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Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, and interested parties.
Long press or scan the QR code below to follow us.
iNature chemotherapy's nano-drugs can use proximity to increase tumor penetration.
However, the effects of proximity may be limited by the consumption of chemotherapeutic agents and the resistance of internal hypoxic tumor cells.
On April 16, 2021, the Sun Jin team of Shenyang Pharmaceutical University published a research paper titled "Apoptotic body–mediated intercellular delivery for enhanced drug penetration and whole tumor destruction" online in Science Advances.
The research first proposed and proved that apoptosis is small.
ApoBDs can carry the remaining drugs to neighboring tumor cells after apoptosis.
In order to enhance the proximity effect based on ApoBD, this study prepared disulfide-bonded prodrug nanoparticles composed of camptothecin (CPT) and the prodrug PR104A activated by hypoxia.
CPT kills external normoxic tumor cells to produce ApoBD, while PR104A remains inactive, and the remaining drugs can be effectively delivered to internal tumor cells through ApoBD.
Although CPT has low toxicity to internal hypoxic tumor cells, PR104A can be activated to exert strong cytotoxicity, which further promotes the deep penetration of remaining drugs.
This synergistic approach can overcome the limitations of the proximity effect to penetrate solid tumors deeply to destroy the entire tumor.
In addition, on November 4, 2020, the Sun Jin team of Shenyang Pharmaceutical University published an online study titled "Trisulfide bond–mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity" in Science Advances.
The paper, the study reported that the simple insertion of trisulfide bonds can transform adriamycin homodimer prodrugs into self-assembled nanoparticles, with three benefits: high drug loading (67.
24%, w/w), high self-assembly Stability and high tumor selectivity.
Therefore, compared with normal cells, the trisulfide bridged prodrug nano-assembly exhibits highly selective cytotoxicity to tumor cells, thereby significantly reducing the systemic toxicity of doxorubicin.
The research findings provide new insights for the design of advanced redox-sensitive nano-DDS for cancer treatment (click to read).
On July 19, 2019, the Sun Jin team of Wuya College of Shenyang Pharmaceutical University published an article titled "Probing the impact of sulfur/selenium/carbonlinkages on prodrug nanoassemblies for cancer therapy" on Nature Communications, using sulfide bonds, two Sulfur bond, selenoether bond and carbon chain containing diselenide bond are used as the connection.
Combining paclitaxel (PTX) and citronellol (CIT) shows that four redox-responsive prodrugs can self-assemble into uniform size NPs.
High drug load (click to read).
It has been found that chemotherapy nano-drugs can enhance the penetration of drugs in solid tumors and expand their therapeutic effects through proximity effects.
The proximity effect means that tumor cells may become in-situ drug depots after absorbing drug-loaded nanoparticles (NPs).
When the drug-loaded NP induces cell apoptosis, the remaining drug will be released from the dead or dying cells and then infect surrounding cells.
The detailed mechanism of drug transport from reservoir cells to other cells needs to be further clarified.
However, after tumor cell death, there may be other ways to efficiently transport large amounts of NP within the cell.
When tumor cells undergo apoptosis, the cell membrane shrinks, divides and wraps the cytoplasm, thereby producing apoptotic bodies (ApoBDs).
Therefore, the remaining medicine can be stored in ApoBD.
The elimination of apoptotic cells is mainly achieved by "professional phagocytes" or "non-professional neighboring cells" such as macrophages.
Professional phagocytes are usually not abundant at the site where apoptosis occurs.
Therefore, non-professional neighboring cells usually clear apoptotic cells during development.
In addition, considering the nutritional deficiency of tumor cells, they usually absorb nutrients through macropinocytosis, and at the same time clear macromolecules in the microenvironment, such as ApoBDs.
Theoretically, the proximity effect can promote the constant penetration of chemotherapeutic agents into the tumor until all tumor cells are killed.
