In the long battle against cancer, researchers have been pursuing an ideal treatment that can precisely destroy tumor cells without damaging healthy tissue.
A recent study by Ye Haifeng, a professor at the School of Life Sciences at East China Normal University and the Shanghai Key Laboratory of Regulatory Biology, has brought people one step closer to achieving this goal.They proposed an innovative treatment for tumors—a "bio-bomb" of cells controlled by ultrasound—to launch precise attacks on tumors.The results were published on April 11 in Cell Reports Medicine.
With the rapid development of synthetic biology technology, an intelligent microbial delivery system has emerged, bringing new hope to the precision treatment of cancer and other diseases.These smart microbes, like microdrug factories, can sense preset signal inputs and respond precisely to specific conditions such as inflammation, infection, and tumors in the human body.
It is worth mentioning that some microorganisms have a natural affinity for tumor tissue, can colonize tumor microenvironment with low oxygen, high acid and immunosuppression, and have a natural tumor inhibition effect.However, the expression of drug proteins is often continuous in existing techniques, which may not only inhibit the growth of microorganisms themselves, but may also have adverse effects on human healthy tissues.In addition, traditional drug delivery methods lack precise control and are difficult to meet the requirements of precision medicine.
In response, Ye's team proposed a solution in the latest research, using a new tactic, acoustic genetics, which uses ultrasound to control cell behavior.
As a safety tool widely used in clinical diagnosis and treatment, ultrasound has been given a new mission in this study.The researchers cleverly used the non-invasive nature of ultrasound, deep tissue penetration, and space-time specificity to develop an ultrasound-regulated gene expression system (SINGER).The system relies on a temperature-sensitive transcription suppressor, TlpA39, which responds to tiny temperature changes triggered by ultrasound to precisely initiate the expression of specific genes.
They also demonstrated a new type of customized acoustic-genetically controlled bacteria that, stimulated by ultrasound, can locally heat up to 39 degrees Celsius, precisely triggering the efficient expression of a particular gene.This means that ultrasound allows engineered bacteria to "obediently" secrete therapeutic proteins at the right time and place, enabling precise control of tumor drug expression and release.This spatiotemporally controlled regulatory mechanism ensures that therapeutic effects are directed at tumor cells while maximizing the protection of healthy cells from harm.
Engineered bacteria are delivered to the body by intratumor injection or intravenous injection, and can selectively colonize and proliferate in areas of hypoxia and necrosis of the tumor.Under the precise control of ultrasound, these "biobombs" are activated inside the tumor, and in situ expression releases therapeutic drugs, effectively inhibiting tumor growth, and even eliminating tumors completely.
In a variety of mouse tumor models, the ultrasound-regulated engineered bacteria showed significant anti-tumor effects.Through direct injection or blood delivery, the engineered bacteria can accurately locate the tumor area and release powerful anti-cancer proteins such as Azurin protein, which can induce tumor cell apoptosis, directly kill tumor cells.In addition, the researchers explored a therapeutic strategy using Azurin and the immune checkpoint inhibitor PD-L1nb, and found that the strategy not only triggered apoptosis of tumor cells, but also activated the body's immune system, achieving dual anti-cancer effects.
The development of the SINGER system not only provides new ideas for cancer treatment, but also its high modularity and compatibility make it possible to apply this technology to the treatment of a variety of diseases.In the future, this ultrasound-controlled microbial therapy may be used to treat metabolic, inflammatory, or infectious diseases, providing patients with more personalized, noninvasive treatment options.
Although current technology still faces the challenge of more accurate delivery to deep or metastatic tumors, with the improvement of research and related technologies, ultrasound-controlled engineered bacterial therapy is expected to open up a new field of precision medicine.In the near future, ultrasound-controlled cell "biobombs" are expected to be a powerful weapon in the fight against tumors, bringing a new dawn to the vast number of cancer patients.