master's thesis
Nanoparticles in cancer therapy

Vesna Valentić (2015)
Sveučilište u Zagrebu
Farmaceutsko-biokemijski fakultet
Zavod za farmaceutsku tehnologiju
Metadata
TitleNanočestice u terapiji karcinoma
AuthorVesna Valentić
Mentor(s)Mario Jug (thesis advisor)
Abstract
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.
Keywordsnanotherapeutics nanoparticles cancer active targeting passive targeting ligands stimuli-responsice nanocarriers multifuntional nanocarriers viral vectors drug conjugates lipid-based nanocarriers polymerbased nanocarriers inorganic nanoparticles mononuclear phagocyte system extravasation
Parallel title (English)Nanoparticles in cancer therapy
Committee MembersMario Jug
Željka Vanić
Lidija Bach-Rojecky
GranterSveučilište u Zagrebu
Farmaceutsko-biokemijski fakultet
Lower level organizational unitsZavod za farmaceutsku tehnologiju
PlaceZagreb
StateCroatia
Scientific field, discipline, subdisciplineBIOMEDICINE AND HEALTHCARE
Pharmacy
Pharmacy
Study programme typeuniversity
Study levelintegrated undergraduate and graduate
Study programmePharmacy
Academic title abbreviationmag. pharm.
Genremaster's thesis
Language Croatian
Defense date2015-05-26
Parallel abstract (English)
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.
Parallel keywords (Croatian)nanoterapeutici nanočestice karcinom pasivna ciljana doprema aktivna ciljana doprema ligandi nanočestice osjetljive na podražaj multifunkcionalne nanočestice virusni vektori konjugati lijeka lipidne nanočestice polimerne nanočestice anorganske nanočestice mononuklearno fagocitni sustav ekstravazacija
Resource typetext
Access conditionAccess restricted to students and staff of home institution
Terms of usehttp://rightsstatements.org/vocab/InC/1.0/
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:163:277998
CommitterPetra Gašparac