RESUMO
This research aimed at the key issue that chemical drugs and Chinese medicine hydrophilic small molecule anti-tumor drugs were difficult to break through the dense interstitial permeability barrier of pancreatic cancer to achieve the key problem of drug efficacy in the deep part of tumor tissue. To solve this problem, the lipophilic molecule squalene (SQ) and the hydrophilic anti-tumor drug chidamide (CHI) were linked by a trypsin responsive bond to form a prodrug (SQ-CHI) and a folic acid modified prodrug self-assembled nanoparticles (FA-SQ-CHI NPs) were further developed. The feature of prodrug molecules and nanoparticles were characterized. The in vitro release characteristics and cytotoxicity of blank vector were investigated. The efficacy and permeability of the prodrug nanoparticles in the PSN-1 monolayer cell and PSN-1/HSPC co-cultured tumor spheroids model was evaluated. The results showed that SQ-CHI prodrug molecules and FA-SQ-CHI NPs were successfully developed. The nanoparticles were regular spherical, well-dispersed, with a particle size of (173.3 ± 1.5) nm, a drug load of (59.02 ± 0.8) % and showed trypsin responsive release ability. The prodrug nanoparticles can significantly enhance the penetration and anti-proliferation effects of CHI in the PSN-1/HSPC tumor spheroids. In conclusion, the construction of folic acid-modified SQ-CHI prodrug self-assembled nanoparticles can significantly enhance the penetration of CHI in the pancreatic cancer microenvironment in vitro. This research would provide a new idea for the construction of targeted drug delivery system for chemical drugs and Chinese medicine hydrophilic small molecule drugs in the application of anti-pancreatic cancer.
RESUMO
OBJECTIVE: Insulin-like grouth factor-1 (IGF-1) is polypetide hormone that has demonstrated effects on neural cells. Up to now, there is few reports about the relation between serum IGF-1 and brain damage in neonates with hyperbilirubinemia. This study explored the potential role of serum IGF-1 in neonatal hyperbilirubinemia. METHODS: Serum levels of IGF-1 were measured using ECLIA in 57 term neonates with hyperbilirubinemia and 25 normal term neonates. Meanwhile, total serum bilirubin (TSB), unconjugated bilirubin (USB) and serum albumin (ALB) contents were measured by the automatic biochemistry analyzer and the ratio of USB/ALB (B/A) was calculated. The hyperbilirubinemia group was classified into three subgroups based on serum TSB levels: mild (221-256 micromol/L), moderate (257-342 micromol/L) and severe (>342 micromol/L). Serum TSB levels in the 25 normal neonates were less than 85 micromol/L (control group). NBNA was performed on the day of serum sample collection. RESULTS: Serum IGF-1 levels in the mild, moderate and severe hyperbilirubinemia groups (39.38+/- 8.42, 30.77+/- 4.65 and 26.34+/- 2.05 ng/L, respectively) were obviously lower than those in the control group (50.16+/- 15.73 ng/L) (P< 0.01). There were significant differences among the three hyperbilirubinemia subgroups in serum IGF-1 levels (P< 0.01). Mean NBNA scores in the mild, moderate and severe hyperbilirubinemia groups (35.01+/- 2.26, 32.45+/- 2.74 and 26.77+/- 5.02, respectively) were significantly lower than those in the control group (38.24+/- 0.78) (P< 0.01). Significant differences in the NBNA scores were noted among the three hyperbilirubinemia subgroups (P< 0.01). Serum IGF-1 levels were positively correlated to NBNA scores (r=0.603, P< 0.01) and negatively correlated to the ratio of B/A (r=-0.483, P< 0.01). CONCLUSIONS: Serum IGF-1 levels decreased obviously in neonates with hyperbilirubinemia and correlated to the severity of disease. IGF-1 might be associated with bilirubin-induced brain damage.
