, primarily the reduced effectiveness in women with dense breast tissue. Breast MRI shines, yet not without restrictions. While it boasts high sensitivity, the cost incurred for this screening is a hurdle compared to low sensitivity and ineffectiveness in mammography and ultrasound. The expenses associated with equipment, maintenance, and interpretation are barriers to its widespread use. The further complications it faces are allergic reactions to the contrast dye used, disruption of any metal in the body, and failure to detect the calcium deposits in the breast that may indicate breast cancer. The sensitivity of MRI scans can result in more false positive findings. These false positive results often trigger additional tests, such as biopsies, which sow seeds of anxiety in patients. Overdiagnosis (diagnosis of a medical condition that would never have caused any symptoms or problems) is also a concern, where MRI may detect abnormalities that would cause harm. To overcome all these breast cancer detection drawbacks synthetic biology has unleashed a wealth of groundbreaking techniques.

Synthetic biology, in its essence, blends the precision of science with the ingenuity of engineering. When it comes to breast cancer detection, synbio introduces novel techniques that harness the power of genetic engineering and bioengineering to create innovative solutions. By delving into the intricacies of tissue fluids and biomarkers, researchers have paved the way for a convenient and painless approach for the detection of breast tumors in their early stages. The tissue fluid around the breast provides real-time information on cancer cells, making it more timely than blood samples. As breast cancer progresses, tumor markers change and accumulate in the tissue fluid before entering the bloodstream. Detecting these markers at an early stage in tissue fluid can lead to early diagnosis of breast cancer.

In recent years, the fascinating world of Ag nanomaterials and thin film materials has sparked excitement in biomedical and analytic fields. As the name suggests, nanocomposites are advanced materials that are created by blending polymers with inorganic solids, ranging from clays to oxides, at the nanometric scale. Their structures are more complicated than that of micro composites. It has been reported that Ag3PO4 nanocomposites have photocatalytic and antibacterial properties and have been applied in fields of bone repair and regeneration. Thin films have also been explored in tissue engineering and drug delivery for cancer treatment. Researchers have developed a novel strategy that combines microneedles with a nano-Ag/MBL film to extract and detect tumor markers directly from skin tissue fluid. This process begins by creating a small opening in the skin using microneedles, specifically targeting the surface of the mammary gland. Once the tissue fluid has exuded, a specially designed synthetic MBL membrane (Mannose Binding Lectin is a multimeric, carbohydrate-binding protein produced in the liver and secreted into the blood that plays a crucial role in the innate immune response) is applied to cover the skin. This membrane utilizes the siphon effect to collect the tissue fluid. To detect CEA (Carcinogenic Embryonic Antigen), Ag3PO4/Ag nanocomposites are employed as labels, facilitating the construction of a nano-Ag-based magnetic colorimetric sensing platform. The reaction between CEA and the Ag3PO4/Ag-TMB system results in the formation of blue products due to the oxidation of 3,3’,5,5’-tetramethylbenzidine (TMB) by Ag+. The intensity of the blue color reflects the CEA level and provides insights into the extent of tumor proliferation, allowing for a simple and colorimetric detection of Ag with a detection limit of 50nM. Higher concentrations of CEA in the tissue fluid samples result in more pronounced blue responses, aiding in identifying the approximate location of the tumor. Integrating Ag nanomaterials and thin films, a brilliant approach using microneedles and nano-Ag/MBL films for painless and blood-free tumor extraction, has opened new doors for diagnosing and detecting breast cancer.

In the world of biomedical sciences, scientists have uncovered some fascinating research on the glycan-specific nanobodies (Nbs) which present a rapid and versatile method for producing Nbs that selectively target glycans using small amounts of synthetic glycans, opening up avenues for potential application in diagnostics and therapeutics.

Glycans are carbohydrates found on cell surfaces, they play a vital role in screening the different cell types. However, their complex structures make it difficult to study them concisely. To address this challenge, scientists have developed automated glycan assembly techniques, allowing them to create uniform glycans. These glycans have paved the way for developing antibodies that specifically target glycans. Nonetheless, a common drawback of these antibodies is their lack of specificity.

Tumor-associated carbohydrate antigens (TACAs) are significant markers in cancer due to their abnormal glycosylation on cancer cells. Globo-series glycosphingolipids are a dynamic sub-family with diverse expression patterns during cell development and differentiation. Among them, Globo-H is a well-studied glycosphingolipid-TACA, originally identified in human teratocarcinoma and the in vitro model of an isolated MCF7 cell line of breast cancer cells. Globo-H is notably overexpressed in various epithelial cancers, such as breast, lung, and prostate cancer. It is associated with immunosuppression, angiogenesis(formation of new blood vessels), and the metastasis(malignant spread) of cancer cells. Recent clinical phase II/III trials using a synthetic Globo-H vaccination in breast cancer patients showed encouraging outcomes as it demonstrated a favorable effect in progression-free survival for patients who produced high enough levels of Globo-H specific antibodies.

The family of Camelidae animals, including the esteemed camels and llamas, possess a unique ability to produce conventional antibodies such as canonical Immunoglobulin(IgG) and unique antibodies known as heavy-chain-only antibodies (hcAbs). These antibodies can be engineered into nanobodies(Nbs) due to their petite size, exceptional stability, and solubility. What makes Nbs truly remarkable is their capacity to venture into dense microenvironments, such as tumor sites, with great ease.

In this groundbreaking research, scientists have crafted a method to produce nanobodies that precisely recognize glycans. They immunized an alpaca with precisely defined, synthetic glycoconjugates to raise unique hcAbs antibodies. The selected Nbs are thoroughly screened for their binding affinity to cells expressing the target glycans. Solution binding assays validate their remarkable specificity against a diverse array of synthetic glycans. Impressively, scientists have also successfully developed Nbs tailored to bind to Globo-H ,a representative TACA, marking a significant stride in biomedical research. Synbio has not only brought countless wonder achievements, but it has also demonstrated elegance through innovative biosensors, acting as tiny detectives that recognize certain biomarkers, DNA-based sensors, genetic circuits, and many more breakthroughs.

Generation of glycan-specific nanobodies

As we reach the end of our journey to this discovery, it is crucial to reflect on the remarkable progress we have witnessed, combining science and engineering to create powerful solutions. This headway promises an era of better early breast cancer detection and progress in our battle against this formidable foe. Our exploration in breast cancer detection concludes here, paving way for a voyage in breast cancer drug development, where new frontiers of hope and healing await.

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