RESUMO
Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study presents a novel nanotherapeutic targeted DDS developed through the self-assembly of an amphiphilic di-block copolymer to deliver the chemotherapy drug SN38 specifically to breast cancer cells. The vehicle was constructed from the PHPMA-b-PEAMA diblock copolymer synthesized via RAFT polymerization. A single emulsion method was then used to encapsulate SN38 within nanoparticles (NPs) formed from the PHPMA-b-PEAMA copolymer. The AS1411 DNA aptamer was covalently bonded to the surface of the micellar NPs, producing a targeted DDS. Molecular dynamics (MD) simulation studies were also performed on the di block polymeric system, demonstrating that SN38 interacted well with the di block. The in vitro results demonstrated that AS1411- decorated SN38-loaded HPMA NPs were highly toxic to breast cancer cells while having a minimal effect on non-cancerous cells. Remarkably, in vivo studies elucidated the ability of the targeted DDS to enhance the antitumor effect of SN38, suppressing tumor growth and improving survival rates compared to free SN38.
Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Mama , Portadores de Fármacos , Irinotecano , Micelas , Oligodesoxirribonucleotídeos , Polímeros , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/administração & dosagem , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Animais , Portadores de Fármacos/química , Polímeros/química , Irinotecano/administração & dosagem , Irinotecano/química , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/química , Linhagem Celular Tumoral , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Camundongos Endogâmicos BALB C , Camundongos , Simulação de Dinâmica Molecular , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células MCF-7RESUMO
A novel label-free and enzyme-free fluorescence aptasensing assay that uses Sybr Green I (SGI) as the signal indicator for the kanamycin determination was designed. An aptamer-complementary strand (Apt/CP) conjugate was formed, which provided the intercalation sites for SGI and, therefore, a considerable fluorescent signal. The introduction of the target led to the separation of Apt from CP due to the high affinity of Apt toward kanamycin. Hence, the suitable intercalation gaps reduced, which resulted in a decrease in the generated fluorescent signal. Under optimized conditions, a broad linear concentration range from 0.05 µM to 20 µM and a limit of detection of 11.76 nM were obtained, confirming the ability of the fabricated aptasensor for sensitive and specific kanamycin detection in real samples such as milk and human serum. The aptasensing method has the potential to be extensively employed in the food industry and veterinary science due to its simplicity, sensitivity, user-friendly, and capability of on-site detection of kanamycin.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Humanos , Canamicina , Fluorometria , Corantes , Técnicas Biossensoriais/métodos , Limite de DetecçãoRESUMO
Objectives: Known as natural nanovesicles, exosomes have attracted increased attention as biocompatible carriers throughout recent years, which can provide appropriate sources for incorporating and transferring drugs to desired cells in order to improve their effectiveness and safety. Materials and Methods: This study implicates the isolation of mesenchymal stem cells from adipocyte tissue (ADSCs) to acquire a proper amount of exosomes for drug delivery. As the exosomes were separated by ultracentrifugation, SN38 was entrapped into ADSCs-derived exosomes through the combination method of incubation, freeze-thaw, and surfactant treatment (SN38/Exo). Then, SN38/Exo was conjugated with anti-MUC1 aptamer (SN38/Exo-Apt), and its targeting ability and cytotoxicity towards cancer cells were investigated. Results: Encapsulation efficiency of SN38 into exosomes (58%) was significantly increased using our novel combination method. Furthermore, the in vitro results were indicative of the great cellular uptake of SN38/Exo-Apt and its significant cytotoxicity on Mucin 1 overexpressing cells (C26 cancer cells) without noticeable cytotoxicity on normal cells (CHO cells). Conclusion: The results propose that our approach developed an efficient method for loading SN38 as a hydrophobic drug into exosomes and decorating them with MUC1 aptamer against Mucin 1 overexpressing cells. So, SN38/Exo-Apt could be considered a great platform in the future for the therapy of colorectal cancer.