The limitation of penetration may be attributed to the consumption of chemotherapeutic agents and the resistance of internal hypoxic tumor cells.
Hypoxia-activated prodrugs (HAPs) are a class of drugs that remain non-toxic under normoxia, but can be converted into toxic drugs by reductases that are highly expressed in hypoxic tumor areas.
Therefore, combining chemotherapeutics with HAP can provide a synergistic approach to overcome the proximity effect of deep tumor penetration and the limitations of the overall tumor killing effect.
The prodrug nano-assembly is a new type of self-released nano-platform through drug conjugates.
It has many advantages, such as simple manufacturing, high drug loading, prolonged blood circulation, and reduced carrier-related toxicity.
In addition, due to the significantly different redox levels between tumor cells and normal cells, redox reactive nano-drug delivery systems have attracted widespread attention.
Therefore, self-assembled prodrug nanoparticles with redox-sensitive drug release behavior have great potential in combination therapy.
Here, the study prepared CSSP NP by self-assembly of the heterodimeric prodrug CPT-SS-PR104A composed of camptothecin (CPT), HAP PR104A and disulfide bonds.
Unsurprisingly, high levels of cytoplasmic glutathione (GSH) may trigger the cleavage of disulfide bonds, thereby rapidly releasing CPT and PR104A.
CPT killed the external normoxic tumor cells, resulting in ApoBD co-loaded by CPT and PR104A.
ApoBD can be swallowed by neighboring cells, thereby delivering the drug to the internal hypoxic tumor cells.
The drug content of CPT is gradually consumed by normoxic cells, hypoxic cells are also resistant to CPT, and low-consumption PR104A can be activated to exert cytotoxicity in hypoxic cells, thereby further penetrating the drug.
The study shows that the proximity effect mediated by ApoBD can promote CSSP NPs to achieve enhanced tumor penetration, thereby eliminating all tumor cell subpopulations.
Reference message: https://advances.
sciencemag.
org/content/7/16/eabg0880
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, and interested parties.
Long press or scan the QR code below to follow us.
iNature chemotherapy's nano-drugs can use proximity to increase tumor penetration.
However, the effects of proximity may be limited by the consumption of chemotherapeutic agents and the resistance of internal hypoxic tumor cells.
On April 16, 2021, the Sun Jin team of Shenyang Pharmaceutical University published a research paper titled "Apoptotic body–mediated intercellular delivery for enhanced drug penetration and whole tumor destruction" online in Science Advances.
The research first proposed and proved that apoptosis is small.
ApoBDs can carry the remaining drugs to neighboring tumor cells after apoptosis.
In order to enhance the proximity effect based on ApoBD, this study prepared disulfide-bonded prodrug nanoparticles composed of camptothecin (CPT) and the prodrug PR104A activated by hypoxia.
CPT kills external normoxic tumor cells to produce ApoBD, while PR104A remains inactive, and the remaining drugs can be effectively delivered to internal tumor cells through ApoBD.
Although CPT has low toxicity to internal hypoxic tumor cells, PR104A can be activated to exert strong cytotoxicity, which further promotes the deep penetration of remaining drugs.
This synergistic approach can overcome the limitations of the proximity effect to penetrate solid tumors deeply to destroy the entire tumor.
In addition, on November 4, 2020, the Sun Jin team of Shenyang Pharmaceutical University published an online study titled "Trisulfide bond–mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity" in Science Advances.
The paper, the study reported that the simple insertion of trisulfide bonds can transform adriamycin homodimer prodrugs into self-assembled nanoparticles, with three benefits: high drug loading (67.
24%, w/w), high self-assembly Stability and high tumor selectivity.
Therefore, compared with normal cells, the trisulfide bridged prodrug nano-assembly exhibits highly selective cytotoxicity to tumor cells, thereby significantly reducing the systemic toxicity of doxorubicin.
The research findings provide new insights for the design of advanced redox-sensitive nano-DDS for cancer treatment (click to read).
