Incorporation of a rhodamine B conjugated polymer for nanoparticle trafficking both in vitro and in vivo.

Polymeric nanoparticles as drug delivery systems have the potential to improve the therapeutic efficacy and reduce the toxicity of chemotherapeutic drugs by enhancing the drug selectivity in vivo. The efficacy is directly dependent on the polymeric nanoparticles' in vivo fate. Therefore, it is very important to develop a method to stably label the polymeric nanoparticles for detecting the in vivo fate. Here, we report a method to stably label self-assembled nanoparticles by the incorporation of rhodamine B-conjugated poly(ε-caprolactone) (PCL-RhoB). Only 1% of PCL-RhoB was released from the RhoB-labeled polymeric nanoparticles (RhoB-PNPs) in phosphate buffer within 12 hours, which suggested that the signal of PCL-RhoB can be used to represent the behaviors of polymeric nanoparticles both in vitro and in vivo. PCL-RhoB could be effectively extracted and quantitatively detected by ultra-high-performance liquid chromatography (UPLC) in various media, such as PBS, a cell culture medium containing 10% FBS (pH = 7.4 and pH = 6.8), mouse serum, simulated intestinal fluid and cell or tissue lysis. The intracellular contents of PCL-RhoB in MDA-MB-231 cells detected by UPLC were linearly correlated to the concentration of the RhoB-PNPs. In addition, the contents of PCL-RhoB in plasma and the spleen were proportional to the injected dose of RhoB-PNPs in vivo. As an application example, the pharmacokinetics and biodistribution of the nanoparticles over time in vivo were analyzed following intravenous injection to confirm the feasibility of this method.