Nanomedicine‐boosting icaritin-based immunotherapy of advanced hepatocellular carcinoma

Abstract

Traditional treatments for advanced hepatocellular carcinoma (HCC), such as surgical resection, transplantation, radiofrequency ablation, and chemotherapy are unsatisfactory, and therefore the exploration of powerful therapeutic strategies is urgently needed. Immunotherapy has emerged as a promising strategy for advanced HCC treatment due to its minimal side effects and long-lasting therapeutic memory effects. Recent studies have demonstrated that icaritin could serve as an immunomodulator for effective immunotherapy of advanced HCC. Encouragingly, in 2022, icaritin soft capsules were approved by the National Medical Products Administration (NMPA) of China for the immunotherapy of advanced HCC. However, the therapeutic efficacy of icaritin in clinical practice is impaired by its poor bioavailability and unfavorable in vivo delivery efficiency. Recently, functionalized drug delivery systems including stimuli-responsive nanocarriers, cell membrane-coated nanocarriers, and living cell-nanocarrier systems have been designed to overcome the shortcomings of drugs, including the low bioavailability and limited delivery efficiency as well as side effects. Taken together, the development of icaritin-based nanomedicines is expected to further improve the immunotherapy of advanced HCC. Herein, we compared the different preparation methods for icaritin, interpreted the HCC immune microenvironment and the mechanisms underlying icaritin for treatment of advanced HCC, and discussed both the design of icaritin-based nanomedicines with high icaritin loading and the latest progress in icaritin-based nanomedicines for advanced HCC immunotherapy. Finally, the prospects to promote further clinical translation of icaritin-based nanomedicines for the immunotherapy of advanced HCC were proposed.

Icaritin Derivative IC2 Induces Cytoprotective Autophagy of Breast Cancer Cells via SCD1 Inhibition

“…In contrast, traditional Chinese medicine is multi-targeted, has low toxicity and is highly utilizable to selectively kill tumor cells and have a higher safety profile, making it an ideal choice for antitumor drug development. ICT is one of the active ingredients of the Chinese herb Epimedium Genus , and has been approved as a novel treatment for advanced hepatocellular carcinoma, demonstrating its efficacy, safety and broad therapeutic potential [ 19 ]. ICT truly exerts anti-hepatocellular carcinoma activity through various mechanisms including apoptosis, cell cycle regulation, anti-angiogenesis, anti-metastasis and immunomodulation [ 32 , 33 ].…”

“…Epimedium Genus is derived from the Berberidaceae family and is used as a traditional Chinese medicine to strengthen the muscles and bones, tonify kidney yang and dispel wind and dampness [ 18 ]. ICT can be extracted from the dry stems and leaves of Epimedium Genus directly or produced by hydrolyzing the other major flavonoids in Epimedium Genus [ 19 ]. Several methods including column chromatography, chemical synthesis, and acid and enzymatic hydrolysis have been developed for the production of ICT.…”

“…Furthermore, ICT displayed anticancer activities by inhibiting IL-6/JAK/STAT3 pathways in advanced hepatocellular carcinoma cells and enhancing the effector T cell function [ 27 ]. Recently, ICT was approved by the National Medical Products Administration of China for the treatment of advanced hepatocellular carcinoma [ 19 ]. However, whether ICT-based derivatives could also have a better performance in cancer treatment is unclear.…”

Prognostic Significance of the CXCLs and Its Impact on the Immune Microenvironment in Ovarian Cancer

“…OC patients were divided into high and low CXCL groups according to the median transcripts per million (TPM) expressions. The methods used in this study refer to Lu et al's previously published paper [ 12 ]. GSE66957 dataset contains mRNA expression profiles of 57 ovarian cancer and 12 normal ovarian samples.…”

Correction to: Nanomedicine‐boosting icaritin-based immunotherapy of advanced hepatocellular carcinoma

“…Following publication of the original article [ 1 ], it was found there are some errors in the article.…”