RESUMO
Improving the anticancer efficacy of chemotherapeutic drugs and photosensitizers requires innovative multifunctional nanoplatforms. This study introduces a chemo- and phototherapeutic drug delivery system (DDS) based on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), both PEGylated and non-PEGylated, with a mean size of 200 ± 75 nm. Colchicine (Colch) and purpurin18 (P18) were co-encapsulated into these NPs, and their in vitro drug release profiles were investigated. The anticancer potential of these systems was evaluated across various cell lines (i.e., CaCo-2, PC-3, MCF-7, and MRC-5 cells), demonstrating enhanced NP uptake by cancer cells compared to free drugs. Co-administration of Colch and P18 in 2D and 3D cell line models exhibited a synergistic effect, harnessing both chemotherapeutic and photodynamic effects, leading to higher cancer cell elimination efficacy. This newly developed multifunctional DDS presents a promising platform for combined chemo- and photodynamic therapy in cancer treatment.
Assuntos
Colchicina , Portadores de Fármacos , Liberação Controlada de Fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Humanos , Colchicina/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Portadores de Fármacos/química , Linhagem Celular Tumoral , Esferoides Celulares/efeitos dos fármacos , Nanopartículas/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Neoplasias/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodosRESUMO
Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.
