Heat-responsive nanomagnetic drug carrier for site-specific pancreas cancer therapy
In 2021, 235,000 people in Germany died as a result of cancer. This makes cancer the second most common cause of death in Germany. For tumours like pancreatic cancer with high risk of early metastasis, conventional cancer therapies are mainly limited to systemic chemotherapy treatment causing severe side effects and having low therapeutic success. The 5-year survival rate of those affected is just 7 %. The cytostatic drugs used for pancreatic carcinoma serve less to cure the disease and more to provide palliative care to enable the patient to survive a few years with an improved quality of life. To reduce whole body exposition to the drug and raise the local drug concentration, controlled drug guidance and release is necessary.
In order for cytostatic drugs to be effective locally and in high doses, a targeted method of application of these active substances is required. Approaches to the precise and individualizable therapy of cancer are being researched in the field of nanomedicine. With the help of magnetic nanoparticles (MNP), low side-effect, personalized and precise therapies are being developed. The MNP and cytostatic drugs are loaded inside biodegradable thermo-responsive poly-(lactide-co-glycolide) acid (PLGA) nanospheres. By application of a combination of static and alternating magnetic fields, the PLGA nanospheres can be accumulated at the tumour site and then heated inducing hyperthermia (> 43 °C) and temperature-controlled local drug release. This offers the possibility of a controllable combination therapy of hyperthermia and chemotherapy, which can be applied in a targeted and individualised manner by means of specialised surface functionalizations, e.g.signal peptides.
For the success of these therapeutic approaches, it is indispensable that the magnetic drug carriers are enriched with high effectiveness in the pancreatic tumour and protected from physiological degradation processes for application via the blood. Both named properties are studied in a pancreatic cancer organoid system, which mimics the structure of the tumour. The organoid technology uses patient’s own tumour cells for recreation of a 3D in vitro model. This enables a highly personalized therapy of the tumour, thereby reducing the use of animals for these studies to zero.