PHOMULDNAPOL

Photoresponsive multifunctional DNA block copolymer nanocarriers for drug delivery and vaccine development

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 Obiettivo del progetto (Objective)

'Cancer treatment and vaccine development represent two of the major challenges that contemporary medicine is confronted with. Although significant progress has been achieved in both fields, the present methodologies remain limited, in part due to the numerous specific requirements for each treatment. This proposal focuses on the development of a novel, versatile drug delivery system suitable for either purpose, combining multifunctionality and controlled molecular release using biocompatible materials. The proposed approach involves the use of self-assembled nanocarriers based on amphiphilic DNA block copolymers with a photodegradable linker (PL) as a junction point (DNA-PL-Pol). These nanocarriers combine the advantageous features of the constituents of the DNA-PL-Pol, i.e. the possibility of attaching multiple functionalities by DNA hybridization, the localized and controlled release of encapsulants by near-infrared irradiation (NIR) and the biodegradability of the polymers. The project involves on one hand the synthesis of DNA-PL-Pol and the study of their aggregation behavior and on the other hand, the testing of the systems in cancer treatment and vaccine development. The proposed work will cover diverse fields in scientific research, i.e. organic and polymer synthesis, physical organic chemistry, supramolecular chemistry, biochemistry, cancer therapy and immunology.'

Introduzione (Teaser)

A European study developed a drug delivery system based on DNA. This innovative design boasts controlled release and biocompatibility and is also envisioned in vaccine applications.

Descrizione progetto (Article)

The development of effective drug delivery systems and vaccines remains a significant medical challenge. When designing such systems, scientists need to consider various aspects crucial for their performance such as composition, functionalisation, morphology and release mechanism.

For in vivo applications, biodegradable block copolymers are a fundamental pre-requisite to yield harmless by-products easy to eliminate from the organism. However, the vast majority of delivery systems utilise spherical aggregates, which remain in circulation as they evade uptake by macrophages.

To overcome this problem, scientists on the EU-funded PHOMULDNAPOL (Photoresponsive multifunctional DNA block copolymer nanocarriers for drug delivery and vaccine development) project proposed to develop nanocarriers based on DNA polymers. This system relies on complementary DNA sequences linked to specific molecules that produce multifunctional polymers when hybridised. Disassembly can be induced under specific conditions, providing controlled release.

Polymers from polyethylene glycol and poly-?-caprolactone were synthesised and assembled into worm-like micelles containing known anti-cancer drugs. The disassembly of these micelles was studied in vitro and their efficacy was tested in an in vivo cancer mouse model. Mice bearing tumours were injected with the formulation and exhibited a significant reduction in tumour size, clearly indicating that cancer treatment was effective.

With respect to vaccines, nanoparticle-based systems deliver immune-stimulatory and co-stimulatory molecules to antigen presenting cells to trigger immune responses. The PHOMULDNAPOL consortium linked short single-stranded DNA molecules known as CpGs with polyanions to form micelles that contained the antigen for vaccination. The anti-tumour efficacy of this innovative vaccine was assessed in vivo with promising results.

The use of DNA as a means of drug or vaccine delivery constitutes a novelty and is a significant advancement in the field given the versatility it offers.