Chondroitin sulfate-based redox-responsive nanoparticles for melanoma-targeted drug delivery

Abstract

The therapeutic efficacy of most chemotherapeutic drugs is hampered by low water solubility, poor stability, serious side effects, and lack of tumor selectivity. To solve these issues, chondroitin sulfate (CS)-based redox-responsive nanoparticles were developed. The amphiphilic polymer, CS-alpha-tocopherol succinate (TOS) (CS-CYS-TOS), was constructed by conjugating TOS on the CS backbone via cystamine (CYS) as a redox-sensitive linker, which could self-assemble to form polymeric nanoparticles in phosphate buffer saline (PBS). The resulting nanoparticles had low critical aggregation concentration (CAC) of 0.027–0.040 mg/mL, small size, and narrow size distribution. The docetaxel (DTX)-loaded nanoparticles were fabricated by the sonication method with high drug loading (DL) of 17.06% ± 0.97. The dynamic light scattering (DLS) and transmission electron microscope (TEM) had shown spherical nanoparticles with a size of 170.7 nm ± 2.8 and ~160 nm, respectively, and zeta potential of −26.5 mV ± 1.5. The results of the reduction-triggered disassembly behavior study and in vitro release study revealed the redox-sensitive potential of CS-CYS-TOS nanoparticles. The nanoparticles exhibited time-dependent qualitative and quantitative uptake by melanoma cells. The Sulforhodamine B (SRB) assay indicated the safety of carrier material and enhanced anti-tumor activity of DTX-loaded nanoparticles. The in vivo biological performance of nanoparticles in tumor-bearing mice was evaluated and DTX/CS-CYS-TOS nanoparticles were superior in terms of tumor volume inhibition than other formulations. This nanoparticulate system responded to the reducing conditions in tumor cells, released drugs quickly and thoroughly, thereby improved the efficacy of chemotherapy.