A novel therapeutic strategy for HER2 breast cancer by nanoparticles combined with macrophages

Abstract:In recent years, the cell membrane bionic nanoparticles as a new drug delivery system is widely used in small molecule drugs, vaccines and targeted delivery of macromolecular drugs, because of its inherited the specific receptors on the cell membrane and membrane proteins can be used to implement specific targeted delivery, and the tumor showed a good treatment effect on the disease such as model, this topic with a huge bite cell membrane of the role of tumor capture, chemical modification, make its surface specific antibody targeting tumor cells, enhance targeting, and PLGA nano ball package for the cell membrane, make its accurate reach the tumor site, under the condition of without affecting normal cells, Target therapy can be achieved. The PLGA nanoparticles wrapped by the cell membrane persist in the body for a longer time, and retain the red cell membrane surface antigen and glycoprotein, bypassing the scavenging effect of macrophages on the nanoparticles, thus building a functional nanoparticle platform. Fluorescent nanoparticles can be used to detect lesions. The experiment is based on the bionic platform of cell membrane system.

Key words: PLGA nanoparticles cell membrane Target therapy

Introduction

The biomimetic nanoparticles of cell membrane cover the biological membrane on the nano-materials to avoid the attack of the immune system. As the specific receptors or membrane proteins on the cell membrane are inherited, they can be used for specific targeted delivery. And in diseases such as tumor model shows a better therapeutic effect on commonly used medicine system, nanoparticles is PLGA drug-loading microspheres system, has good biodegradability, biocompatibility of controlled release rate of performance, but it is not stable in the physiological solution, the cell membrane bionic exists, the stability of the nanoparticles in the physiological solution escape immune cells after its with EPR effect can target tumor cells, but targeted effect is not very good, thus enhancing its targeted, tumor penetrability, it is particularly important to improve the effect of treatment and reduce the side effects.

According to statistics, 169,000 patients are diagnosed with breast cancer every year in China. HER2 positive breast cancer accounts for about 20-30%, and its insensitivity to traditional chemotherapy regimens and lack of more effective treatment are major obstacles to long-term survival of HER2 patients, while targeted HER2 drugs can increase the survival rate to about 80%.

At present, is a hotspot in the research of the pharmaceutical preparations of nanometer micro capsule of research material is mainly set in liposome technology Amphiphilic block copolymer self-assembling technology and polyelectrolyte (or biological macromolecules etc) assembled electrostatic adsorption technology Due to the formation of the nano capsule has a narrow particle size distribution, [1]particle size of easy to control, the advantages of good stability, biodegradable amphiphilic block copolymer is considered to be promising material of the micro capsule Represented by poly-lactic acid and poly-lactide polyester has good biocompatibility and biodegradability Sex, but with polyester as the raw material preparation of drug-loading nanoparticles with a hydrophobic surface, [2]make it easy to be protein adsorption and macrophages by reticuloendothelial system to identify and capture, effectively improve the hydrophilic nature of biodegradable polyester nanoparticles, prolong the cycle time of nanoparticles in the body of the amphiphilic copolymers in selective solvents self-assembly nanometer micelle, hydrophobic drugs through physical synergy into the micellar cores.[3]

Although particles and NPs has certain targeting, but this is passive targeting, active targeting, in order to improve its people has taken some measures, including immune particle and NPs, magnetic particles, etc., there are people on particles and NPs surface coated with surfactant, polyethylene glycol (peg) and other water-soluble polymer in order to change the distribution of particles in the body, or the use of lysolecithin absorption promoter or protease inhibitors such as to increase the digestive tract mucosa on drug absorption. Cancer is one of the leading causes of death in humans, and chemotherapy is still the main method in the treatment of malignant tumors.[4] How to improve the drug targeting and reduce its toxicity is the key to improve the effect of chemotherapy. Human volume experimental studies have shown that particles, especially NPs, have a strong adsorption capacity on the surface of tumor cells, which can enhance the granular activity of tumor cells, thus improving the targeting of drugs, significantly reducing the toxic and side effects of drugs, and increasing the therapeutic index. NPs research of encapsulated anticancer drugs is very active at home and abroad. Biodegradable polyester represented by poly-caprolactone, polylactic-acid, poly-hydroxyacetic acid or its block copolymer has excellent biocompatibility and is widely used in the field of biomedicine.[5]

Fig.1 shows the targeted delivery of the drug to the erythrocyte membrane.

Materials and methods

Our research idea is generated using the click chemistry on the membrane surface azide, [6]realize the huge bite cell membrane modification and coupling targeted delivery of antibody[7], enhance the immune therapy at present preliminary research achievements mainly based on the preparation of nano-materials and mouse tumor model.

Results

After a lot of contrast experiments, we finally prepared by drying method in liquid out of the average particle size of around 90 nm PLGA microspheres Early has put the cultivation of the breast cancer cell line 4 t1 were good, the cell in mice with breast cancer with people close to homology, so can reflect better treatment effect, and then we plan to package nir fluorescent dyes in nanometer microspheres ICG, the next step is the extraction of the cell membrane, azide contrast experiment was carried out.

Fig.2 shows the size of PLGA, we can see the average particle size of around 90 nm. Microspheres smaller than 100 nanometers can target parenchymal organs such as bone marrow or kidneys, and the smaller the particle size, the more penetrating the tumor cells.

Discussion and Conclusion

We constructed a bionic nanometer platform to provide experimental basis and research ideas for targeted therapy of tumors.

Acknowledgements

This work was supported by my tutor Dr.Ning and Dr.Wang. I also appreciate guidance and support from Dr.Karen. And Sincere gratitude is expressed to all the people who offered me help.

Reference

  1. Xing Guo, Lin Wang, Kayla Duval(2017)Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-Traceable Drug Release. Advanced materials.1705436.1-10.
  2. Van Vlerken LE, Amiji MM. Multi-functional polymeric nanoparticles for tumour-targeted drug delivery[J]. Expert Opin Drug Deliv, 2006, 3(2): 205-216.
  3. Becker, A. L.; Johnston, A. P. R.; Caruso, F. Layer-by-Layer-Assembled Capsules and Films for Therapeutic Delivery.Small 2010, 6, 1836–1852.
  4. Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 2002;6:319–27.
  5. Yoon H J, Kozminsky M, Nagrath S. Emerging role of nanomaterials in circulating tumor cell isolation and analysis[J]. ACS Nano, 2014, 8: 1995-2017.
  6. Xiong K, Wei W, Jin Y J, Wang S M, Zhao D X, Wang S, Gao X Y, Qiao C M, Yue H,
  7. Ma G H and Hai-yang Xie * . Biomimetic immuno-magnetosomes for high-performance
  8. enrichment of circulating tumor cells.
  9. Kuo Y C, Wang Q, Ruengruglikit C, et al. Antibody-Conjugated CdTe quantum dots
  10. for Escherichia coli detection[J]. J. Phys. Chem. C., 2008, 112:4818-4824.
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