Arsenic trioxide (ATO) is one of the first-line chemotherapeutic drugs for acute promyelocytic leukemia. Its anti-cancer activities against various human neoplastic diseases have been extensively studied. However, the clinical use of ATO for solid tumors is limited, and these limitations are because of severe systemic toxicity, low bioavailability, and quick renal elimination before it reaches the target site. Although without much success, several efforts have been made to boost ATO bioavailability toward solid tumors without raising its dose. It has been found that nanomedicines have various advantages for drug delivery, including increased bioavailability, effectiveness, dose-response, targeting capabilities, and safety as compared to traditional drugs. Therefore, nanotechnology to deliver ATO to solid tumors is the main topic of this review, which outlines the previous and present medical applications of ATO. We also summarised ATO anti-cancer mechanisms, limitations, and outcomes of combinatorial treatment with chemo agents. As a result, we strongly recommend conducting pre-clinical and clinical studies of ATO, especially nano-system-based ones that might lead to a novel combination therapy for cancer treatment with high efficacy, bioavailability, and low toxicity for cancer patients.

/pdf/current-advances-of-nanomedicines-delivering-arsenic-27ju2bao.pdf

Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy

Mineral drugs are an important constituent of traditional Chinese medicine (TCM). Taking minerals that contain heavy metals as drugs is a very national characteristic part of TCM. However, the safety and scientific nature of mineral drugs are controversial owing to their heavy metals and strong toxicity. In 2000, the Food and Drug Administration (FDA) authorized arsenic trioxide (ATO) as first-line therapy for acute promyelocytic leukemia. This makes the development and utilization of mineral drugs become a research hotspot. The development of nanomedicine has found a great prospect of mineral drugs in nano-delivery carriers. And that will hold promise to address the numerous biological barriers facing mineral drug formulations. However, the studies on mineral drugs in the delivery system are few at present. There is also a lack of a detailed description of mineral drug delivery systems. In this review, the advanced strategies of mineral drug delivery systems in tumor therapy are summarized. In addition, the therapeutic advantages and research progress of novel mineral drug delivery systems are also discussed. Here, we hope that this will provide a useful reference for the design and application of new mineral drug delivery systems. 

/pdf/mineral-medicine-from-traditional-drugs-to-multifunctional-3eexmd3f.pdf

Mineral medicine: from traditional drugs to multifunctional delivery systems

Controlled electrochemical growth of micro-scaled As2O3 and Ga2O3 oxide structures on p-type gallium arsenide

To assess the clinical value of drug-eluting bead trans-arterial chemoembolization (DEB-TACE) combined with microwave ablation (MWA) vs. MWA treatment alone for early stage hepatocellular carcinoma (HCC). Consecutive data from 102 HCC patients at early stage who were referred to our hospital from December 2014 to May 2016 were retrospectively collected. Forty-seven patients underwent DEB-TACE combined with MWA treatment, whereas 55 patients underwent MWA alone. After 1 month of treatment, the tumour responses of the patients were assessed using the mRECIST criteria. Treatment-related complications and hepatic function were also analysed for the two groups. In addition, overall survival (OS) and progression-free survival (PFS) were calculated and compared. Patients in the combined treatment group (DEB-TACE combined with MWA) presented a better objective response rate (ORR) and disease control rate (DCR) compared with those in the monotherapy group (MWA treatment). The median OS and PFS were longer in the combined treatment group compared with the monotherapy group. Multivariate Cox’s regression further illustrated that DEB-TACE + MWA vs. MWA was an independent protective factor for PFS and OS. No serious treatment-related complications were observed in any of the patients. Combined treatment with DEB-TACE appeared to have advantages in prolonging OS and PFS compared to MWA. Therefore, combined treatment was efficient and should be strongly recommended to early stage HCC patients.

/pdf/drug-eluting-bead-trans-arterial-chemoembolization-combined-4sjs2lc14w.pdf

Drug-eluting bead trans-arterial chemoembolization combined with microwave ablation therapy vs. microwave ablation alone for early stage hepatocellular carcinoma: a preliminary investigation of clinical value

The application of arsenic trioxide in cancer: An umbrella review of meta-analyses based on randomized controlled trials.

Chemoembolization for hepatocellular carcinoma (HCC) is often suboptimal due to multiple involved signaling and lack of effective drugs. Arsenic trioxide (ATO) is a potent chemotherapeutic agent, which can target multiple signaling and have substantial efficacy on HCC. However, its usage is limited due to systemic toxicity. Using ATO-eluting beads/microspheres for chemoembolization can have locoregional drug delivery and avoid systemic exposure but will require high drug load, which has not been achieved due to low solubility of ATO. Through an innovative approach, we generated the transiently formed ATO microcrystals via micronization and stabilized these microcrystals by solvent exchange. By encapsulating ATO microcrystals, but not individual molecules, with poly(lactide-co-glycolic acid) (PLGA), we developed microspheres cored with extremely high dense ATO. The molar ratio between ATO and PLGA was 157.4:1 and drug load was 40.1%, which is 4-20 fold higher than that of reported ATO nano/microparticles. These microspheres sustainably induced reactive oxygen species, apoptosis, and cytotoxicity on HCC cells and reduced tumor growth by 80% via locoregional delivery. Chemoembolization on mice model showed that ATO-microcrystal loaded microspheres, but not ATO, inhibited HCC growth by 60-75%, which indicates ATO within these microspheres gains the chemoembolizing function via our innovative approach.

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal.

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Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal.