Nanocarriers deliver anti-cancer therapeutics
Chemotherapy constitutes the gold standard of cancer treatment. However, research into the mechanisms of tumour development has revealed specific overexpressed proteins that could be targeted therapeutically. Nanotechnology is expected to overcome the limitations of traditional chemotherapeutics through the targeted delivery of anticancer agents to cancer cells. Well-designed drug delivery systems can escape macrophage capture, prolonging drug circulation in the blood and increasing the possibility of targeting the tumour. The EU-funded NANOPHOTO (Targeted nanosystems for improving photodynamic therapy and diagnosis of cancer) project developed nanocarriers to improve the pharmacokinetics, biodistribution and therapeutic efficacy of a drug used in photodynamic therapy (PDT). PDT utilises photosensitising drugs and light to kill cells by producing reactive oxygen species (ROS). NANOPHOTO researchers focused on the drug meta-tetrahydroxyphenyl chlorine (mTHPC) that is used to treat head and neck squamous cell carcinoma. Scientists experimented with various nanocarriers including liposomes as well as the more recently developed PLGA copolymer and organically modified silica (ORMOSIL) nanoparticles. The mTHPC drug was successfully loaded into the nanoparticles with no apparent perturbations of its photophysical properties and ability to produce ROS. In addition, researchers increased the stealth properties of the drug-carrying nanoparticles by coating their surface with a layer of polyethylene glycol (PEG). Overall, the PEGylated nanoparticles improved the pharmacokinetics of the entrapped mTHPC. Following intravenous administration into tumour-bearing animals, this system increased mTHPC bioavailability compared to the standard formulation. Liposome formulations improved mTHPC tumour uptake and selectivity, reducing adverse side effects of PDT. Importantly, the increased uptake rate of this formulation is expected to shorten hospitalisation time of cancer patients and healthcare costs. The next step is to manufacture clinical grade liposomal mTHPC formulation and initiate clinical trials. The NANOPHOTO project demonstrated the capacity of nanoparticles to specifically and safely deliver anti-cancer drugs. The capacity to further functionalise nanoparticles with surface molecules opens up new avenues for anti-cancer therapy.
Keywords
Cancer, NANOPHOTO, photodynamic therapy, mTHPC, liposome