Photothermal therapy is to use materials with high photothermal conversion efficiency, inject them into the human body, make them gather in tumor tissue, and convert light energy into heat energy under the irradiation of an external light source (generally near-infrared light). kill cancer cells.
It has the characteristics of high selectivity, small systemic side effects, short treatment time (about a few minutes), and obvious treatment effect.
In recent years, the precise treatment of tumors has become the trend of clinical treatment of tumors.
With the continuous efforts of researchers, photothermal therapy, a nanomedicine-based tumor treatment method, has gradually entered people's field of vision.
The team of Cai Lintao, a researcher at the Institute of Biomedicine and Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, and the team of Tang Benzhong, a professor at the Hong Kong University of Science and Technology and the Chinese University of Hong Kong (Shenzhen), have developed a new AIE nano-gas drug delivery system. The unique strategy of heat shock proteins provides a new idea for low-temperature photothermal therapy of tumors.
The relevant research results were recently published online in the international journal "German Applied Chemistry".
Exploring new strategies for low-temperature photothermal therapy
In addition to the traditional "three axes" of surgery, chemotherapy, and radiotherapy for treating tumors, today's targeted drugs, interventional therapy, and immunotherapy for tumors also provide doctors with more choices.
"Photothermal therapy is also a new non-invasive and highly targeted cancer treatment method that has emerged in recent years." Wang Sheng, a professor at the School of Life Sciences of Tianjin University, introduced that this therapy uses materials with high photothermal conversion efficiency , inject it into the human body, make it accumulate in the tumor tissue, and convert the light energy into heat energy under the irradiation of an external light source (usually near-infrared light) to kill cancer cells.
Since local treatment can be achieved by controlling the light irradiation position and irradiation time, photothermal therapy has high selectivity, less systemic side effects, and short treatment time (about a few minutes), and the treatment effect is obvious.
"However, the strong laser will increase the local temperature. If the tissue temperature is higher than 60 °C, protein denaturation and cell membrane damage will cause instantaneous cell death. Photothermal therapy can kill the tumor while 'injuring the innocent', burning the normal near the tumor. However, lowering the treatment temperature will affect the treatment effect.” Wang Sheng said that how to perform photothermal therapy at lower temperatures, especially below 42 °C, is of great value for the future clinical transformation of cancer phototherapy.
It is not impossible to solve this problem.
Scientists have discovered that when an organism is exposed to high temperatures, the heat stimulates the synthesis of a protein that protects the organism itself.
Such heat stress proteins are called heat shock proteins.
This protein is found in everything from bacteria to mammals.
"In the process of photothermal therapy, if the synthesis of heat shock proteins is inhibited, the heat resistance of tumor cells can be reduced, so as to achieve the purpose of killing tumor cells without damaging normal tissue cells at a relatively low temperature. Heat treatment has achieved good results." Wang Sheng explained.
Inhibition of heat shock protein synthesis is usually achieved by chemical small molecule inhibitors (such as gambogic acid, 17-AAG, JG-98, etc.) or siRNA.
However, most chemical small-molecule inhibitors are often poorly water-soluble and highly toxic, while siRNAs are often inefficient in delivery and are inherently unstable, which greatly limits the application of these methods in low-temperature photothermal therapy.
Researchers have been looking for more effective heat shock protein inhibition strategies to improve the efficacy of low-temperature photothermal therapy for tumors.
Adding gas therapy to photothermal therapy
This time, Cai Lintao's team and Tang Benzhong's team developed a new type of AIE nano-gas drug delivery system, and for the first time proposed a unique strategy for inhibiting heat shock proteins based on carbon monoxide gas.
"At present, gas therapy is also an emerging therapeutic strategy in tumor treatment. Gases such as carbon monoxide, nitric oxide, hydrogen sulfide and sulfur dioxide are used to play an important regulatory role in various physiological processes of cells, tissues or organisms." Wang Sheng According to reports, this study is the first to use gas to regulate heat shock proteins to enhance the effect of low-temperature photothermal therapy on tumors.
According to reports, the study constructed a tumor microenvironment-triggered AIE nano-gas drug delivery system, which is also called "AIE nano-bomb".
When the "AIE nanobomb" encounters hydrogen peroxide overexpressed in the tumor microenvironment, it rapidly releases carbon monoxide gas.
Wang Sheng introduced that "AIE nanobomb" is a nano-hybrid aggregate formed by co-assembly of AIE polymer photothermal material and mPEG(CO), a novel amphiphilic therapeutic gas carrier material synthesized by carbonyl iron. .
