The high presence of M2 macrophages has been reported to be closely associated with HCC

The high presence of M2 macrophages has been reported to be closely associated with HCC.78 M2 macrophages release IL-6, IL-1 and TNF- pro-tumor metastasis factors. Introduction With the quick increase in the incidence and mortality of liver malignancy, it has become a major public health problem worldwide. Btk inhibitor 2 It is estimated that more than one million people will suffer from liver malignancy annually by 2025.1 Btk inhibitor 2 Liver malignancy is reportedly the sixth most common malignancy and the fourth leading cause of cancer-related death worldwide in 2018.2 Hepatocellular carcinoma (HCC) is the most common type of main liver cancers, accounting for about 90% of all main liver cancers worldwide.3 The HCC prevalence varies geographically and it is the most common cause of death in patients with cirrhosis. HCC occurs in the setting of chronic liver inflammation and it is significantly associated with chronic viral hepatitis contamination (hepatitis B or C), alcohol, or toxins. The inflammatory microenvironment provides a favorable growth environment for the HCC development and promotes the abnormal transformation of normal liver cells, such as hepatocytes, stem cells, immune cells and stellate cells.4,5 The tumor microenvironment (TME) is the internal and external environment for tumor development, which plays an important role in tumorigenesis, immune escape and treatment resistance. TME contributes to tumor evasion of immune acknowledgement in three main ways: (1) allowing malignancy cells to proliferate massively by suppressing the immune response of the Btk inhibitor 2 microenvironment; (2) inducing angiogenesis to promote tumor growth under hypoxic conditions; and (3) promoting immune escape of malignancy cells.6 The HCC microenvironment exhibits a stronger immunosuppressive effect compared with other tumors, with almost all cellular subpopulations and numerous regulatory mechanisms contributing to the HCC progression. Therefore, the importance of TME in the HCC treatment has received increasing attention in recent years, which drives TME-based researches. Nano-delivery systems can deliver numerous chemotherapeutic drugs, therapeutic genes, and Btk inhibitor 2 photothermal reagents to tumors, thus effectively reducing drug toxicity and resistance, increasing their solubility and improving the targeting ability of therapeutic brokers.7,8 Diverse types of designed nanoparticles have been developed to deliver therapeutic agents to solid tumors. They can protect therapeutic brokers from degradation, and the enhanced permeability and retention (EPR) effect facilitates their preferential accumulation at tumors.9 However, passive targeting based on the EPR effect is inefficient and often prospects to unpredictable clinical outcomes.9,10 Therefore, researchers have developed the modified nanoparticles to actively target tumor sites. For example, the nanoparticles altered with folic acid could improve their uptake by tumor cells.11 The modified nanoparticles interacted with TME have exhibited encouraging results in the HCC treatment. They kill tumor cells by specifically identifying HCC cells and targeting the HCC microenvironment to release therapeutic agents. Given the important role that TME plays in the occurrence and progression of HCC, it is of great significance to regulate TME in the HCC treatment. Nano-delivery systems deliver therapeutic agents to regulate TME is a very effective means in that it can affect the HCC progression by regulating signaling pathways, angiogenesis and immune cells. The purpose of this evaluate is to make a comprehensive summary of researches on nano-delivery systems for modulating the HCC microenvironment, in order to gain a better understanding about the relevant TME components in the HCC progression and how nanoparticles modulate Rabbit Polyclonal to PC these components. In this review article, we mainly focus on nanoparticles that modulate the HCC microenvironment. We first describe the TME components of HCC and their impact on HCC progression, then discuss the TME- and immune system-related nanoparticles in the HCC treatment, and finally provide an overview on the remaining difficulties. HCC and TME The HCC microenvironment is composed of malignancy cells and stromal cells, including fibroblasts, endothelial cells, macrophages and lymphocytes,12C14 each cell type plays its unique function. The extracellular matrix (ECM) provides a growth environment for these cells. All these intercellular communications ultimately determine how HCC progress. The components of the HCC microenvironment and their functions are shown below (Physique 1). Open in a separate window Physique 1 The tumor microenvironment components of HCC and their impact on the HCC progression. Abbreviations: CAF, cancer-associated fibroblast; ECM, the extracellular matrix; MDSC, myeloid-derived suppressor cell; TAM, tumor-associated macrophage; CTL, cytotoxic T cell; Treg, regulatory T cell; DC, dendritic cell. Fibroblasts are found in fibrous matrices, where they participate in wound repair, tissue maturation and.

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