Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma

Abstract

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy

“…4 B and C, DiD-NE displays dominant accumulation in liver over other organs. This is in accordance with common views that liver is the major organ with profound reticuloendothelial system for capturing and clearing nanoparticles from the blood circulation 38 . Furthermore, we excised the liver and analyzed the distribution of DiD-NE at cellular level.…”

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

“…Many PAs are designed to contain a β-sheet forming segment in order to promote their self-assembly into nanofiber structures. An injectable hydrogel was prepared based on palmitoyl-GNNQQNYKD-OH PA. Incorporation of the triptolide drug did not affect the hydrogel formation [ 46 ].…”

Recent Progress in the Design and Application of Supramolecular Peptide Hydrogels in Cancer Therapy

“…[156] These micelles could convert into fibrous nanostructure after reaching MDA-MB-231 tumor site with high MMP-9 expression and form DOX depot for localized therapy of cancer. In addition to DOX, other chemotherapeutics such as vincristine, [139] tanshinone IIA, [157] and triptolide [158] have also been physically encapsulated in SPHs for localized cancer therapy. These hydrogels maintained the concentrations of drugs within a suitable range, which greatly enhanced the efficacy and safety of chemotherapy.…”