Therapeutic Response of Multifunctional Lipid and Micelle Formulation in Hepatocellular Carcinoma

Abstract

Hepatic stellate cells (HSCs), as an important part of the tumor microenvironment (TME), could be activated by tumor cells as cancer-associated fibroblasts (CAFs), thereby promoting the production of extracellular matrix (ECM) and favoring the development of tumors. Therefore, blocking the "CAFs-ECM" axis is a promising pathway to improve antitumor efficacy. Based on this, we developed a multifunctional nanosized delivery system composed of hyaluronic acid-modified pHsensitive liposomes (CTHLs) and glycyrrheic acid-modified nanomicelles (DGNs), which combines the advantages of targeted delivery, pH-sensitivity, and deep drug penetration. To mimic actual TME, a novel HSCs+BEL-7402 cocultured cell model and a m-HSCs+H22 coimplanted mice model were established. As expected, CTHLs and DGNs could target CAFs and tumor cells, respectively, and promote the drug penetration and retention in tumor regions. Notably, CTHLs+DGNs not only exhibited a superior antitumor effect in three-level tumor-bearing mice but also presented excellent antimetastasis efficiency in lung-metastatic mice. The antitumor mechanism revealed that the lipid&micelle mixed formulations effectively inhibited the activation of CAFs, reduced the deposition of ECM, and reversed the epithelialmesenchymal transition (EMT) of tumor cells. In brief, the nanosized delivery system composed of CTHLs and DGNs could effectively improve the therapeutic effect of liver cancer by blocking the "CAFs-ECM" axis, which has a good clinical application prospect.

Glycyrrhizic Acid-Based Liposome for Tumor-Targeted Delivery of Cantharidin

“…Besides, the inhibition of GA−LP uptake by normal cells was observed to be relatively weak after the same concentration of GA treatment. 58 Herein, it was reasonable to infer that GA binding sites were expressed more in cancer cells than in normal cells, probably related to the overproliferation and the higher rate of surface receptor recycling regeneration of cancer cells.…”

Mixed Nanoscale Liposomes Co-Encapsulating Curcumin and Berberine Inhibit Activated Hepatic Stellate Cell-Induced Drug Resistance and Tumor Metastasis

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Enhancing the Inhibition of Breast Cancer Growth Through Synergistic Modulation of the Tumor Microenvironment Using Combined Nano-Delivery Systems

“…AIM-Chol was synthesized as previously described. 41 A solution comprising 120 mg of phospholipid (PL), 30 mg of cholesterol, 10 mg of AIM-Chol, and 4 mg of chondroitin sulfate-modified conjugates (DSPE-PEG-CS) were dissolved in ethanol, followed by the addition of Ber and Ru486 at varying concentrations (4 mg, 6 mg, and 12 mg each), respectively. Ethanol was subsequently removed through rotary evaporation at 60°C.…”