Abstract
Ultrasound (US)-triggered sonodynamic therapy (SDT) proves itself to be a formidable tool in the fight against cancer, due to its large spectrum of uses as a non-invasive therapeutic measure, while also demonstrating itself to be a certain improvement upon traditional SDT therapeutics. However, tumor hypoxia remains to be a major challenge for oxygen-dependent SDT. This study describes the development of an innovative, multi-use, catalyst-based and improved SDT targeting cancer, through the employment of a sonosensitizing curcumin (Cur) load embedded within a MnO2 core, together with an extraneous tumor cell membrane component. The latter allows for efficient tumor recognition properties. Hollowed-out MnO2 allows for efficient drug delivery, together with catalyzing oxygen generation from hydrogen peroxide present in tumor tissue, leading to enhanced SDT efficacy through the induction of a reduced hypoxic state within the tumor. In addition, Cur acts as a cytotoxic agent in its own right. The results deriving from in vivo studies revealed that such a biomimetic approach for drug-delivery actually led to a reduced hypoxic state within tumor tissue and a raised tumor-inhibitory effect within mouse models. Such a therapeutic measure attained a synergic SDT-based tumor sensitization treatment option, together with the potential use of such catalysis-based therapeutic formulations in other medical conditions having hypoxic states.
Highlights
Breast cancer remains a major cancer condition afflicting woman on a global scale, with present therapeutic measure still not providing full patient recoveries, in metastatic phases, which typically lead to a 90% mortality rate (Ho, 2020)
Bionic Catalyst for Cancer Therapy last 10 years have seen the research community focusing on light-mediated photodynamic therapy (PDT) (Zhang et al, 2016; Ren et al, 2020; Suo et al, 2020; Zhu Y. et al, 2020), where light-induced sensitizer elicitation leads to tumor cell apoptosis through the up-regulated secretion of reactive oxygen species (ROS), which are highly cytotoxic (Meng et al, 2019; Hu et al, 2020; Li S. et al, 2020)
The tumor cell membrane coated vesicle (CV) MC NPs has the appearance of a 5 nm-girth gray outer-shell when viewed under TEM (Figure 1A)
Summary
Breast cancer remains a major cancer condition afflicting woman on a global scale, with present therapeutic measure still not providing full patient recoveries, in metastatic phases, which typically lead to a 90% mortality rate (Ho, 2020). SDT is hindered from acting as a novel therapeutic option due to its reduced release of ROS in hypoxic states (Huang C. et al, 2020) In this respect, multiple research efforts focusing on angles such as enhanced direct-delivery of oxygen (O2) and hydro-photolysis are still limited in efficacy. A recent multi-use hollowed-out MnO2 nanocatalyst successfully served its objectives to reduce hypoxic states and as a drug-delivery system (Lyu et al, 2020) Once introduced, this nanocatalyst accumulates within the kidneys and is eventually cleared out as Mn2+ with minimal cytotoxicity effects (Zhao et al, 2014; Huang J. et al, 2020). The oxygen-burst was successful in redicing the hypoxic state within the tumor microenvironment and sensitized such tumor tissues to SDT measures Both in vitro and in vivo confirmed our novel CMC formulation provides a major therapeutic impact on tumor tissues with minimal adverse effects
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