RHSA-SS-PCL Nanocarriers For Cancer Drug Delivery:Synthesis, Characterization And Anticancer Studies

Human serum albumin (HSA) is a natural carrier delivering hydrophobic molecules in the body. During the past few decades, HSA has become a hotspot in drug delivery research own to its nontoxic, non-immunogenic, and biocompatible characters. The enhanced uptake of albumin-based nanoparticles in solid tumors is mediated by the enhanced permeability and retention (EPR) effect, which exists in most tumor tissues. And the the receptors on the microvessel endothelial cells or cancer cells can further initiated the particles’ cellular enrichment through its transcytosis.Doxorubicin (DOX) is an anthracycline antibiotic showing a strong broad-spectrum inhibition to cancer cells. It is commonly used to treat cancers of the breast, lung, ovary and others in clinic. However, the doxorubicin treatments can induce adverse effects, such as life-threatening heart damage. Therefore, developing a proper drug delivery system to reduce the side effects and keep the anticancer capacity is one of the most important tasks currently.We utilized recombinant HSA and PCL to develop a novel, biodegradable materials, rHSA-SS-PCL. It formed micelles spontaneously in aqueous solution with a diameter of around80nm. The micelles were reductant responsed when dealt with DTT. Doxorubicin was successfully loaded into rHSA-SS-PCL micelles with a high drug-loading (8.16%) and entrapment efficiency (88.82%) when the feed ratio was10%. rHSA-SS-PCL/DOX showed significant cell inhibition to various human cancer cell lines including Bcap37, A549, HepG2. Due to the SPARC-mediated endocytosis, the uptake of rHSA-SS-PCL/DOX was faster than PGE-PCL/DOX. In vivo studies showed that rHSA-SS-PCL/DOX could target solid tumor through active or passive ways, exhibiting excellent antitumor activities and high safety. Parts of rHSA-SS-PCL/DOX uptook by other tissues, like liver, could be degraded directly and expelled by urine to avoid unexpected side effects. Further rHSA-SS-PCL/DOX antitumor experiments carrying with BALB/c nude mice bearing human tumor xenografts showed the equivalent antitumor efficiency with free DOX, and overcame the various drawbacks of free DOX. What’s more, PEG modification by chemical or physical methods could prolong the circulation time of rHSA-SS-PCL micelles in vivo.