On July 19, 2019, the Sun Jin team of Wuya College of Shenyang Pharmaceutical University published an article titled "Probing the impact of sulfur/selenium/carbonlinkages on prodrug nanoassemblies for cancer therapy" on Nature Communications, using sulfide bonds, two Sulfur bond, selenoether bond and carbon chain containing diselenide bond are used as the connection.
Combining paclitaxel (PTX) and citronellol (CIT) shows that four redox-responsive prodrugs can self-assemble into uniform size NPs.
High drug load (click to read).
It has been found that chemotherapy nano-drugs can enhance the penetration of drugs in solid tumors and expand their therapeutic effects through proximity effects.
The proximity effect means that tumor cells may become in-situ drug depots after absorbing drug-loaded nanoparticles (NPs).
When the drug-loaded NP induces cell apoptosis, the remaining drug will be released from the dead or dying cells and then infect surrounding cells.
The detailed mechanism of drug transport from reservoir cells to other cells needs to be further clarified.
However, after tumor cell death, there may be other ways to efficiently transport large amounts of NP within the cell.
When tumor cells undergo apoptosis, the cell membrane shrinks, divides and wraps the cytoplasm, thereby producing apoptotic bodies (ApoBDs).
Therefore, the remaining medicine can be stored in ApoBD.
The elimination of apoptotic cells is mainly achieved by "professional phagocytes" or "non-professional neighboring cells" such as macrophages.
Professional phagocytes are usually not abundant at the site where apoptosis occurs.
Therefore, non-professional neighboring cells usually clear apoptotic cells during development.
In addition, considering the nutritional deficiency of tumor cells, they usually absorb nutrients through macropinocytosis, and at the same time clear macromolecules in the microenvironment, such as ApoBDs.
Theoretically, the proximity effect can promote the constant penetration of chemotherapeutic agents into the tumor until all tumor cells are killed.
The limitation of penetration may be attributed to the consumption of chemotherapeutic agents and the resistance of internal hypoxic tumor cells.
Hypoxia-activated prodrugs (HAPs) are a class of drugs that remain non-toxic under normoxia, but can be converted into toxic drugs by reductases that are highly expressed in hypoxic tumor areas.
Therefore, combining chemotherapeutics with HAP can provide a synergistic approach to overcome the proximity effect of deep tumor penetration and the limitations of the overall tumor killing effect.
The prodrug nano-assembly is a new type of self-released nano-platform through drug conjugates.
It has many advantages, such as simple manufacturing, high drug loading, prolonged blood circulation, and reduced carrier-related toxicity.
In addition, due to the significantly different redox levels between tumor cells and normal cells, redox reactive nano-drug delivery systems have attracted widespread attention.
Therefore, self-assembled prodrug nanoparticles with redox-sensitive drug release behavior have great potential in combination therapy.
Here, the study prepared CSSP NP by self-assembly of the heterodimeric prodrug CPT-SS-PR104A composed of camptothecin (CPT), HAP PR104A and disulfide bonds.
Unsurprisingly, high levels of cytoplasmic glutathione (GSH) may trigger the cleavage of disulfide bonds, thereby rapidly releasing CPT and PR104A.
CPT killed the external normoxic tumor cells, resulting in ApoBD co-loaded by CPT and PR104A.
ApoBD can be swallowed by neighboring cells, thereby delivering the drug to the internal hypoxic tumor cells.
The drug content of CPT is gradually consumed by normoxic cells, hypoxic cells are also resistant to CPT, and low-consumption PR104A can be activated to exert cytotoxicity in hypoxic cells, thereby further penetrating the drug.
The study shows that the proximity effect mediated by ApoBD can promote CSSP NPs to achieve enhanced tumor penetration, thereby eliminating all tumor cell subpopulations.
Reference message: https://advances.
sciencemag.
org/content/7/16/eabg0880
