POLYTRIGG

"Bioactive block copolymer vesicles as pH-triggerable, nano particulate carriers for cancer vaccination"

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 Obiettivo del progetto (Objective)

'Advanced designed vaccines have to combine proper antigen with the effective immune-stimulating agents (adjuvants) and delivery strategies in order to attain successful treatment. Presently, most vaccines are given as liquid formulations by intramuscular administration. However, nano-sized carriers of antigens hold great promise to be more effective delivery systems. To achieve the desired anti-cancer therapy; the ideal antigen nano-carrier has to fulfil a number of requirements. First of all carriers need to be (hollow) particles like with diameters in the range 50-500 nm in order to be taken up by dendritic cells (antigen-presenting cells capable to induce immune response). To facilitate the development of cellular immune responses, vaccine antigen must be presented on MHC (Major Histocompatibility Complex) class I. To win the goal, the nano-carrier should selectively bind to these cells, and be taken up into endosomes. To doing this carriers should be able to display certain adjuvants as targeting and stimulating ligands on their surface, and be capable to release its cargo upon response to pH changes in the endosome. Furthermore, vesicles have to carry and release antigen (i.e. proteins) to target destination with minor side-effects (biocompatibility and non-toxicity of carrier are essential). Hence, it is the goal of proposed project to develop nano-carriers on the basis of block copolymer vesicles (polymersomes) that have all those features. The aim is to developed polymersomes based on amphiphilic poly(2-methyloxazoline) PMOXA or (polydimethysiloxane) PDMS blocks in combination with stimulus-responsive copolymers blocks and a tunable polymersome surface chemistry. Therefore, the final goal is to provide 'smart' drug delivery system with versatile surface chemistry, which will allow the attachment/incorporation of different adjuvants (e.g. saponins) and consequently enable target delivery.'

Introduzione (Teaser)

Many drugs necessitate intracellular delivery to be effective. In answer to this, a European study developed a series of novel nanomaterials for delivery of anticancer drugs.

Descrizione progetto (Article)

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.