Poison in the package
Nanoparticles and radiation therapy provided long-term survival of 67% of mice with brain tumors
Anastasia Gorshkova, PCR.news
Glioblastoma multiforme (MGB) is a primary brain tumor with an extremely unfavorable prognosis: only 5% of patients survive for five years after diagnosis. The main problems of drug therapy are tumor heterogeneity, high infiltration by immunosuppressive myeloid cells and the inability of many drugs to overcome the blood—brain barrier. It is known that the CXCL12/CXCR4 signaling pathway is involved in tumor development, and CXCR4 receptor antagonists (for example, AMD3100) have a potential antitumor effect, but due to toxicity and poor pharmacokinetics, they cannot be used in clinical practice.
The authors of the new article obtained synthetic protein nanoparticles (SPNP) from human serum albumin and polyethylene glycol coated with the iRGD peptide penetrating into the cell. They loaded AMD3100 drug into these nanoparticles. The researchers showed that the resulting AMD3100 SPNP nanoparticles effectively block the transmission of CXCR4 signals in three models: in mouse and human glioblastoma cells in vitro, as well as in a mouse model in vivo.
Blocking of the CXCL12/CXCR4 signaling pathway by nanoparticles reduces the permeability of the blood-brain barrier and reduces infiltration by immunosuppressive myeloid cells. Further, the authors suggested that in combination with radiation therapy, nanoparticles will cause the death of tumor cells along the path of immunogenic cell death. The analysis of the expression of specific factors showed that both in the culture of mouse and in the culture of human glioblastoma, cell death occurs precisely by this mechanism.
Combined therapy with nanoparticles and radiation therapy inhibited the progression of glioblastoma and contributed to the long-term survival of 67% of experimental mice. This was accompanied by the acquisition of a stable immunological memory and prevented the recurrence of the tumor: when the tumor cells were re-inserted into the collateral hemisphere, no signs of the disease were observed in the recovered mice. The mice showed no signs of necrosis or bleeding, as well as a violation of the architecture of the brain. Due to the pinpoint effect, low toxicity and steady reprogramming of the immune microenvironment, the use of such nanoparticles has the potential for future clinical applications.
Article by Algamri et al. Systematic Delivery of an Adjuvant CXCR4–CXCL12 Signaling Inhibitor Encapsulated in Synthetic Protein Nanoparticles for Glioma Immunotherapy is published in the journal ACS Nano.
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