Activatable Mitochondria‐Targeting Organoarsenic Prodrugs for Bioenergetic Cancer Therapy

Abstract

Despite widespread applications for cancer treatment, chemotherapyisrestricted by several limitations,including low targeting specificity,a cquired drug resistance,a nd concomitant adverse side effects.I tr emains challenging to overcome these drawbacks. Herein, we report an ew bioenergetic approach for treating cancer efficiently.Asaproof-ofconcept, we construct activatable mitochondria-targeting organoarsenic prodrugs from organoarsenic compounds and traditional chemotherapeutics.T hese prodrugs could accomplish selective delivery and controlled release of both therapeutic agents to mitochondria, which synergistically promote mitochondrial ROS production and induce mitochondrial DNA damage,finally leading to mitochondria-mediated apoptosis of cancer cells.O ur in vitro and in vivo experiments reveal the excellent anticancer efficacy of these prodrugs,u nderscoring the encouraging outlook of this strategy for effective cancer therapy.

Metformin attenuates H2O2‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

“…Under physiological conditions, ROS are produced in the mitochondria and are partially eliminated by antioxidants, such as SOD and CAT, to maintain a dynamic balance. When excessive amounts of free radicals are produced and the antioxidant function is decreased, the ability of the body to eliminate and self-repair may be exceeded; therefore, the release of copious quantities of free radicals induces apoptosis ( 32 ). Thus, H 2 O 2 was used in the present study to mimic the hyperoxidative state in postmenopausal osteoporosis and induce osteoblast apoptosis.…”

Nanoparticulation of Prodrug into Medicines for Cancer Therapy

“…Drugs with tolerant side effects attract in particular the attentions of medicinal chemists since it is that these imperfect ones serve as a decent starting point for further modifications/improvements since de novo design is more timeconsuming and challenging. Recently, some unusual prodrugs have been newly developed, such as organoarsenic [248] and antimony prodrugs, [249] which enriched our arsenal to combat with hazardous diseases, including malignant cancer. www.advancedsciencenews.com www.advancedscience.com Nanomedicine, fuled by nanotechnology, manipulates therapeutical materials in nanoscale and promises scientific even clinic advancement in disease treatment.…”

Mitochondria-Targeted Nanocarriers Promote Highly Efficient Cancer Therapy: A Review

“…Under the help of the TPP-targeting group, prodrugs can accumulate in the mitochondria selectively. The prodrugs were able to release trivalent organoarsenicals and chemotherapeutics upon reduction, leading to mitochondriamediated apoptosis in cancer (Luo et al, 2021). Han et al (2015) established a self-delivery system PpIX-PEG-(KLAKLAK) 2 which was designated as PPK.…”