title: Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect.
abstract: Targeted cancer therapies are currently a strong focus in biomedical research. The most common approach is to use nanocarrier-based targeting to specifically deliver conventional anticancer drugs to enhance their therapeutic efficacy, increase bioavailability, and decrease the side-effects on normal cells. A step further towards higher specificity and efficacy would be to employ specific novel drugs along with specific nanocarrier-based targeting. Our recent studies have demonstrated that a plant-derived diterpenoid compound, anisomelic acid (AA), induces apoptosis in cervical cancer cells. In this work, we describe the development of a folic acid (FA)-targeted AA delivery system using chitosan-coated rod-shaped mesoporous silica particles (Chitosan-NR-MSP). The cellular internalization and uptake enhancement of the FA-Chitosan-NR-MSP towards cancerous folate receptor (FR)-positive (SiHa and HeLa) and/or normal FR-negative (HEK 293) cells were assessed, which indicated that the intracellular uptake of FA-conjugated Chitosan-NR-MSP was more target-specific. Furthermore, the induction of apoptosis by AA-loaded chitosan-coated rod-shaped particles on SiHa cells was studied. By employing caspase-3 activation and PARP cleavage as measure of apoptosis, the FA-particle mediated AA treatment was clearly more effective, significantly enhancing apoptosis in comparison to non-targeted Chitosan-NR-MSP or free AA in SiHa cells, suggesting that the FA-Chitosan-NR-MSPs can be potentially utilized as a drug delivery system for cervical cancer treatment.
authors.affiliation: Department of Biosciences, Cell biology, Åbo Akademi University, Tykistokatu 6B, FI-20520 Turku, Finland. john.eriksson@abo.fi.
authors.forename: Rajendran
authors.initials: R
authors.lastname: Senthilkumar
authors.forename: Didem Şen
authors.initials: DŞ
authors.lastname: Karaman
authors.forename: Preethy
authors.initials: P
authors.lastname: Paul
authors.forename: Emma M
authors.initials: EM
authors.lastname: Björk
authors.forename: Magnus
authors.initials: M
authors.lastname: Odén
authors.forename: John E
authors.initials: JE
authors.lastname: Eriksson
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosenholm
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000737:chemistry* / Q000378:metabolism*; D048271:Chitosan / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C000613048:anisomelic acid; D012822:Silicon Dioxide; D048271:Chitosan; D053148:Caspase 3