Nanoparticles in cancer therapy

Nanoterapeutici (1-100 nm) predstavljaju mogućnost unapređenja terapije karcinoma. Zbog svojih jedinstvenih karakteristika imaju brojne prednosti u odnosu na konvencionalnu kemoterapiju od kojih je najbitnija potencijal ciljane dopreme lijeka do tumorskog tkiva čime se postiže manja sistemska toksičnost koja je najistaknutiji nedostatak konvencionalne kemoterapije. Nanočestice mogu pasivno doprijeti do tumora kroz propusnu vaskulaturu koja okružuje tumor zahvaljujući učinku povećane permeabilnosti i retencije. Kod aktivne ciljane dostave ligandi, koji se vežu za određene receptore koji su prekomjerno eksprimirani u tumorskim stanicama ili tumorskoj vaskulaturi su vezani za površinu nanočestice u kojoj je uklopljen lijek. Nanočestice osjetljive na podražaj reagiraju na fizikalne, kemijske, ili biološke podražaje koji promoviraju otpuštanje lijeka. Multifunkcionalne nanočestice posjeduju više korisnih svojstava, a posebna podskupina su teranostici koji omogućuju istovremenu dijagnozu i liječenje. U kliničkoj primjeni su različiti tipovi nanoterapeutika uključujuci virusne vektore, konjugate lijeka, lipidne nanočestice, polimerne nanočestice te anorganske nanočestice. Konjugati lijeka su trenutno najuspješniji nanoterapeutici u kliničkoj primjeni. Vecina klinički dostupnih nanoterapeutika su nanolijekovi prve generacije sa svojstvom pasivne ciljane dopreme. Da bi nanočestice došle do ciljanog mjesta, moraju izbjeći razgradnju u mononuklearnom fagocitnom sustavu i renalnu filtraciju te nakon ekstravazacije kroz krvne žile proći kroz tumorsku stromu gdje je prisutan visoki gradijent tlaka intersticijske tekućine te nakon toga stupiti u interakciju s ciljanim stanicama ili otpustiti lijek koji će ostvariti farmakološki efekt. Stoga je za optimalnu dopremu potrebno optimizirati ne samo fizikalno-kemijske karakteristike nanočestica, nego i mikrookolinu tumora.Nanotherapeutics (1-100 nm) represent an opportunity of improving the treatment of cancer. Due to its unique characteristics, nanotherapeutics have many advantages over conventional chemotherapy. The most important advantage is the potential of targeted delivery of drugs to the tumor tissue resulting in lower systemic toxicity which is the most prominent disadvantage of conventional chemotherapy. Nanoparticles can passively reach the tumor tissue through the leaky vasculature surrounding the tumor due to the increased permeability and retention effect. In active targeting, targeting ligands are attached at the surface of the nanocarrier for binding to appropriate receptors overexpressed by the tumor cells or tumor vasculature and not expressed by the normal cells. Stimuli-sensitive nanocarriers respond to physical, chemical, or biological stimuli that promote the release of the drug. Multifunctional nanocarriers have several useful properties. Theranostics are an emerging subset of multifunctional nanomedicine compounds which provide both the diagnosis and treatment with the same nanoformulation. Various types of nanomedicine compounds have been used in clinical cancer care, including viral vectors, drug conjugates, lipidbased nanocarriers, polymer-based nanocarriers, and inorganic nanoparticles. At present, the most successful nanomedicine therapeutics in clinical cancer care are drug conjugates. Most clinically available nanocarrier-based cancer therapeutics are passively targeted first-generation nanomedicine drugs. In order to reach the target site, noparticles have to avoid degradation by the mononuclear phagocyte system and renal filtration, extravasate into tumor compartment, travel through the tumor stroma against high interstitial fluid pressure gradients, and then interact with target cells or release the drug payload for pharmacological effect. Therefore, it is necessary for optimal delivery to optimize not only the physico-chemical properties of the nanoparticles, but also the tumor microenvironment