Recent Progresses in Cancer Nanotherapeutics Design Using Artemisinins as Free Radical Precursors

Abstract

Artemisinin and its derivatives (ARTs) are sort of important antimalarials, which exhibit a wide range of biological activities including anticancer effect. To solve the issues regarding poor solubility and limited bioavailability of ARTs, nanoformulation of ARTs has thus emerged as a promising strategy for cancer treatment. A common consideration on nanoARTs design lies on ARTs' delivery and controlled release, where ARTs are commonly regarded as hydrophobic drugs. Based on the mechanism that ARTs' activation relies on ferrous ions (Fe 2+ ) or Fe 2+ -bonded complexes, new designs to enhance ARTs' activation have thus attracted great interests for advanced cancer nanotherapy. Among these developments, the design of a nanoparticle that can accelerate ARTs' activation has become the major consideration, where ARTs have been regarded as radical precursors. This review mainly focused on the most recent developments of ARTs nanotherapeutics on the basis of advanced drug activation. The basic principles in those designs will be summarized, and a few excellent cases will be also discussed in detail.

GPX4 inhibition synergistically boosts mitochondria targeting nanoartemisinin-induced apoptosis/ferroptosis combination cancer therapy

“…8 Nanotechnology provides an alternative strategy to solve some physicochemical and pharmacokinetic problems, such as low water solubility, poor bioavailability and short half-life of artemisinin, and to improve the therapeutic efficacy of artemisinin to a certain extent in cancer treatment. [18][19][20][21][22][23] In many cases, ART assisted other drugs to realize excellent anticancer effects. [24][25][26][27][28][29] To date, the development of ART-based single drug nanoformulation remains a great challenge and no satisfactory ART single drug nanoformulation is available for highly efficient cancer therapy.…”

Tween 80 Micelles Loaded with Fe3O4 Nanoparticles and Artemisinin for Combined Oxygen-Independent Ferroptosis Therapy of Cancer

“…The synthesized iron oxide nanoparticles bore similarities to the IONP 4 synthesized by Hauksdóttir et al [37], characterized by their ultra-small particle size and hydrophobic properties. Furthermore, the average particle size of the TW80 micelles loaded with ART and Fe 3 O 4 NPs is smaller compared to that reported by Doost et al [38] and Sukmawati et al [39]. The former encapsulated plant-based oregano essential oil (OR) and transcinnamaldehyde (TCA) with an average size ranging from 92 to 337 nm, while the latter encapsulated doxorubicin (DOX) and curcumin analogs with an average size of 111.8 nm using TW80.…”

Artemisinin-Type Drugs in Tumor Cell Death: Mechanisms, Combination Treatment with Biologics and Nanoparticle Delivery

“…The unique magnetic properties of ion-containing inorganic nanoparticles make them highly efficient for imaging and diagnosis in cancer therapy [162]. Moreover, since ART-type drugs are considered radical precursors, ion-containing inorganic nanoparticles have attracted great attention for cancer nanotherapy [203]. Zhang et al developed visible light-sensitive iron oxide nanoparticles (IONPs): Hyaluronic Acid (HA)-TiO 2 -IONPs/ART (~40 nm size), which realized the co-delivery of ART and Fe 2+ .…”