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iNature's traditional anti-cancer strategies (such as chemotherapy and radiotherapy) are accompanied by long-standing problems of efficacy and adverse side effects, and there is an urgent need to explore and develop new high-performance methods.
Recently, photothermal therapy (PTT) has received more and more attention due to its minimal invasiveness, spatiotemporal accuracy, reproducible activity, negligence of drug resistance, and specific advantages of phototoxicity limited to the target area.
.
On March 26, 2021, Ma Guanghui, Wei Wei and Tian Zhiyuan from the University of Chinese Academy of Sciences published a joint communication titled "Near-infrared light-triggered platelet arsenal for combined photothermal-immunotherapy against cancer" in Science Advances.
Research paper, the research developed a bionic preparation based on anti-cancer platelets (N + R @ PLTs), which integrates photothermal nanoparticles (N) and immunostimulants (R) into platelets (PLTs).
Utilizing the aggregation properties of platelets and high light and heat capacity, N + R @ PLT targets defective tumor vascular endothelial cells and accumulates at the site of acute vascular injury caused by local high temperature generated by N in the positive feedback aggregation cascade.
It plays the role of arsenal and then secretes nano-scale platelets (nPLT) to transport the active ingredients to deep tumor tissues.
Immunostimulants enhance the immunogenicity of antigens released from ablative tumors, thereby inducing a stronger immune response to residual, metastatic and recurrent tumors.
After being activated by low-power near-infrared light radiation, the photothermal and immunological components have synergistically played a very high therapeutic effect in nine mouse models that mimic a series of clinical requirements.
Taken together, these results show the great promise of using the biomimetic PLT platform in high-performance and anti-cancer combination therapies.
Traditional anti-cancer strategies (such as chemotherapy and radiotherapy) are accompanied by long-standing problems of efficacy and adverse side effects, and there is an urgent need to explore and develop new high-performance methods.
Recently, photothermal therapy (PTT) has received more and more attention due to its minimal invasiveness, spatiotemporal accuracy, reproducible activity, negligence of drug resistance, and specific advantages of phototoxicity limited to the target area.
.
Taking into account the lower biological toxicity and higher tissue penetration depth, near infrared light (NIR) is always used for PTT treatment.
Photosensitizers (such as indocyanine green, gold nanorods and copper sulfide) can convert light energy into heat through vibration relaxation, surface plasmon resonance or lattice structure, and can effectively generate high heat at the tumor site to kill the tumor cell.
In order to improve the accumulation of photosensitizers at tumor sites, many types of nano-scale carriers have been developed to take advantage of the enhanced permeability and retention of random leakage caused by abnormal openings and defects of tumor blood vessels.
The further functionalization of targeting ligands enables these nanocarriers to further confer active affinity to tumor cells, thereby providing the potential to optimize anti-cancer potential.
Despite its promise, PTT based on nanocarriers still faces a series of key problems.
For example, current active targeting methods are highly dependent on the successful identification of receptors specifically expressed on tumor cells.
Unfortunately, cancer heterogeneity, especially the unstable and heterogeneous expression of these receptors during tumor development and/or between different tumors and patients, greatly impairs the efficiency of targeting.
In addition, the penetration of nanocarriers in tumors is limited by the tight extracellular matrix and the associated abnormally high interstitial pressure.
Therefore, in most cases, it is very difficult to completely ablate large tumors.
Therefore, in order to improve these methods, it is of utmost importance to develop new PTT-based drugs, which should be reliably enriched and penetrated to the tumor site, and show higher therapeutic efficacy through additive or even synergistic effects.
Recently, platelets (PLT) have been used as effective anti-cancer carriers through a variety of mechanisms, such as vascular endothelial adhesion, aggregation caused by surgical injury, and nano-scale vesicles secreted after activation.
PLT is used to achieve targeted delivery of antibodies to tumors through vascular adhesion, thereby inhibiting tumor growth.
In terms of PTT, recent studies have shown that hyperthermia can induce tumor cells to release antigens.
This response not only reveals the intrinsic link between the underlying mechanism of PTT and immune activation, but also encourages the combination of PTT and immunotherapy to improve anti-cancer treatment.
Inspired by these studies of PLT-based drug delivery and the synergistic mechanism of PTT and immunotherapy, the study reports the development of biomimetic PLT libraries for combined cancer therapy.
In this structure, the block copolymer naphthalimide-bithiophene derivative (NDI-BT) is designed as a photothermal material, and then photothermal nanoparticles (N) are synthesized and combined with the immunostimulant R837 hydrochloric acid The salt (R) is imported into the PLT together to construct an engineered PLT (N + R @ PLT).
After intravenous injection, N + R @ PLTs act as a circulatory sentinel in the blood and are sensitive to vascular damage.
Since the connection between the vascular endothelial cells near the tumor tissue is always weakened by defects, a part of N + R@PLT can act as a spearhead to trigger the adhesion of these vascular endothelial cells, thereby initially transporting the N + R cargo to the vascular endothelium cell.
After irradiation with NIR, local hyperthermia will cause acute vascular injury, which will then cause a cascade of aggregation reactions, resulting in blockages in tumor blood vessels.
In this regard, it is possible to recruit more enhanced PLTs in a way that relies more on feedback, so that further accumulation of N + R goods can be formed on-site.
Subsequently, these activated PLTs further produce nanoscale preplatelets (nPLT) from the plasma membrane.
These preplatelets transfer cargo to deep tumor tissues and expand the invasion area.
After PTT induces tumor ablation, the immunogenicity of the released tumor-associated antigens will induce the body's immune response to residual, metastatic and recurrent tumors.
With the help of immunostimulant R, this effect has been significantly improved.
This study systematically verified the above-mentioned advantages of PLTs and the synergistic effect of N and R in vivo, and proved effective therapeutic effects in 9 different mouse models.
Most notably, the study also demonstrated the efficacy of using human PLT (hPLTs) N + R @ hPLT arsenal in complex models based on humanized mice and patient-derived tumor xenografts (PDX).
Taken together, these results show the great promise of using the biomimetic PLT platform in high-performance and anti-cancer combination therapies.
Reference message: https://advances.
sciencemag.
org/content/7/13/eabd7614
Recently, photothermal therapy (PTT) has received more and more attention due to its minimal invasiveness, spatiotemporal accuracy, reproducible activity, negligence of drug resistance, and specific advantages of phototoxicity limited to the target area.
.
On March 26, 2021, Ma Guanghui, Wei Wei and Tian Zhiyuan from the University of Chinese Academy of Sciences published a joint communication titled "Near-infrared light-triggered platelet arsenal for combined photothermal-immunotherapy against cancer" in Science Advances.
Research paper, the research developed a bionic preparation based on anti-cancer platelets (N + R @ PLTs), which integrates photothermal nanoparticles (N) and immunostimulants (R) into platelets (PLTs).
Utilizing the aggregation properties of platelets and high light and heat capacity, N + R @ PLT targets defective tumor vascular endothelial cells and accumulates at the site of acute vascular injury caused by local high temperature generated by N in the positive feedback aggregation cascade.
It plays the role of arsenal and then secretes nano-scale platelets (nPLT) to transport the active ingredients to deep tumor tissues.
Immunostimulants enhance the immunogenicity of antigens released from ablative tumors, thereby inducing a stronger immune response to residual, metastatic and recurrent tumors.
After being activated by low-power near-infrared light radiation, the photothermal and immunological components have synergistically played a very high therapeutic effect in nine mouse models that mimic a series of clinical requirements.
Taken together, these results show the great promise of using the biomimetic PLT platform in high-performance and anti-cancer combination therapies.
Traditional anti-cancer strategies (such as chemotherapy and radiotherapy) are accompanied by long-standing problems of efficacy and adverse side effects, and there is an urgent need to explore and develop new high-performance methods.
Recently, photothermal therapy (PTT) has received more and more attention due to its minimal invasiveness, spatiotemporal accuracy, reproducible activity, negligence of drug resistance, and specific advantages of phototoxicity limited to the target area.
.
