Recent advances in arsenic trioxide encapsulated nanoparticles as drug delivery agents to solid cancers

Abstract

Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success. This review summarizes the past and current utilization of arsenic trioxide in the medical field with primary focus on the implementation of nanotechnology for arsenic trioxide delivery to solid cancer cells. Different approaches that have been employed to increase arsenic's efficacy, specificity and bioavailability to solid cancer cells were evaluated and compared. The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry is proposed and discussed.

Local delivery of arsenic trioxide nanoparticles for hepatocellular carcinoma treatment

“…8 However, it is difficult to achieve effective As 2 O 3 accumulation inside a solid tumor because of rapid clearance of this drug in blood circulation. 9,10 A high dose can be used to maintain the therapeutic activity but causes systemic adverse reactions. Many studies have aimed to determine how to maintain a therapeutic As 2 O 3 concentration within target solid tumor tissue for an extended period of time with few systemic adverse reactions has been the aim of the most studies.…”

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

“…This can also lead to deactivation of the drug as these organoarsenic drugs react readily with blood proteins, in particular transferrin [ 10 ]. In order to limit premature inactivation of the arsenic drugs, a range of nanoparticles have been developed to enhance stability, thus increase activity [ 11 – 12 ]. These nanoparticles have been decorated with targeting ligands to enhance the accumulation of the drug in cancer tissue.…”

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal

“…However, two clinical trials showed synergistic treatment of TACE and ATO on HCC had better efficacy on preventing metastases and prolonging survival (Wang et al., 2015 ; Hu et al., 2017 ). The low solubility and quick elimination of ATO from blood stream are the main reasons that limit ATO to have adequate chemotherapeutic effect at the tumor site (Akhtar et al., 2017 ). On the other hand, people are reluctant to use high dose of ATO for prolonged period.…”

“…Nanoparticles and microspheres are effective tools for sustained drug delivery and multiple studies on ATO nanoparticles and microspheres have shown improved antitumor effects (Zhou et al., 2005 ; Yang et al., 2009 ; Zhou et al., 2012 ; Kalepu & Nekkanti, 2015 ; Akhtar et al., 2017 ; Ellison et al., 2017 ; Lu et al., 2018 ; Duan et al., 2019 ; Hu et al., 2019 ; Lian et al., 2019 ; Wu et al., 2020 ). The drug loading of ATO and its releasing pattern in these particles are essential for therapeutic efficacy.…”

“…Many materials, including liposome, polymersomes, magnetic complex, albumin, and silica, have been used to optimize the constructs. Nevertheless, the low solubility of ATO is still an obstacle for achieving high drug load (Yang et al., 2009 ; Akhtar et al., 2017 ). Chemoembolization with drug eluting bead would be an ideal application of ATO microsphere since this procedure can locoregionally deliver drug to tumor and largely avoid the systemic exposure.…”