<p>Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy</p>

Abstract

BackgroundThe tumor-targeting ability and pH-sensitive properties of intelligent drug delivery systems are crucial for effective drug delivery and anti-tumor therapy.MethodsIn this study, sHA-DOX/HA-GA mixed micelles were designed with the following properties: sulfated hyaluronic acid (sHA) was synthesized to block cell migration by inhibiting HAase; sHA-DOX conjugates were synthesized via pH-sensitive hydrazone bond to realize DOX-sensitive release. The introduction of HA-GA conjugate could improve active-targeting ability and cellular uptake.ResultsThe results showed that the mixed micelles possessed a nearly spherical shape, nanoscale particle size (217.70±0.89 nm), narrow size distribution (PDI=0.07±0.04), negative zeta potential (−31.87±0.61 mV) and pH-dependent DOX release. In addition, the sHA-DOX/HA-GA micelles exhibited concentration-dependent cytotoxicities against liver carcinoma cells (HepG2) and HeLa cells, and were shown to be effectively taken up by HepG2 cells by confocal microscopy analysis. Furthermore, the in vivo anti-tumor study showed that mixed micelles had a superior anti-tumor effect compared to that of free DOX. Further evidence obtained from the hematoxylin–eosin staining and immunohistochemistry analysis also demonstrated that sHA-DOX/HA-GA exhibited stronger tumor inhibition and lower systemic toxicity than free DOX.ConclusionThe sHA-DOX/HA-GA mixed micelles could be a potential drug delivery system for anti-hepatoma therapy.

Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis

“…To observe the in vivo biodistribution of dual-ligand-modified Lip, hepatoma-bearing mice model was established by subcutaneous injection 0.1 mL of H22 cells suspension into the BALB/c mice. 36 When the tumor volume reached about 150 mm 3 , the mice were divided into three groups and intravenously injected with free DiR, DiR/Lip or DiR/GA&Gal-Lip. The DIR biodistribution in mice was investigated using in vivo imaging system at 1, 2, 4, 8, 12, 24, 48 and 72 h after injection.…”

The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…Polymeric micelles exhibited a high capacity to incorporate various bioactive molecules such as antisense oligonucleotides, plasmid DNA, proteins, small interfering ribonucleic acids (siRNAs), messenger RNAs [ 247 ]. Micelles could offer positive liver-targeting, mainly for anticancer agents [ 246 , 248 , 249 ], with further research needed in the anti-MAFLD future.…”

Biomaterials for protein delivery for complex tissue healing responses

“…We have described a variety of approaches to enhance proteinbiomaterial interactions for effective protein delivery. However, there are many other strategies to improve the efficacy of protein delivery for tissue repair that rely on mediating the interactions between the biomaterials and surrounding tissue, including tissue targeting, 114 tissue mimicry, 115 and stimuliresponsive materials. These strategies increase the ability of a biomaterial to respond to changes in the surrounding tissue that occur during injury and healing.…”

“…Biomaterials fabricated with specific ligands or binding partners enable a material delivered locally to bind specifically to a target cell or tissue, 114,116 thereby enhancing local material retention. Biomaterials containing target receptors 63,114 or synthetic peptides 94,116,117 have been fabricated to bind to a variety of tissues.…”

“…Biomaterials fabricated with specific ligands or binding partners enable a material delivered locally to bind specifically to a target cell or tissue, 114,116 thereby enhancing local material retention. Biomaterials containing target receptors 63,114 or synthetic peptides 94,116,117 have been fabricated to bind to a variety of tissues. A common approach is to target abundant ECM in the tissue of interest, which has been pursued with both collagen-binding domains for targeting biomaterials to bone, 118 solid tumors, 119 inflammatory sites, 91 and hyaluronic acid-binding domains for targeting tumors 120,121 and cartilage.…”