Taking into account the lower biological toxicity and higher tissue penetration depth, near infrared light (NIR) is always used for PTT treatment.
Photosensitizers (such as indocyanine green, gold nanorods and copper sulfide) can convert light energy into heat through vibration relaxation, surface plasmon resonance or lattice structure, and can effectively generate high heat at the tumor site to kill the tumor cell.
In order to improve the accumulation of photosensitizers at tumor sites, many types of nano-scale carriers have been developed to take advantage of the enhanced permeability and retention of random leakage caused by abnormal openings and defects of tumor blood vessels.
The further functionalization of targeting ligands enables these nanocarriers to further confer active affinity to tumor cells, thereby providing the potential to optimize anti-cancer potential.
Despite its promise, PTT based on nanocarriers still faces a series of key problems.
For example, current active targeting methods are highly dependent on the successful identification of receptors specifically expressed on tumor cells.
Unfortunately, cancer heterogeneity, especially the unstable and heterogeneous expression of these receptors during tumor development and/or between different tumors and patients, greatly impairs the efficiency of targeting.
In addition, the penetration of nanocarriers in tumors is limited by the tight extracellular matrix and the associated abnormally high interstitial pressure.
Therefore, in most cases, it is very difficult to completely ablate large tumors.
Therefore, in order to improve these methods, it is of utmost importance to develop new PTT-based drugs, which should be reliably enriched and penetrated to the tumor site, and show higher therapeutic efficacy through additive or even synergistic effects.
Recently, platelets (PLT) have been used as effective anti-cancer carriers through a variety of mechanisms, such as vascular endothelial adhesion, aggregation caused by surgical injury, and nano-scale vesicles secreted after activation.
PLT is used to achieve targeted delivery of antibodies to tumors through vascular adhesion, thereby inhibiting tumor growth.
In terms of PTT, recent studies have shown that hyperthermia can induce tumor cells to release antigens.
This response not only reveals the intrinsic link between the underlying mechanism of PTT and immune activation, but also encourages the combination of PTT and immunotherapy to improve anti-cancer treatment.
Inspired by these studies of PLT-based drug delivery and the synergistic mechanism of PTT and immunotherapy, the study reports the development of biomimetic PLT libraries for combined cancer therapy.
In this structure, the block copolymer naphthalimide-bithiophene derivative (NDI-BT) is designed as a photothermal material, and then photothermal nanoparticles (N) are synthesized and combined with the immunostimulant R837 hydrochloric acid The salt (R) is imported into the PLT together to construct an engineered PLT (N + R @ PLT).
After intravenous injection, N + R @ PLTs act as a circulatory sentinel in the blood and are sensitive to vascular damage.
Since the connection between the vascular endothelial cells near the tumor tissue is always weakened by defects, a part of N + R@PLT can act as a spearhead to trigger the adhesion of these vascular endothelial cells, thereby initially transporting the N + R cargo to the vascular endothelium cell.
After irradiation with NIR, local hyperthermia will cause acute vascular injury, which will then cause a cascade of aggregation reactions, resulting in blockages in tumor blood vessels.
In this regard, it is possible to recruit more enhanced PLTs in a way that relies more on feedback, so that further accumulation of N + R goods can be formed on-site.
Subsequently, these activated PLTs further produce nanoscale preplatelets (nPLT) from the plasma membrane.
These preplatelets transfer cargo to deep tumor tissues and expand the invasion area.
After PTT induces tumor ablation, the immunogenicity of the released tumor-associated antigens will induce the body's immune response to residual, metastatic and recurrent tumors.
With the help of immunostimulant R, this effect has been significantly improved.
This study systematically verified the above-mentioned advantages of PLTs and the synergistic effect of N and R in vivo, and proved effective therapeutic effects in 9 different mouse models.
Most notably, the study also demonstrated the efficacy of using human PLT (hPLTs) N + R @ hPLT arsenal in complex models based on humanized mice and patient-derived tumor xenografts (PDX).
Taken together, these results show the great promise of using the biomimetic PLT platform in high-performance and anti-cancer combination therapies.
Reference message: https://advances.
sciencemag.
org/content/7/13/eabd7614
