A Robust Oxygen-Carrying Hemoglobin-Based Natural Sonosensitizer for Sonodynamic Cancer Therapy

Abstract

The development of novel sonosensitizers with outstanding reactive oxygen (ROS) generation capacity and great biocompatibility poses a significant challenge for the clinical practice of sonodynamic therapy (SDT). In this work, hemoglobin (Hb) with natural metalloporphyrin was first shown to possess great potential as a sonosensitizer. Compared with traditional organic sonosensitizers, Hb had satisfactory sono-sensitizing efficiency because four the porphyrin molecules were separated by four polypeptide chains. This effectively avoided the problem of low ROS quantum yield caused by the stacking of hydrophobic porphyrins. Meanwhile, Hb is an efficient and safe oxygen carrier that may release O2 at hypoxic tumors site, which improved tumor oxygenation and subsequently enhanced SDT efficacy. Therefore, Hb was integrated with zeolitic imidazolate framework 8 (ZIF-8) to form a nanoplatform that demonstrated a potent suppression effect on deep-seated tumors under ultrasound irradiation.

Metal–Organic Framework Nanoparticles Power DNAzyme Logic Circuits for Aberrant MicroRNA Imaging

“…Recently, metal–organic frameworks (MOF NPs) have attracted great attention in selective catalysis, gas storage and separation, − and drug delivery − owing to their large surface area, high and tunable porosity, and good functionalization . In particular, zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs), a subclass of MOF NPs, have been utilized as a smart nanocarrier for accommodating functional nucleic acids containing siRNA, CpG, and DNAzyme by electrostatic interactions. − Moreover, the nanoscale ZIF-8 NPs can be delivered into cells via the endocytosis pathway and then decomposed under acidic conditions of endo-lysosomes to motivate the controlled cargo release. − Recent studies have found that Cu 2+ -doped ZIF-8 NPs (Cu/ZIF-8 NPs) not only maintain the unique properties of ZIF-8 NPs but also supplement an adequate amount of DNAzyme cofactor to implement the biocatalytic operation of the Cu 2+ -dependent DNAzyme in living cells. , Thus, the Cu/ZIF-8 NP-based nanoplatform could be employed as a versatile self-driven nanocarrier for the efficient delivery of DNAzyme logic circuits into cells.…”

Precision therapy through breaking the intracellular redox balance with an MOF-based hydrogel intelligent nanobot for enhancing ferroptosis and activating immunotherapy

“…13 Consequently, achieving both effects of GSH depletion and improving ROS augmentation simultaneously to break the redox balance is a hopeful tactic in the special tumor microenvironments of high ROS and GSH concentrations. 14,15 Most inorganic catalysts exhibit anti-cancer activity via braking the intracellular redox balance, for instance, Fe-based or Mn-based nanoenzymes. 16,17 Based on the morphology controllability and high cytotoxic hydroxyl radical generation, inorganic catalysts have paved the way for potential biomedical and therapeutic engineering applications.…”

Regulating Acidosis and Relieving Hypoxia by Platelet Membrane-Coated Nanoparticle for Enhancing Tumor Chemotherapy

“…Even worse, this process will exacerbate tumor hypoxia, which undermines the therapeutic effect. Hence, hemoglobin (Hb) is introduced as a carrier to load oxygen, which could relieve hypoxia and increase lactic acid conversion efficiency in cancer therapy ( Welter et al, 2016 ; Otsuka et al, 2018 ; Yang et al, 2018 ; Yuan et al, 2021 ). On this basis, acidosis and hypoxia of the tumor microenvironment could be alleviated; meanwhile, the multidrug resistance (MDR) of the tumor will be diminished.…”