RESUMO
BACKGROUND: Recent evidence has been demonstrated that Sinomenine (SIN) exerts antitumor activity in vitro. However, the clinical utility of SIN remains limited mainly because of its poor bioavailability. Exosomes are nanoscale vesicles that play crucial roles in intracellular communications through functionally active substances such as DNA and RNA. Exosomes have been utilized as nanocarriers for targeted drug delivery of different anticancer drugs. METHODS: The present study aimed to evaluate the effectiveness of combined Exosomes-SIN for the treatment of hepatocellular carcinoma (HCC) in a rat model. To do so, we prepared a mixture of SIN and exosomes (Exo-SIN) to improve the bioavailability of SIN to treat liver cancer. The in vitro releasing profile of the Exo-SIN was examined. RESULTS: We observed a continuous, slow release of SIN from Exo-SIN in simulated body fluid as well as tumor microenvironment. In the cytotoxicity test, Exo-SIN exhibited a significantly stronger inhibition in HepG2 cells compared to free SIN. The flow cytometry assessments showed that Exo-SIN could suppress HepG2 cell migration in a Transwell assay and induce cell cycle arrest and cellular apoptosis. Western blotting showed that survivin, a crucial protein for the survival of living cells, was significantly downregulated after treatment with Exo-SIN. CONCLUSION: In conclusion, our data suggested that Exo-SIN could serve as a potential, effective delivery platform for hepatic carcinoma therapy.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Neoplasias Hepáticas/tratamento farmacológico , Morfinanos/farmacologia , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Exossomos/química , Humanos , Neoplasias Hepáticas/patologia , Morfinanos/química , Ratos , Ratos Sprague-DawleyRESUMO
To achieve improved drug delivery efficiency to hepatocellular carcinoma (HCC), biodegradable poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NP), surface-modified with SP94 peptide, were designed for the efficient delivery of cryptotanshinone to the tumor for the treatment of HCC. Cryptotanshinone NP and SP94-NP were prepared by using nanoprecipitation. The physicochemical and pharmaceutical properties of the NP and SP94-NP were characterized, and the release kinetics suggested that both NP and SP94-NP provided continuous, slow release of cryptotanshinone for 48 h. The in vitro cellular experiment demonstrated that SP94-NP significantly enhanced the cellular uptake of cryptotanshinone and induced high cytotoxicity and cellular apoptosis of hepatocellular carcinoma (HepG2) cells. The in vivo detecting results of targeting effect using the Cy5.5 probe evidenced that SP94-NP showed an accumulation in tumor more efficiently than that of unconjugated ones. Meanwhile, SP94-NP exhibited the smallest tumor size than other groups and showed no toxicity to body. The results of this study provide a promising nanoplatform for the targeting of HCC.