Recent Progress of Alkyl Radicals Generation‐Based Agents for Biomedical Applications

Abstract

Photodynamic therapy (PDT) is extensively explored for anticancer and antibacterial applications. It typically relies on oxygen-dependent generation of reactive oxygen species (ROS) to realize its killing effect. This type of therapy modality shows compromised therapeutic results for treating hypoxic tumors or bacteria-infected wounds. Recently, alkyl radicals attracted much attention as they can be generated from some azo-based initiators only under mild heat stimulus without oxygen participation. Many nanocarriers or hydrogel systems have been developed to load and deliver these radical initiators to lesion sites for theranostics. These systems show good anticancer or antimicrobial effect in hypoxic environment and some of them possess specific imaging abilities providing precise guidance for treatment. This review summarizes the developed materials that aim at treating hypoxic cancer and bacteria-infected wound by using this kind of oxygen-irrelevant alkyl radicals. Based on the carrier components, these agents are divided into three groups: inorganic, organic, as well as inorganic and organic hybrid carrier-based therapeutic systems. The construction of these agents and their specific advantages in biomedical field are highlighted. Finally, the existing problems and future promising development directions are discussed.

Carbon Dots in Bioimaging, Biosensing and Therapeutics: A Comprehensive Review

“…Therefore, the production of ROS is a further strategy for achieving potent antibacterial effects. [224][225][226] Qu et al developed CDs with the catalase-like activity, capable of catalyzing the decomposition of H 2 O 2 to produce •OH. Taking advantages of the potent antibacterial activity of •OH, the toxicity of H 2 O 2 at high levels towards normal cells in the wound could be avoided (Figure 7c).…”

Dual-responsive and NIR-driven free radical nanoamplifier with glutathione depletion for enhanced tumor-specific photothermal/thermodynamic/chemodynamic synergistic Therapy

“…However, the leaked AIPH during circulation may slowly decompose at physiological temperature, causing undesired off-target toxicity to normal cells. 27,28 In addition, the upregulated glutathione (GSH) in cancer cells has a potent scavenging effect on the generated free radicals, thereby dramatically diminishing the therapeutic efficiency of TDT. [29][30][31] Thus, designing a tumor-specific nanoreactor with the ability of controlled drug release and GSH depletion is of great importance to realize safe and efficient TDT.…”

Zirconia‐Platinum Nanohybrids for Ultrasound‐Activated Sonodynamic‐Thermodynamic Bimodal Therapy by Inducing Intense Intracellular Oxidative Stress

“…[ 18 ] On the other hand, as another category of cytotoxic ROS, alkyl radicals generated from thermally decomposable azo initiators can also elevate oxidative stress to induce tumor cell death, and this process is irrelevant with the oxygen saturation level. [ 19–21 ] The azo salt of 2,2′‐azobis[2‐(2‐imidazolin‐2‐yl)propane] dihydrochloride (AIPH), deemed to be a heat‐liable alkyl radical generator, can be instantly disintegrated under thermal stimulation. The decomposition products have been demonstrated to consume glutathione and cause oxidative damage toward cytoskeleton and organelles, which eventually induces lethal redox dyshomeostasis.…”