Anti-tumor Drug Loaded Liquid PFOB Nanocapsules With Hyaluronic Acid Decoration

Despite the most advanced medical technology nowdays, cancer constructs aserious threat to human health and life. Chemical therapy based on drug deliverysystem is the most promising treatment for most cancer patients. The application ofultrasound contrast agents (UCAs) can significantly improve the sensitivity andcontrast of disease ultrasound diagnosis by providing higher quality ultrasound,enlarges the application range of ultrasound imaging. Most UCAs have goodproperties to combine other diagnosis agent or therapy agent for the developing oftheranostics agent. While traditional UCAs have larger size and lack of tissuetargeted specificity, PFOB nano-sized UCAs are easier to penetrate into the tissues.Under receptor-mediated endocytosis, Hyaluronic acid (HA) can be efficient uptakeby tumor cells and realize tumor active targeting. We used the PFOB nanocapsulesas nano-sized UCAs and nano-sized drug delivery system (NDDS), integratingultrasound imaging and chemotherapy in combination, used HA as active targetingmolecule，developed a novel multifunctional contrast agent which could realizesimultaneous targeted diagnosis, drug delivery, and therapeutic monitoring.The PFOB encapsulated PLA nanocapsules (PFOB@PLA NCs) as bothnano-sized UCAs and NDDS were generated by the oil-in-water (W/O/W) emulsionmethod using biocompatible and biodegradable poly(lactic acid)(PLA) to loadperfluorooctyl bromide (PFOB). The HA were deposited on the surface ofPFOB@PLA NCs via electrostatic adsorption to form hyaluronic acid decoratedPFOB@PLA NCs (PFOB@PLA/HA NCs). The result of potential indicated thesuccessful deposition of HA and the result of EDS indicated the successfulencapsulation of PFOB. The average diameter of spherical composite NCs wasabout300nm which satisfied the size demand of enhanced permeability andretention effect (EPR). hyaluronic acid decorated PFOB and DOX co-encapsulatedPLA nanocapsules (PFOB+DOX@PLA/HA NCs) as NDDS had high encapsulationefficiency and high drug loading efficiency and good release properties. The R6Glabeled composite NCs (PFOB+R6G@PLA/HA NCs) could be efficient intracellularuptake by Hela cells with a lower uptake by HUVECs, and could selectivelyaccumulated into the tumor site owing to both passive accumulation via the EPReffect and active targeting by the strong receptor-binding affinity of HA to CD44with high specificity, suggesting a good tumor targeted properties. The compositeNCs were proved to have great capabilities of ultrasound contrast enhancement bothin vitro and in vivo. The cell viablilty assay indicated that PFOB@PLA/HA NCs had good biocompatible and PFOB+DOX@PLA/HA NCs selectivly killed the Helacells.In conclusion, we developed a multifunctional composite NCs which couldrealize simultaneous tumor targeted ultrasound imaging, tumor targeted drugdelivery, and therapeutic monitoring. This composite might have a certain greatpotential in the clinical application of cancer theranostic.