Novel multifunctional nanoparticles for combined photodynamic and conventional cancer therapy

Specificity is a critical feature of a cancer treatment and efforts are devoted to develop powerful strategies improving this aspect. Nanothechnology offers a great opportunity in cancer treatment based on the concept that a drug formulated in nanoparticles can alter its pharmacokinetics improving the treatment ability to target and kill cells of diseased tissues/organs while affecting as few healthy cells as possible. Another advantage of nanoparticles relies on sustained release of the entrapped anti-cancer drug which results in a prolongation of drug plasma half-life and reduction of administration in the patients. Furthermore, it has been suggested that drug accumulation and slow release inside tumour cells can be useful to circumvent MDR. Nanotechnological approaches as been proposed also in adjuvant therapy for cancer such as photodynamic therapy (PDT) in an attempt to improve the specificity of the photoactive species (PS). On this basis, the final aim of this project is to design, formulate and test novel multifunctional nanoparticles combining conventional chemotherapy with PDT in the treatment of cancer. Nanoparticles will be prepared from two amphiphilic materials which have demonstrated a great potential in the nanodelivery of anticancer drugs after intravenous administration that is amphiphilic cyclodextrins and biodegradable amphiphilic copolymers of poly(ecaprolactone)/ poly(ethyleneoxide). The first formulative approach we would like to attempt is to physically entrap both PS and anticancer drug in nanoparticles based on amphiphilic copolymers which were demonstrated to interact differently with tumor cells. In parallel, we will try to prepare nanoparticles for cancer therapy containing a physically entrapped conventional drug from newly synthesized light-sensitive smart materials. Amid PS, we will focus on the class of porphyrins whereas Docetaxel will be the conventional chemotherapeutics employed to obtain “the proof of concept”. Nanosystems will need to be engineered to avoid reticular endothelial system (RES) recognition and passively target solid tumors through EPR effect. Nanoparticles will be also surface-modified with specific “homing groups” able to recognize receptors overexpressed in cancer cells (especially folates) to realize an actively targeted system. Technologically optimized nanoparticles will be tested on in vitro-stabilized tumor cell lines derived from breast cancer, prostate cancer, neck and head cancer and lung cancer to evaluate their activity at molecular level. The mode of interaction of nanoparticles with cells will allow a full comprehension on the mechanisms underlying nanodelivered drug activity and will make use of confocal scanning microscopy and fluorescence-activatedcell sorting.