Smart anticancer drugs
Most molecules including DNA, enzymes and antibiotics, require delivery inside the cell as they cannot cross the plasma membrane. As such, when using these molecules as drugs, it is essential to facilitate their transport. This is usually achieved by nanoparticles that can bind to and release the active compound within the cell in a controlled manner. When it comes to cancer, the increased permeability of tumour vessels often cause small anticancer drugs to escape easily. If encapsulated in a nanoparticle, these drugs would have an increased chance of successfully reaching their target. An ideal drug-delivery system should be biocompatible, non-toxic and able to respond to a certain stimulus such as the pH for drug release. Given the low pH of the cancer microenvironment, pH responsiveness is a valid approach for targeting tumours. The EU-funded POLYTRIGG project set out to develop a new generation of nanostructures for efficient delivery of drugs to tumour cells. The work of the consortium focused on the compound polyoxazoline (POXA), which is similar to the widely used polyethylene glycol. The advantage of POXA lies in its capacity to change its hydrophilic and hydrophobic properties, leading to a variety of synthetic possibilities. During the project, a number of nanoparticles were synthesised that displayed excellent cell viability and could release the anticancer drug doxorubicin in response to a pH drop from 7.4 to 5.5. In addition, the particles demonstrated endosomal escape, indicating efficient intracellular targeting. Taken together, the results of the POLYTRIGG study provide a promising tool for intracellular drug delivery. The versatile surface chemistry of the generated polymers could be exploited to alter the properties and hence the target of the delivery platform.
Keywords
Anticancer drugs, intracellular delivery, nanomaterials, cancer, low pH
