Available as a pre-proof in the journal Acta Biomaterialia, scientists have developed reactive oxygen species (ROS)-activated nanoscale coordination polymers (NCPs) that can be used for ultrasound-mediated therapy for cancer treatment.
Study: ROS-Activated Nanoscale Coordination Polymers for Enhanced Ultrasound-mediated Therapy for the Treatment of Cancer. Image Credit: Tyler Olson/Shutterstock.com
ROS-based Cancer Therapies
Many reactive oxygen species (ROS)-containing ions or free radicals are available that cause cytotoxicity in cancer cells without causing non-specific damage to cellular components.
Scientists have been successful in developing various ROS-based cancer therapies, including chemodynamic therapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), and radiodynamic therapy (RDT). Compared to all other treatments, SDT has been reported to have the maximum tissue-penetrating capacity and can induce apoptosis in the deep tumor tissue.
Importantly, it exhibits good biological safety, as it does not impose toxicity of metal ions or radiation. Typically, SDT depends on the interaction between ultrasound (US) and sonosensitizers to produce ROS for anti-tumor therapy with greater accuracy and minimum side effects.
Scientists have emphasized that to enhance the therapeutic efficacy of SDT, it is important to develop novel sonosensitizers with high catalytic activities.
Previous studies have indicated that porphyrins and their derivatives could be important sonosensitizers due to their large π- conjugated aromatic structures.
These compounds revealed a robust absorption band with a high yield of singlet oxygen quantum in the visible region. However, as porphyrins, and their derivatives, exhibit solid hydrophobic interactions and π−π stacking, it easily aggregates under US irradiation.
The contact of porphyrin with light and oxygen molecules is significantly reduced, decreasing the generation efficiency of ROS dramatically. Scientists have continually worked to overcome the aforementioned shortcomings and develop novel porphyrins and derivatives based on nanoparticles, which possess greater stability and improved ROS generation.
A study has recently reported the development of novel sonosensitizers, i.e., porphyrins-based nanoscale coordination polymers (NCPs) that serve as a coordination network between porphyrins ligands and metal ions, to produce cytotoxic ROS, used in cancer therapy.
Previous studies have revealed that stimuli-responsive nanoplatforms can release drugs in a controlled manner. For example, SDT controlled via a thermal parameter can enhance the release rate of Doxorubicin (Dox), which is an effective US-induced therapy and chemotherapy for cancers.
Development of PTK@PEG/Dox Nanoplatforms - A New Treatment
In this new study, scientists developed ROS-sensitive NCPs (PTK) using porphyrins (PP) as organic polydentate ligands. Additionally, they used platinum (Pt) as center ions, and thioketals (TK) linkers at ROS-sensitive sites via a simple one-pot hydrothermal method.
Scientists used scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to determine the morphology and size of the as-prepared PTK.
PTK showed a uniform layer owing to the π-π interaction between molecules and the size of the layer was measured to be 100 nm. The US-triggered ROS generation efficiency of PTK@PEG was determined using the 1,3-diphenylisobenzofuran (DPBF) degradation experiments, which revealed promising US-mediated ROS production ability of PTK@PEG.
Researchers took advantage of the highly porous PTK nanostructure for drug delivery. They modified PEG2000 and Arg-Gly-Asp (RGD) to the PTK@PEG/Dox nanoplatforms that enhanced water solubility and fabricated the uptake efficiency of RGD/PTK@PEG/Dox.
The authors stated that Dox was effectively loaded (58.47%) on PTK through π-π conjugation of PP and fluorene groups in TK linkers (PTK@PEG/Dox). They revealed that the absorption values augmented along with the increase of US irradiation time.
This study reported that when the duration of US irradiation was increased to 75 minutes, the release rate of Dox from PTK@PEG/Dox reached stability without any further release.
Researchers estimated the release efficiency of Dox from PTK@PEG/Dox to be around 62.05%, whereas the release rate without US irradiation was only 11.13%. This result implied that the US irradiation could improve the release efficiency of Dox from PTK@PEG/Dox nanoplatforms, significantly.
Researchers reported that the PEG shell had no negative effects on the release performance of Dox.
In vitro experiments demonstrated that PTK@PEG displayed a US-triggered thermal property, which was responsible for the generation of abundant ROS.
Scientists reported that when the PTK@PEG/Dox was internalized by MCF-7 cells, the nanoplatform could produce a high level of cytotoxic ROS under US irradiation. Unsurprisingly, the newly generated ROS could trigger apoptosis, initiate the cleavage of TK linkers, and cause an efficient release of Dox.
Conclusion
In this study, researchers constructed a ROS-sensitive sonosensitizer that could produce heating as well as a high concentration of ROS under US irradiation.
The newly developed PTK@PEG/Dox nanoplatforms demonstrated high anticancer effectiveness owing to the synergistic/enhanced US-mediated therapy and chemotherapy.
Researchers used MCF-7 cells as models to study the extraordinary penetration capacity of RGD/PTK@PEG/Dox and the release of Dox in the center of solid tumor tissue.
Reference
Zhao, J. et al. (2022) ROS-Activated Nanoscale Coordination Polymers for Enhanced Ultrasound-mediated Therapy for the Treatment of Cancer. Acta Biomaterialia. https://www.sciencedirect.com/science/article/pii/S1742706122001131?via%3Dihub
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