Cyclic arginine-glycine-aspartic acid-modified red blood cells for drug delivery:Synthesis and in vitro evaluation

Red blood cells(RBCs)are an excellent choice for cell preparation research because of their biocompatibility,high drug loading,and long half-life.In this study,doxorubicin(DOX)was encapsulated with RBCs as the carrier.The biotin-avidin system binding principle was used to modify biotinylated cyclic arginine-glycine-aspartic acid(cRGD)onto RBC surfaces for accurate targeting,high drug loading,and sustained drug release.The RBC drug delivery system(DDS)was characterized,and the concentration of surface sulfur in the energy spectrum was 6.330%.The physical and chemical properties of RBC DDS were as follows:drug content,0.857 mg/mL;particle size,3339 nm;potential value,12.5 mV;and cumulative release rate,81.35%.There was no significant change in RBC morphology for up to seven days.The results of the targeting and cytotoxicity studies of RBC DDS showed that many RBCs covered the surfaces of U251 cells,and the fluorescence intensity was higher than that of MCF-7 cells.The IC50 value of unmodified drug-loaded RBCs was 2.5 times higher than that of targeted modified drug-loaded RBCs,indicating that the targeting of cancer cells produced satisfactory inhibition.This study confirms that the RBC DDS has the characteristics of accurate targeting,high drug loading,and slow drug release,which increases its likelihood of becoming a clinical cancer treatment in the future.

Synthesis and evaluation of peptide-fentanyl analogue conjugates as dualμ/δ-opioid receptor agonists for the treatment of pain

Novel peptide-fentanyl analogue conjugates were synthesized by the covalent coupling of carfentanyl derivatives to the C-terminus or N-terminus of the conformationally constrained dermorphin tetrapeptide BVD03 via a chemical linker.The carfentanyl-related analogues displayed distinct binding and functional activities atμ/δopioid receptors(MOR/DOR)and antinociceptive effects when conjugated to the peptide.The most potent compound,SW-LJ-11,displayed mixed MOR/DOR agonist properties in the low nanomolar range and significant analgesic efficacy in vivo in four classic mouse models of pain.Interestingly,SW-LJ-11 did not exhibit any physical dependence or respiratory depression,in contrast to an equipotent analgesic dose of morphine or BVD03,indicating that the use of opioid peptide-fentanyl analogue conjugates as dual MOR/DOR agonists may be a promising strategy for obtaining safer opioids.