RESUMO
Controlled drug release systems can enhance the safety and availability but avoid the side effect of drugs. Herein, the concept of DNA complementary base pairing rules in biology is used to design and prepare a photothermal-triggered drug release system. Adenine (A) modified polydopamine nanoparticles (A-PDA, photothermal reagent) can effectively bind with thymine (T) modified Zinc phthalocyanine (T-ZnPc, photosensitizer) forming A-PDA = T-ZnPc (PATP) complex based on A = T complementary base pairing rules. Similar to DNA, whose base pairing in double strands will break by heating, T-ZnPc can be effectively released from A-PDA after near infrared irradiation-triggered light-thermal conversion to obtain satisfactory photodynamic-photothermal synergistic tumor treatment. In addition, PDA can carry abundant Gd3+ to provide magnetic resonance imaging guided delivery and theranostic function.
Assuntos
Pareamento de Bases/fisiologia , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Hipertermia Induzida/métodos , Neoplasias/terapia , Fotoquimioterapia/métodos , Adenina/química , Animais , Linhagem Celular Tumoral , Terapia Combinada , DNA Complementar/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos/genética , Sinergismo Farmacológico , Feminino , Humanos , Indóis/química , Isoindóis , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacocinética , Fototerapia/métodos , Polímeros/química , Ensaios Antitumorais Modelo de Xenoenxerto , Compostos de ZincoRESUMO
Despite exhibiting potent anticancer activity, the strong hemolytic properties of melittin (MEL) significantly restrict its delivery efficiency and clinical applications. To address this issue, we have devised a strategy wherein homologous dopamine (DA), an essential component of bee venom, is harnessed as a vehicle for the synthesis of MEL-polydopamine (PDA) nanoparticles (MP NPs). The ingenious approach lies in the fact that MEL is a basic polypeptide, and the polymerization of DA is also conducted under alkaline conditions, indicating the distinctive advantages of PDA in MEL encapsulation. Furthermore, MP NPs are modified with folic acid to fabricate tumor-targeted nanomedicine (MPF NPs). MPF NPs can ameliorate the hemolysis of MEL in drug delivery and undergo degradation triggered by high levels of reactive oxygen species (ROS) within solid tumors, thereby facilitating MEL release and subsequent restoration of anticancer activity. After cellular uptake, MPF NPs induce cell apoptosis through the PI3K/Akt-mediated p53 signaling pathway. The tumor growth inhibitory rate of MPF NPs in FA receptor-positive 4T1 and CT26 xenograft mice reached 78.04% and 81.66%, which was significantly higher compared to that in FA receptor-negative HepG2 xenograft mice (45.79%). Homologous vehicles provide a new perspective for nanomedicine design.