Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. Transcatheter arterial chemoembolization has become a common treatment modality for some patients with unresectable advanced HCC. Since the introduction of nanomaterials in 1974, their use in various fields has evolved rapidly. In medical applications, nanomaterials can serve as carriers for the delivery of chemotherapeutic drugs to tumour tissues. Additionally, nanomaterials have potential for in vivo tumour imaging. This article covers the properties and uses of several kinds of nanomaterials, focusing on their use in transcatheter arterial chemoembolization for HCC treatment. This paper also discusses the limitations currently associated with the use of nanomaterials.

The solid tumors provide a series of biological barriers in cellular microenvironment for designing drug delivery methods based on advanced stimuli-responsive materials. These intertumoral and intratumoral barriers consist of perforated endotheliums, tumor cell crowding, vascularity, lymphatic drainage blocking effect, extracellular matrix (ECM) proteins, hypoxia, and acidosis. Triggering opportunities have been drawn for solid tumor therapies based on single and dual stimuli-responsive drug delivery systems (DDSs) that not only improved drug targeting in deeper sites of the tumor microenvironments, but also facilitated the antitumor drug release efficiency. Single and dual stimuli-responsive materials which are known for their lowest side effects can be categorized in 17 main groups which involve to internal and external stimuli anticancer drug carriers in proportion to microenvironments of targeted solid tumors. Development of such drug carriers can circumvent barriers in clinical trial studies based on their superior capabilities in penetrating into more inaccessible sites of the tumor tissues. In recent designs, key characteristics of these DDSs such as fast response to intracellular and extracellular factors, effective cytotoxicity with minimum side effect, efficient permeability, and rate and location of drug release have been discussed as core concerns of designing paradigms of these materials.

Transcatheter arterial embolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC) patients while some HCC cases have shown resistance to TACE.

To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC.

The microarray datasets of TACE-treated HCC tissues, HCC and non-HCC tissues were collected by searching multiple public databases. The respective differentially expressed genes (DEGs) were attained via limma R package. Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response. TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE non-response. The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model. The prognostic value of the key genes was evaluated by Kaplan-Meier curve. Multivariate analysis was utilised to investigate the independent prognostic factor in key genes. Single-cell RNA (scRNA) sequencing analysis was conducted to explore the cell types in HCC. TACE refractoriness-related genes activity was calculated via AUCell packages. The CellChat R package was used for the investigation of the cell-cell communication between the identified cell types.

HCC tissues of TACE non-responders (n = 66) and TACE responders (n = 81), HCC (n = 3941) and non-HCC (n = 3443) tissues were obtained. The five key genes, DLG associated protein 5 (DLGAP5), Kinesin family member 20A (KIF20A), Assembly factor for spindle microtubules (ASPM), Kinesin family member 11 (KIF11) and TPX2 microtubule nucleation factor (TPX2) in TACE refractoriness-related genes, were identified. The five key genes were all up-regulated in the TACE non-responders group and the HCC group. High expression of the five key genes predicted poor prognosis in HCC. Among the key genes, TPX2 was an independent prognostic factor. Four cell types, hepatocytes, embryonic stem cells, T cells and B cells, were identified in the HCC tissues. The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells. Hepatocytes, as the providers of ligands, had the strongest interaction with embryonic stem cells that provided receptors.

Five key genes (DLGAP5, KIF20A, ASPM, KIF11 and TPX2) were identified as promoting refractory TACE. Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.

Hepatocellular carcinoma (HCC) has the sixth-highest new incidence and fourth-highest mortality worldwide. Transarterial chemoembolization (TACE) is one of the primary treatment strategies for unresectable HCC. However, the therapeutic effect is still unsatisfactory due to the insufficient distribution of antineoplastic drugs in tumor tissues and the worsened post-embolization tumor microenvironment (TME, e.g., hypoxia and reduced pH). Recently, using nanomaterials as a drug delivery platform for TACE therapy of HCC has been a research hotspot. With the development of nanotechnology, multifunctional nanoplatforms have been developed to embolize the tumor vasculature, creating conditions for improving the distribution and bioavailability of drugs in tumor tissues. Currently, the researchers are focusing on functionalizing nanomaterials to achieve high drug loading efficacy, thorough vascular embolization, tumor targeting, controlled sustained release of drugs, and real-time imaging in the TACE process to facilitate precise embolization and enable therapeutic procedures follow-up imaging of tumor lesions. Herein, we summarized the recent advances and applications of functionalized nanomaterials based on TACE against HCC, believing that developing these functionalized nanoplatforms may be a promising approach for improving the TACE therapeutic effect of HCC.

The process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials.

Hepatic malignancies remain a global challenge. Hepatocellular carcinoma (HCC) accounts for around 90% of patients with liver cancer and is the sixth most common neoplasm worldwide and the fourth leading cause of cancer-related death. However, the long-term prognosis for HCC remains far from satisfactory, with a late diagnosis and limited treatment. DOX has served as conventional chemotherapy with the longest history of use. Although conventional chemotherapy is being challenged by molecular therapy and immune therapy, there is renewed optimism and interest in both systematic and locoregional therapy. Combined chemotherapy is widely used in clinical practice. In specific terms, FOLFOX can serve as a first-line (category 2B) option as recommended by the 2021 NCCN guidelines, while the efficacy of LTLD plus RFA has been confirmed in the phase III HEAT study. These approaches have challenged the dominant status of molecular therapy in terms of health economics and they have potential benefits in Asia, where HBV-related hepatocellular carcinoma is prevalent. Moreover, locoregional chemotherapy can be achieved with TACE and HAIC (possibly involving FOLFOX, DOX, mitomycin C, cisplatin, epirubicin, etc.). TACE was officially recommended by the 2021 NCCN guidelines for patients with Child-Pugh class B liver disease. In addition, HAIC has demonstrated a potential advantage in preliminary clinical practice, although it hasn't been included in any guidelines. Hence, this review summarizes large-scale trials and studies examining the development and innovative use of chemotherapeutic agents. Mounting clinical evidence warrants an exploration of the efficacy of chemotherapy.