Liver cancer is a highly lethal malignant tumor with a high incidence worldwide. Therefore, its treatment has long been a focus of medical research. Although traditional treatment methods such as surgery, radiotherapy, and chemotherapy have increased the survival rate of patients, their efficacy remains unsatisfactory owing to the nonspecific distribution of drugs, high toxicity, and drug resistance of tumor tissues. In recent years, the application of nanotechnology in the medical field has opened a new avenue for the treatment of liver cancer. Among these treatment methods, photothermal therapy (PTT) based on nanoliposomes has attracted wide attention owing to its unique targeting and high efficiency. This article reviews the latest preclinical research progress of nanoliposome-based PTT for liver cancer and its metastasis, discusses the preclinical challenges in this field, and proposes directions for improvement, with the aim of improving the effectiveness of liver cancer treatment.

Arsenic agents have shown great potential in fighting leukemia, but are poorly known in treating solid tumors, mainly ascribing to the rapid clearance and low targeting ability. It is reported that morphology modulation can enhance the interaction between nanoparticles and cell membrane. Herein, a dismountable protein corona-modified virus-like manganese-arsenic nanomedicine (vMnAs@HR) is rationally proposed for realizing safe and targeted delivery and synergistic arsenotherapy. The virus-like manganese-arsenic nanoparticle (vMnAs) is constructed followed by modification of a temporary R848-loaded HDL (HR) protein corona. Upon intravenous injection, the HR protein corona is stable and actively targeted to tumor tissue by taking advantage of the interaction between HDL and its receptor SR-BI. Intriguingly, upon accumulated in the tumor, HR can be jettisoned and interacted with macrophages for proinflammatory phenotype modulation. The re-exposed vMnAs can efficiently enhance endocytosis by taking advantage of the rationally designed spiky morphology. Moreover, the released double-stranded DNA (dsDNA) and manganese ions during tumor cell apoptosis can cooperatively activate cyclic guanosine monophosphate adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway of DCs for systematic immune activation. It is anticipated that this morphology-transformable nanomedicine can realize safe and efficient arsenic delivery for synergistic arsenotherapy.

Arsenic trioxide (ATO) has gained significant attention due to its promising therapeutic effects in treating different diseases, particularly acute promyelocytic leukemia (APL). Its potent anticancer mechanisms have been extensively studied. Despite the great efficacy ATO shows in fighting cancers, drawbacks in the clinical use are obvious, especially for solid tumors, which include rapid renal clearance and short half-life, severe adverse effects, and high toxicity to normal cells. Recently, the emergence of nanomedicine offers a potential solution to these limitations. The enhanced biocompatibility, excellent targeting capability, and desirable effectiveness have attracted much interest. Therefore, we summarized various nanocarriers for targeted delivery of ATO to solid tumors. We also provided detailed anticancer mechanisms of ATO in treating cancers, its clinical trials and shortcomings as well as the combination therapy of ATO and other chemotherapeutic agents for reduced drug resistance and synergistic effects. Finally, the future study direction and prospects were also presented.

Arsenic has been an element of great interest among scientists for many years as it is a widespread metalloid in our ecosystem. Arsenic is mostly recognized with negative connotations due to its toxicity. Surely, most of us know that a long time ago, arsenic trioxide was used in medicine to treat, mainly, skin diseases. However, not everyone knows about its very wide and promising use in the treatment of cancer. Initially, in the seventies, it was used to treat leukemia, but new technological possibilities and the development of nanotechnology have made it possible to use arsenic trioxide for the treatment of solid tumours. The most toxic arsenic compound - arsenic trioxide - as the basis of anticancer drugs in which they function as a component of nanoparticles is used in the fight against various types of cancer. This review aims to present the current solutions in various cancer treatment using arsenic compounds with different binding motifs and methods of preparation to create targeted nanoparticles, nanodiamonds, nanohybrids, nanodrugs, or nanovehicles.