Under the excitation of laser, this aggregate can emit strong near-infrared fluorescence and has a photothermal conversion efficiency as high as 38.1%.
Hydrogen peroxide triggers an "explosion" of the nanohybrid aggregates, releasing large amounts of carbon monoxide gas in a short time on a local scale.
The research results show that the carbon monoxide released during photothermal therapy using "AIE nanobombs" can effectively inhibit the overexpression of heat shock proteins and improve the effect of low-temperature photothermal therapy on tumors.
At the same time, carbon monoxide can also inhibit the rapid proliferation of tumor cells to a certain extent.
"In addition to the new breakthroughs in low-temperature photothermal therapy strategies this time, researchers are also actively trying in terms of photothermal conversion reagents and combination strategies." Wang Sheng gave an example. For example, researchers are currently improving organic photothermal conversion. Considerable progress has been made in the potential of reagents, including increased tumor targeting.
In addition, the development of organic photothermal conversion reagents has also made good progress.
Researchers have found that many organic compounds, including diketopyrrolopyrroles, theobromine, porphyrins, polymers, etc., can produce good photothermal effects.
Compared with the more widely used and studied inorganic materials for photothermal therapy, organic photothermal conversion reagents stand out due to their good biodegradability and easy renal clearance.
In addition, organic photothermal conversion reagents have advantages in reproducibility, control, preparation, and ease of synthetic modification.
"my country has a solid research foundation in the development of photothermal conversion reagent materials and is at the international leading level," said Wang Sheng.
In March 2022, "Advanced Functional Materials" published the results of Professor Wang Hongming's team at Nanchang University. The team designed and synthesized an amphiphilic squaraine (SQ) with polyethylene glycol (PEG) chains as hydrophilic anchors. ) dye PSQ.
In aqueous solution, PSQ spontaneously self-assembles into uniform nanospheres, PSQ-NSs, with strong near-infrared absorption, high quenched fluorescence, good water solubility, physiological stability, and biocompatibility. 81.2%, showing great potential as a photothermal conversion reagent for photothermal therapy.
Professor Jiang Jun's research group from the School of Chemistry and Materials Science, University of Science and Technology of China, in conjunction with Wang Yucai's research group from the Department of Life Science and Medicine, discovered a new material HMO with a metal-like electronic structure, which can achieve efficient light absorption of infrared light. , which can greatly improve the effect of photothermal therapy on the deep tissue of the tumor, while reducing side effects.
In December 2021, relevant research results will be published in Advanced Functional Materials.
Entering the clinic still needs to break through the technical difficulties
"Although researchers have achieved certain results in photothermal therapy, photothermal therapy is still in the stage of basic research and clinical research, and it has not yet been applied to the clinic on a large scale." Wang Sheng said that the main reason is that There are some technical difficulties to be overcome.
First of all, the penetration depth of the laser is limited and cannot penetrate deep into the human body, so it is only suitable for some superficial tumors, and it is somewhat helpless for tumors inside the body.
Secondly, in the choice of treatment temperature, high temperature treatment (above 50°C) is likely to cause damage to normal tissues around the tumor, while low temperature photothermal therapy (42°C-46°C) is likely to cause therapeutic effects due to the expression of heat shock proteins in tumor cells. not good.
Third, in the selection of photothermal conversion reagent materials, some organic small molecules with high safety have poor photothermal stability, and the potential toxicity of nanomaterials with high stability needs further study.
"At present, photothermal therapy is mainly used in tumor treatment. In addition, some studies have shown that photothermal therapy can also be used for anti-infection, obesity treatment, and vascular disease treatment." Wang Sheng introduced.
Recently, the team of Wang Bailiang, a professor at Wenzhou Medical University, published their latest research in ACS Nano. The team developed a mild photothermal nanotherapeutic platform formulated through the self-assembly of pH-responsive phenothiazine dyes.
These organic nanoparticles with a photothermal conversion efficiency as high as 84.5% can achieve effective low-temperature photothermal bacterial inhibition under the conditions of 650 nm laser irradiation and pH 5.5 with only an ultra-low light dose.
This year, a weight loss "black technology" was also published in "ACS Nano". The scientific research team from Nanyang Technological University in Singapore and the University of Cambridge in the United Kingdom carried out a "transdermal photothermal drug therapy to reshape adipose tissue in obesity and metabolic disorders". "Research.
The team developed a hydrogel containing copper sulfide nanoparticles that uses near-infrared light-converted heat to burn subcutaneous fat.