Dual-Targeted Hyaluronic Acid/Albumin Micelle-Like Nanoparticles for the Vectorization of Doxorubicin

Abstract

Drug targeting of tumor cells is one of the great challenges in cancer therapy; nanoparticles based on natural polymers represent valuable tools to achieve this aim. The ability to respond to environmental signals from the pathological site (e.g., altered redox potential), together with the specific interaction with membrane receptors overexpressed on cancer cells membrane (e.g., CD44 receptors), represent the main features of actively targeted nanoparticles. In this work, redox-responsive micelle-like nanoparticles were prepared by self-assembling of a hyaluronic acid–human serum albumin conjugate containing cystamine moieties acting as a functional spacer. The conjugation procedure consisted of a reductive amination step of hyaluronic acid followed by condensation with albumin. After self-assembling, nanoparticles with a mean size of 70 nm and able to be destabilized in reducing media were obtained. Doxorubicin-loaded nanoparticles modulated drug release rate in response to different redox conditions. Finally, the viability and uptake experiments on healthy (BALB-3T3) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a drug vector in cancer therapy.

Albumin–Hyaluronan Interactions: Influence of Ionic Composition Probed by Molecular Dynamics

“…The interaction between albumin and hyaluronate in the presence of various species such as water and ions is an interesting issue that is closely related to the unique properties of synovial systems. A second important reason for the interest in these systems is associated with the drug delivery enhancement abilities of various albumin-hyaluronan nanoparticles [26,27,[36][37][38][39]. However, to the best of the authors knowledge there is very limited information about the structural features of albumin-hyaluronan molecular assemblies, including intermolecular interaction characteristics.…”

Dynamic covalent crosslinked hyaluronic acid hydrogels and nanomaterials for biomedical applications

“…This includes conjugation of cystamine using the traditional carbodiimide method that was used as a functional handle to incorporate other hydrophobic groups such as docosahexaenoic acid (DHA) and chlorin e6 (Ce6), which induced self-assembly 94 . Cystamine was also conjugated at the reducing-end of HA that was later conjugated to the NHS modified albumin to give HA-cystamine-albumin conjugate that formed micelle-like nanoparticles 95 . Similarly, alkyne moiety was incorporated at the reducing end of HA that was used to conjugate poly trimethylene carbonate-co-dithiolane trimethylene carbonate (P(TMC-co-DTC) by click chemistry that yielded self-assembled nanoparticle formation.…”

Marine Polysaccharides as a Versatile Biomass for the Construction of Nano Drug Delivery Systems

“…To achieve a controlled release of the pendant, cleavable bonds will be introduced into the DDS. For example, disulfide bonds or imine bonds were introduced between the functional molecules and the polysaccharide backbone to realize the response release of the tumor microenvironment [ 85 , 86 , 87 ].…”