In recent years, the use of arsenic trioxide (ATO) in the context of ovarian cancer chemotherapy has attracted significant attention. However, ATO's limited biocompatibility and the occurrence of severe toxic side effects hinder its clinical application. A nanoparticle (NP) drug delivery system using ATO as a therapeutic agent is reported in this study. Achieving a synergistic effect by combining starvation therapy, chemodynamic therapy, and chemotherapy for the treatment of ovarian cancer was the ultimate goal of this system. This nanotechnology-based drug delivery system (NDDS) introduced arsenic-manganese complexes into cancer cells, leading to the subsequent release of lethal arsenic ions (As3+) and manganese ions (Mn2+). The acidic microenvironment of the tumor facilitated this process, and MR imaging offered real-time monitoring of the ATO dose distribution. Simultaneously, to produce reactive oxygen species that induced cell death through a Fenton-like reaction, Mn2+ exploited the surplus of hydrogen peroxide (H2O2) within tumor cells. Glucose oxidase-based starvation therapy further supported this mechanism, which restored H2O2 and lowered the cellular acidity. Consequently, this approach achieved self-enhanced chemodynamic therapy. Homologous targeting of the NPs was facilitated through the use of SKOV3 cell membranes that encapsulated the NPs. Hence, the use of a multimodal NDDS that integrated ATO delivery, therapy, and monitoring exhibited superior efficacy and biocompatibility compared with the nonspecific administration of ATO. This approach presents a novel concept for the diagnosis and treatment of ovarian cancer.

As2O3 has shown significant anti-gastric cancer effects, but the mechanism is still unclear. Thus, biomacromolecular changes induced by As2O3 were investigated by using human gastric cancer AGS cells as the model. Flow cytometry results confirmed that As2O3 induced AGS cells apoptosis. Fourier transform infrared (FTIR) microspectroscopy detected biomacromolecular changes during As2O3-induced AGS cells apoptosis sensitively: IR spectra showed significant changes in the lipids content and the proteins and DNA structure. Peak-area ratios indicated obvious changes in the lipids and DNA content and the proteins structure, while also showing a relatively good linear relationship between A1733/A969 and the apoptosis rate. PCA exhibited significant alteration in nucleic acids while curve fitting further revealed the changes in nucleic acids and proteins. On the whole, our study explored As2O3-induced gastric cancer cells apoptosis in depth on the basis of analyzing biomacromolecular changes, in addition, it also suggested FTIR microspectroscopy to be possibly useful in the research of apoptosis.

Drug delivery is an important topic that has attracted the attention of researchers in recent years. Albumin nanoparticles play a significant role in drug delivery as a carrier due to their unique characteristics. Albumin is non-toxic, biocompatible, and biodegradable. Its structure is such that it can interact with different drugs, which makes the treatment of the disease faster and also reduces the side effects of the drug. Albumin nanoparticles can be used in the diagnosis and treatment of many diseases, including cancer, diabetes, Alzheimer's, etc. These nanoparticles can connect to some compounds, such as metal nanoparticles, antibodies, folate, etc. and create a powerful nanostructure for drug delivery. In this paper, we aim to investigate albumin nanoparticles in carrier format for drug delivery application. In the beginning, different types of albumin and their preparation methods were discussed, and then albumin nanoparticles were discussed in detail in diagnosing and treating various diseases.

Prussian blue (PB) nanoparticles have been widely used in photothermal therapy research due to the efficient photothermal conversion ability. In this study, PB was modified with a bionic coating using a hybrid membrane of red blood cell membranes and tumor cell membranes to prepare bionic photothermal nanoparticles (PB/RHM), which can further improve the blood circulation ability and tumor targeting of the nanoparticles to achieve efficient photothermal therapy for tumor treatment. In vitro formulation characterization showed that PB/RHM was a monodisperse spherical core-shell structured nanoparticle with a diameter of 207.2 nm and effectively retained the cell membrane proteins. The in vivo biological evaluation results showed that PB/RHM could effectively accumulate into the tumor tissue, inducing a rapid temperature increase in the tumor site to 50.9 °C within 10 min, inhibiting tumor growth efficiently with a tumor inhibition rate of 93.56% and with good therapeutic safety. In summary, this paper provided a hybrid film-modified Prussian blue nanoparticle with efficient photothermal anti-tumor capacity and safety.

