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Isolation and Expansion of Cytotoxic Cytokine-induced Killer T Cells for Cancer Treatment
Published on: January 24, 2020
KCl Nanoparticles as Potential Inducer of Immunogenic Cell Death for Cancer Immunotherapy
Zhengjie Huang1, Xiaohong Zhang1, Yang Luo2
1School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. China.
Abstract:
Immunogenic cell death (ICD) is a promising cancer immunotherapy by inducing antigen-presenting cell maturation. Many inorganic nanomodulators have been developed for cancer therapy via ion overload, and their ICD-inducing properties have also been explored for immunotherapy. Here, we report a potassium chloride nanoparticle (PCNP)-loaded poly(lactic-co-glycolic acid) nanoparticle coated with cancer cell membrane (PC@P-CCM) for cancer therapy. Through cancer cell membrane (CCM)-achieved surface functionalization, the homotypic targeting behaviors of PC@P-CCM are dramatically enhanced. Once internalized by cancer cells, the PC@P-CCM could be degraded in acidic lysosomes, thus releasing K+ and Cl- ions. These ions can change the osmotic pressure of cancer cells, causing a hypertonic state in the cancer cells in a short time and leading to the rupture and death of cancer cells. Furthermore, these ions can stimulate cancer cells to secrete adenosine triphosphate (ATP) and high mobility group box 1 (HMGB-1); meanwhile, calreticulin (CRT) showed increased presentation on the surface of cancer cells, which can further induce dendritic cell maturation and promote the immunotherapy. This work provides a new perspective on KCl nanoparticle-based cancer immunotherapy.
Insights
We developed potassium chloride nanoparticles coated with cancer cell membranes for targeted cancer therapy. This approach induces cancer cell death and promotes an immune response for enhanced immunotherapy.
Area of Science:
- Nanotechnology
- Immunotherapy
- Oncology
Background:
- Immunogenic cell death (ICD) is a key mechanism in cancer immunotherapy.
- Inorganic nanoparticles are explored for cancer therapy via ion overload.
- Cancer cell membrane coating enhances nanoparticle targeting.
Purpose of the Study:
- To develop a novel nanoparticle for cancer therapy and immunotherapy.
- To investigate the efficacy of potassium chloride nanoparticles (PCNPs) coated with cancer cell membranes (PC@P-CCM).
Main Methods:
- Fabrication of PCNP-loaded PLGA nanoparticles coated with cancer cell membranes (PC@P-CCM).
- Evaluation of homotypic targeting and cellular uptake.
- Assessment of ion release, osmotic pressure changes, and cell death induction.
- Analysis of ICD marker secretion (ATP, HMGB-1) and presentation (CRT).
Main Results:
- PC@P-CCM demonstrated enhanced homotypic targeting and internalization by cancer cells.
- Degradation in lysosomes released K+ and Cl- ions, causing hypertonic stress and cancer cell death.
- Cancer cells released ATP and HMGB-1, and presented CRT, indicating ICD.
- The treatment promoted dendritic cell maturation, enhancing immunotherapy.
Conclusions:
- PC@P-CCM is an effective nanomodulator for cancer therapy via osmotic lysis and ICD induction.
- This nanoparticle system offers a new strategy for cancer immunotherapy.
- The study highlights the potential of KCl nanoparticles in cancer treatment.
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