pH-responsive delivery vehicle based on RGD-modified polydopamine-paclitaxel-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles for targeted therapy in hepatocellular carcinoma

Abstract

A limitation of current anticancer nanocarriers is the contradiction between multiple functions and favorable biocompatibility. Thus, we aimed to develop a compatible drug delivery system loaded with paclitaxel (PTX) for hepatocellular carcinoma (HCC) therapy. A basic backbone, PTX-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) PHBV nanoparticle (PHBV-PTX-NPs), was prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine (PDA). The HCC-targeted arginine-glycine-aspartic acid (RGD)-peptide and PDA-coated nanoparticles (NPs) were combined through the Michael addition. Subsequently, the physicochemical properties of RGD-PDA-PHBV-PTX-NPs were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray spectroscopy. As expected, the RGD-PDA-PHBV-PTX-NPs showed robust anticancer efficacy in a xenograft mouse model. More importantly, they exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. Taken together, these results indicate that the RGD-PDA-PHBV-PTX-NPs are potentially beneficial for easing conflict between multifunction and biocompatible characters of nanocarriers.

Melanin and Melanin-Functionalized Nanoparticles as Promising Tools in Cancer Research—A Review

“…For instance, Wu et al developed RGD-modified polydopamine-paclitaxel-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) NPs, in which PDA served as a pH-sensitive coating able to enhance drug stability and avoid premature drug release. This nanosystem showed a higher PTX release rate in vivo at pH values of 5.0–6.5 (which are specific for inclusion bodies and lysosomes of cancer cells) than at physiological pH (7.4), suggesting an intelligent, controlled, and pH-dependent drug release [ 101 ]. An explanation in this regard might come from the ability of PDA to dissolve slowly in acidic conditions [ 141 ].…”

“…An explanation in this regard might come from the ability of PDA to dissolve slowly in acidic conditions [ 141 ]. Furthermore, the NPs improved the PTX solubility and enhanced its antitumor effect, while showing favorable biocompatibility [ 101 ].…”

PDA-Based Drug Delivery Nanosystems: A Potential Approach for Glioma Treatment

“…Due to the mild reaction conditions of Michael reaction and Schiff base, targets such as antibody polypeptide nucleoacid aptamers, which are unstable in organic solvents or reaction conditions, can be easily attached to PDA surfaces without losing their biological activity. 83 Some special physical and chemical methods can also be used to achieve targeted drug delivery, such as using PDA adhesion coating of iron, nickel, cobalt, and other metals and their oxides, as well as other magnetic substances. Further, under the guidance of local magnetic field in vitro NPs are directed to the tumor site, to achieve magnetic targeting, in order to reduce the systemic toxicity of drugs to the body.…”

Engineering nanotheranostic strategies for liver cancer

“…Second, the involvement of nanomaterials allows modification of drug behavior, and binding to the targeted ligand is an excellent solution to improve drug delivery and enhance the therapeutic effect of tumor inhibition. For example, Wu et al [ 31 ] described PTX-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) PHBV nanoparticles coated with polydopamine (PDA-PHBV-PTX-NPs) and modified by hepatocellular carcinoma (HCC)-targeted arginine-glycine-aspartic acid (RGD-peptide). As shown in Figure 2A , integrin αvβ3 or αvβ5 are overexpressed in liver cancer cells, and RGD is a specific ligand of integrin αvβ3/αvβ5.…”