Biodegradable Nanoprodrugs: “Delivering” ROS to Cancer Cells for Molecular Dynamic Therapy

Abstract

Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next‐generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin‐modified MgO2 nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg2+. This reaction simultaneously produces abundant H2O2 to induce cell death and damage the structure of transferrin to release Fe3+, which will react with H2O2 to produce highly toxic ·OH to kill tumor cells.

Metal peroxides for cancer treatment

“…CO-520 is always used as a nonionic surfactant in reversed-phase microemulsion. There had a report to synthesize MgO 2 nanosheets [ 39 ]. Cyclohexane and CO-520 were added into MgCl 2 solution to create a microemulsion system.…”

“…Bu et al constructed transferrin-modified MgO 2 nanosheets (TMNSs), which have a corresponding response to the neutral acidity and low CAT activity of TME, MgO 2 reacts with H + to generate H 2 O 2 rapidly and damages the structure of transferrin on the surface of the nanosheets [ 39 ]. Then, transferrin releases the trapped Fe 3+ and generates cytotoxic ⋅ OH through the Fenton reaction.…”

Therapeutic Potential of Reactive Oxygen Species: State of the Art and Recent Advances

“…201 Alternative systems to increase drug selectivity and reduce side effects are under development. For instance, nanodrugs producing hydrogen peroxide and releasing Fe 3+ , to convert it into hydroxyl radicals 202 or Fe nanoparticles that simply accelerate endogenous hydrogen peroxide conversion into hydroxyl radicals via the Fenton reaction, 203 were developed. In particular, the latter decreased the in vitro viability of the HeLa cancer cell line to 22%, whereas it maintained the viability of the healthy cell line NIH-3T3 at levels higher than 80%.…”

Photoactivatable nanogenerators of reactive species for cancer therapy

“…It is a collective term including singlet oxygen ( 1 O 2 ), superoxide radical anion (O 2 ●- ), hydroxyl radical ( ● OH), hydrogen peroxide (H 2 O 2 ) [ 35 ]. ROS can destroy tumor cells through multifactorial mechanisms, including oxidizing the biological macromolecules, destroying angiogenesis to cut off the supply of nutrients to tumor cells [ 36 , 37 ]. Typically, five therapeutic strategies including radiation therapy [ [38] , [39] , [40] , [41] ], chemodynamic therapy [ [42] , [43] , [44] , [45] , [46] ], sonodynamic therapy [ [47] , [48] , [49] , [50] ], bioreductive chemotherapeutics (e.g., tirapazamine, TPZ) [ [51] , [52] , [53] , [54] ], and photodynamic therapy (PDT) [ [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] ] can generate ROS.…”