Biodegradable hollow mesoporous organosilica nanotheranostics  (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer

Abstract

Background: CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells’ apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells’ mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd).Results: HMON@CuS/Gd exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/ IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo. Conclusion: HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.

Self-Amplification of Oxidative Stress with Tumor Microenvironment-Activatable Iron-Doped Nanoplatform for Targeting Hepatocellular Carcinoma Synergistic Cascade Therapy and Diagnosis

“…1a and b). In brief, the core/shell structure of thioether hybrid mesoporous silica nanoparticles (HMON NPs) was constructed based on the chemical homology principle through the co-hydrolysis and co-condensation of bis [3-(triethoxysilyl)propyl]tetrasul de (BTES) and tetraethoxysilane by cetyltrimethylammonium chloride (CTAC) as the structural-directing and pore-forming agent, triethanolamine (TEA) as the alkaline catalyst and tetraethyl orthosilicate (TEOS) as the silica precursor [35,42]. The disul de-bridged HMON NPs obtained by using mild ammonia instead of strong HF/NaOH as the etching agent because of the Si-C bonds within the shell are more stable and stronger than the Si-O bonds within the core [43].…”

“…The thioether hybrid HMON NPs were selected for biomedical applications due to their reductive responsive biodegradability due to in-frame disul de bond cleavage triggered by GSH [44]. Interestingly, the coordination of iron and protein would make the silica framework rich in reaction sites and further accelerated the biodegradation of the silica framework [45].…”

“…The construction of organic/inorganic hybrid material nanoplatform is expected to combine the advantages of both and overcome their respective shortcomings, thus showing broad prospects for clinical applications [34]. To satisfy the above multifaceted requirements, biocompatible and biodegradable hollow mesoporous organosilica nanoparticles (HMON NPs) have been successfully constructed via selective introduction of bis [3-(triethoxysilyl)propyl]tetrasul de (BTES) [35]. The thioether-hybridized HMON NPs are chosen for e cient delivery of DOX owing to their GSHresponsive biodegradability and controlled release of anti-tumor drugs.…”

Self-amplification of Oxidative Stress With Tumour Microenvironment-activatable Iron-doped Nanoplatform for Targeting Hepatocellular Carcinoma Synergistic Cascade Therapy and Diagnosis

“…The thioether hybrid HMON NPs were selected for biomedical applications due to their reductive responsive biodegradability due to in-frame disul de bond cleavage triggered by GSH [44]. Interestingly, the coordination of iron and protein would enrich the silica framework with reaction sites and further accelerated the biodegradation of the silica framework [45].…”

“…The construction of organic/inorganic hybrid material nanoplatform is expected to combine the advantages of both and overcome their respective shortcomings, thus showing broad prospects for clinical applications [34]. To ful l the above multiple requirements, hollow mesoporous organosilica nanoparticles (HMON NPs) with biocompatible and biodegradable have been correctly developed with the aid of selective introduction of bis [3-(triethoxysilyl)propyl]tetrasul de (BTES) [35]. GSH-responsive biodegradability and controlled release of anti-tumour drugs of the thioetherhybridized HMON NPs that e cient delivery of DOX.…”