Ferroptosis has emerged as a therapeutic tactic to trigger cancer cell death driven by abnormal accumulation of reactive oxygen species (ROS). However, a single ferroptosis treatment modality is often limited. In this work, a combination therapy of ferroptosis and immunotherapy for cancer was proposed. Specifically, a versatile nanodrug was designed for the multiple treatment of hepatocellular carcinoma (HCC) by loading dihydroartemisinin (DHA) on Fe³⁺-doped MnO₂ nanosheets (Fe-MnO₂/DHA). Firstly, Fe-MnO₂/DHA was degraded by glutathione (GSH) in the tumor microenvironment (TME) to release Fe²⁺, Mn²⁺ and DHA, leading to aberrant ROS accumulation due to Fenton/Fenton-like reaction. Secondly, breakage of endoperoxide bridge from DHA was caused by Fe²⁺ to further induce oxidative stress. Thirdly, the depleted GSH promoted the inactivation of glutathione peroxidase 4 (GPX4), resulting in lipid peroxide (LPO) accumulation. The resulting LPO and ROS could induce ferroptosis and apoptosis of liver cancer cells. Furthermore, Fe-MnO₂/DHA mediated three-pronged stimulation of oxidative stress, resulting in high levels of targeted immunogenic cell death (ICD). It could enhance the infiltration of CD4⁺ T and CD8⁺ T cells, and promote macrophage polarization. DHA also acted as an immunomodulator to inhibit regulatory T cells (Tregs) for systemic antitumor. Overall, Fe-MnO₂/DHA presents a multi-modal therapy for HCC driven by ferroptosis, apoptosis and immune activation, significantly advancing synergistic cancer treatment.

Cancer is a complex disease associated with a combination of abnormal physiological process and exhibiting dysfunctions in multiple systems. To provide effective treatment and diagnosis for cancer, current treatment strategies simultaneously focus on various tumor targets. Based on the rapid development of nanotechnology, nanocarriers have been shown to exhibit excellent potential for cancer therapy. Compared with nanoparticles with single functions, multifunctional nanoparticles are believed to be more aggressive and potent in the context of tumor targeting. However, the development of multifunctional nanoparticles is not simply an upgraded version of the original function, but involves a sophisticated system with a proper backbone, optimized modification sites, simple preparation method, and efficient function integration. Despite this, many well-designed multifunctional nanoparticles with promising therapeutic potential have emerged recently. Here, to give a detailed understanding and analyzation of the currently developed multifunctional nanoparticles, their platform structures with organic or inorganic backbones were systemically generalized. We emphasized on the functionalization and modification strategies, which provide additional functions to the nanoparticle. We also discussed the application combination strategies that were involved in the development of nanoformulations with functional crosstalk. This review thus provides an overview of the construction strategies and application advances of multifunctional nanoparticles.

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.

Hepatocellular carcinoma (HCC) poses a severe threat to human health and economic development. Despite many attempts at HCC treatment, most are inevitably affected by the genetic instability and variability of tumor cells. Arsenic trioxide (ATO) has shown to be effective in HCC. However, time-consuming challenges, especially the optimal concentration in tumor tissue and bioavailability of ATO, remain to be overcome for its transition from the bench to the bedside. To bypass these issues, nanotechnology-based delivery systems have been developed for prevention, diagnosis, monitoring and treatment in recent years. This article is a systematic overview of the latest contributions and detailed insights into ATO-loaded nanocarriers, with particular attention paid to strategies for improving the efficacy of nanocarriers of ATO.