Cancer researchers now imagine that specializing in critical energy infrastructure of cancer cells – mitochondria – can provide a brand new treatment strategy that overcomes two essential ways to avoid destruction of the tumor.
To kill tumors, doctors use drugs to kill dishonest cells. However, due to the rapid growth of cancer cells and their ability to repair damaged DNA, tumors can quickly develop resistance to these drugs, sometimes spreading throughout the body of the process called metastasis.
Scientists in China imagine that each scenarios might be celebrated on the mitochondria of cancer cells.
Why mitochondria is a key weakening of cancer cells
Mitochondria are specialized structures inside cells that produce chemical energy required to keep the cell alive and functioning. According to Yanjuan GU at the University of Polytechnic in Hong Kong, recent studies analyzing mitochondria have revealed their potential as the purpose of anti -cancer therapy.
“Studies have shown that mitochondria does not have solid DNA repair mechanisms, which makes them susceptible to targeted therapies,” said GU.
Mitochondria are contained in a specialized double membrane in the cell. In these compartments there are machines that produce energy, in addition to a specialized DNA unit often known as mitochondrial DNA.
One of the effective treatment of cancer cells is the administration of drugs that damage DNA, which leads to cell death. But tumors often develop resistance because of their DNA repair ability. How does the lack of these repair tools in mitochondria prevents this.
Scientists from several institutions have found that mitochondria are needed for metastasis – the ability of tumors to spread to other parts of the body. Many mechanisms are still not fully understood, but it is believed that changes in cancer cell mitochondria activate metastatic routes by which the mitochondria of cancer cells may even be transferred to healthy immune cells. This transfer at the same time suppresses the immune response to the spread of cancer, while making it easier to spread.
Based on these findings, GU and her colleagues hypothesized that cancer cells focused on mitochondria could avoid resistance and prevention or slow metastasis. However, packing and supplying drugs to mitochondria is a challenge.
All drugs focused on the mitochondria of cancer must enter the cancer cell, after which accumulate in mitochondria – and nowhere else. To do that, medicines are packed in media called exosomes and specific excellent proteins called ligands are attached. Exosomes are structures related to membrane utilized by cells for transporting various molecules. Ligands take the surface of the exosome and recognize and bind to the membranes of cancer cells, allowing them to go inside.
Unfortunately, finding the right combination of exosome, ligand and medicine might be difficult, because each ingredient can chemically change the functioning of the other after combining into one structure.
Development of intelligent nanoparticles: oxa@ex-rd
To meet these challenges of GU and its team developed a nanoparticle platform consisting of several components, each of which has a particular job.
Known as OXA@ex-rd, it consists of an exosome, a peptide focused on cancer cells, molecules focused on mitochondrion called dequalinium and chemotherapy drugs of oxalipyltin. Chosen exos is often known as stable after injection into the bloodstream and is just not toxic to healthy tissue.
“[The targeting peptide] It is one of the most famous active target legands assessed pre -clinically and clinically and promises aiming at cancer cells, “explained GU. The next two guide Mitochondria specifically.
Importantly, dequalinium is positively charged, which performs two functions. In cancer cells, the difference is responsible on either side of the mitochondrial membrane – often known as transbonit potential – is way higher than normal cells, which implies positively charged particles easily cut and accumulate inside.
That is why dequalinium accumulates in mitochondria, bringing an anti -cancer drug with it. It can also be toxic to mitochondria and leads to mitochondria failures and cell death. Finally, oxalipilatin drugs are related to mitochondrial DNA, causing flaws and damage.
Together, these elements make up a powerful attack on the mitochondria of cancer cells.
To test the treatment of nanoparticles, mice with colorectal cancer were treated OXA@ex-rd. Then the team measured how well the drug entered the cancer mitochondria, in addition to a discount in tumor volume and spread from the colon and the rectum to the liver.
The results have shown that the drug was effectively amassed in tumor mitochondria and worked well to reduce the size of the tumor. Compared to the control groups, tumors in treated mice@ex-rd were much smaller, and after removing and examining they showed the highest amounts of dead cells and necrotic tumor tissue.
Experiments regarding the reduced spread of cancer to the liver have shown that compared to control groups receiving a salt solution or oxalipilatin alone, treatment with full oxa@exo-rd nanoparesia, reduces the speed of recent tumors in the liver to 86%.
A step towards more practical cancer treatment
In the case of GU and team, these results show that their combination of components forming the nanoparticle is correct. The package was successfully delivered to the mitochondria of cancer cells and acted as expected. But before this treatment becomes widespread, there are several obstacles left.
The team must assess the potential negative effects for healthy mitochondria and higher understand how different tumors will react to treatment. “Cancer cells show different potentials of the mitochondrial membrane,” said Gu, which implies that the drug could also be less efficient in some cancers. There are also problems with costs, scalability and regulation.
According to GU, there may be a couple of standardized frames for assessing nanodrug based on exos, especially in terms of immunogenicity and long -term toxicity.
“As for costs, designed OXA@ex-RD, as an exosse therapy, probably incurs higher costs in advance than conventional chemotherapy due to the complexity of the production of exosomes,” she said. This complexity also reduces the scalability of production, storage and transport of nanoparticles to cancer clinics.
Despite these challenges, “we think that OXA@ex-rd is promising, but requiring resources of approach to the treatment of chemo-resistant cancers,” said Gu. “While current methods, such as conventional chemotherapy, are more accessible, progress in engineering and exosome production can help fill the gap in terms of costs and scalability.”
