肿瘤干细胞,外泌体仿生纳米颗粒 z-bo 2020-11-04 394

　　Cancer stem cells (CSCs) play an important role in tumor survival, proliferation, metastasis and recurrence. Essentially, cancer stem cells maintain the vitality of tumor cell populations through self-renewal and unlimited proliferation.

　　The movement and migration ability of tumor stem cells makes tumor cell metastasis possible. Cancer stem cells can stay in a dormant state for a long time and have a variety of drug-resistant molecules, so they are not sensitive to external physical and chemical factors that kill tumor cells. Therefore, tumors often recur after a period of time after conventional tumor treatment methods have eliminated most common tumor cells.

　　In general, tumor stem cells are the main cause of tumor recurrence, metastasis and drug resistance. The development of targeted tumor stem cells is one of the most effective strategies for clinical tumor treatment.

　　Nano drugs have unique properties such as enhanced osmotic retention (EPR), modifiable, intelligent responsiveness, and co-delivery of multiple drugs. They play an important role in precise and synergistic treatment of tumors, enhancing curative effects, and reducing toxic and side effects.

　　Nanomaterials are often coupled with targeting molecules to achieve targeted delivery of anti-tumor drugs. However, different tumor stem cells express different surface markers. How to efficiently deliver drugs to different tumor stem cells and play a role is a problem that needs to be solved urgently in tumor treatment.

　　On August 23, 2019, Nature Communications, a sub-Journal of Nature, published a joint project of Professor Yang Xiangliang and Professor Gan Lu from the School of Life Sciences of Huazhong University of Science and Technology, National Nanomedicine Engineering Technology Research Center, and the topic: Tumor exosome-based nanoparticles are efficient drug carriers Research papers for chemotherapy.

　　The

　　 research team has constructed a kind of exosomal biomimetic porous silicon nanoparticles (E-PSiNPs) that are effluxed by tumor cells, which are used for targeted drug delivery of tumor stem cells and have good anti-tumor and killing tumor stem cell capabilities.

　　This study shows that exosomes-biomimetic nanoparticles have the potential to serve as drug carriers to improve anti-cancer efficacy. Moreover, because it can effectively kill tumor stem cells, it is expected to solve major problems such as tumor recurrence, metastasis and drug resistance.

　　In recent years, biomimetic nanomedicine combined with the unique functions of natural biomaterials and the versatility of artificial nanomaterials has attracted widespread attention for drug delivery.

　　Exosomes are cell vesicles that contain complex RNA and proteins. Their size is in the nanometer range (30-150 nanometers in diameter), and a variety of cells can be secreted under normal and pathological conditions. Exosomes. It is mainly derived from multivesicular bodies formed by intracellular lysosomal particles, which are released into the extracellular matrix after fusion of the outer membrane of multivesicles with the cell membrane.

　　The Nobel Prize in Physiology or Medicine in 2013 was awarded to three scientists who discovered the regulation mechanism of cell vesicle transport. Exosomes are involved in important biological processes such as immune response, apoptosis, angiogenesis, inflammation, and coagulation. They are also involved in intercellular communication. Therefore, many studies have begun to focus on the use of exosomes to deliver drugs.

　　However, the construction of exosomal biomimetic drug carriers still faces many difficulties. The main problem is that the low yield leads to low delivery efficiency.

　　In this study, the research team constructed a kind of exosomal biomimetic porous silicon nanoparticles (E-PSiNPs) that are effluxed by tumor cells for targeted drug delivery of tumor stem cells.

　　Incubating porous silicon nanoparticles with tumor cells found that tumor cells promote the efflux of porous silicon through autophagy, and the surface of the efflux porous silicon is covered with an exosome membrane structure about 20 nm thick. Compared with traditional exosomes separation methods, the yield can be increased by 34 times, and the functional proteins of exosomes are effectively retained.

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　　E-PSiNPs have good targeting of common tumor cells and tumor stem cells, and E-PSiNPs derived from one type of tumor cell loaded with the anti-tumor drug doxorubicin (DOX@E-PSiNPs) have shown to be effective against other common tumors. The cross-uptake and effective killing effect of cells and cancer stem cells solves the problem of coupling different targeting molecules to target different cancer stem cells.

　　In addition, DOX@E-PSiNPs has good tumor tissue targeting, tumor blood vessel exudation and penetration into the deep tumor. These effects are related to the expression of the adhesion molecule CD54 on the surface of E-PSiNPs.

　　Based on the above-mentioned unique behavior, DOX@E-PSiNPs has achieved a large accumulation of tumor cells and tumor stem cells in tumor tissues, and has been shown in multiple tumor models such as liver cancer subcutaneous tumor, breast cancer in situ, and melanoma lung metastasis. Good anti-tumor and killing tumor stem cell ability.

　　In general, this research provides a new idea for tumor cell-derived exosomal bionic nanomedicine for tumor treatment.