Abstract:Electrodynamic therapy (EDT) and chemodynamic therapy (CDT) have the potential for future tumor treatment; however, their underlying applications are greatly hindered owing to their inherent drawbacks. The combination of EDT and CDT has been considered to be an effective way to maximize the superiorities of these two ROS-based methodologies. However, the development of novel nanomaterials with "one-for-all" functions still remains a big challenge. In this work, the polyoxometalate nanoparticles (NPs) were deco… Show more
“…Most of the POVs are often negatively charged, and these metal-based drugs undergo various chemical changes in biological fluids due to their speciation chemistry. [25,28] Hence, the physiological stability of POVs is critically important for their biomedical application. To evaluate the in vitro stability of the POVs, the UV-vis absorbance of POVs was recorded (Figure 2A-E and Figures S9-S14, Supporting Information) after incubation of POVs in water, phosphate-buffered saline (PBS) of different pH, and PBS containing 10% fetal bovine serum (FBS) at 37 °C for 24 h. The UV-vis absorbance spectra of POVs show little changes in the absorption intensities and peaks, suggesting that the tested POVs were fairly stable under these conditions including acidic conditions (in PBS at pH4).…”
Section: Integrity and Fate Of Povs Under The Experimental Conditionsmentioning
The therapeutic application of vanadium compounds is plagued by their poor bioavailability and potential adverse effects. Herein, 1 nm polyoxovanadate (POV) clusters are functionalized with alkyl chains of various lengths and studied for the effect of surface engineering on their preclinical pharmacokinetics and typical insulin‐sensitizing activity. The concentrations of surface engineered POVs in plasma, urine, and feces are monitored after a single administration to rats. The POVs exhibit a two‐compartment profile of in vivo kinetics, and the surface engineering effect plays an important role in renal clearance of the POVs comparable to small molecules. POVs functionalized with long alkyl chains show much shorter elimination half time t1/2β and higher elimination fractions (50%) within 48 h than pristine POVs, suggesting favorable elimination kinetics to mitigate the possible side effects of vanadium. Meanwhile, long alkyl chain modification leads to a 76% increment of oral bioavailability in contrast to unmodified POVs. As suggested by glucose tolerance tests and sub‐chronic toxicity tests, the above two factors contribute to the enhanced therapeutic efficacy of POVs while mitigating their adverse effects. The surface engineering protocol provides a feasible approach to the optimization of the bioavailability and pharmacokinetic properties of POVs for promoted insulin‐sensitizing activities.
“…Most of the POVs are often negatively charged, and these metal-based drugs undergo various chemical changes in biological fluids due to their speciation chemistry. [25,28] Hence, the physiological stability of POVs is critically important for their biomedical application. To evaluate the in vitro stability of the POVs, the UV-vis absorbance of POVs was recorded (Figure 2A-E and Figures S9-S14, Supporting Information) after incubation of POVs in water, phosphate-buffered saline (PBS) of different pH, and PBS containing 10% fetal bovine serum (FBS) at 37 °C for 24 h. The UV-vis absorbance spectra of POVs show little changes in the absorption intensities and peaks, suggesting that the tested POVs were fairly stable under these conditions including acidic conditions (in PBS at pH4).…”
Section: Integrity and Fate Of Povs Under The Experimental Conditionsmentioning
The therapeutic application of vanadium compounds is plagued by their poor bioavailability and potential adverse effects. Herein, 1 nm polyoxovanadate (POV) clusters are functionalized with alkyl chains of various lengths and studied for the effect of surface engineering on their preclinical pharmacokinetics and typical insulin‐sensitizing activity. The concentrations of surface engineered POVs in plasma, urine, and feces are monitored after a single administration to rats. The POVs exhibit a two‐compartment profile of in vivo kinetics, and the surface engineering effect plays an important role in renal clearance of the POVs comparable to small molecules. POVs functionalized with long alkyl chains show much shorter elimination half time t1/2β and higher elimination fractions (50%) within 48 h than pristine POVs, suggesting favorable elimination kinetics to mitigate the possible side effects of vanadium. Meanwhile, long alkyl chain modification leads to a 76% increment of oral bioavailability in contrast to unmodified POVs. As suggested by glucose tolerance tests and sub‐chronic toxicity tests, the above two factors contribute to the enhanced therapeutic efficacy of POVs while mitigating their adverse effects. The surface engineering protocol provides a feasible approach to the optimization of the bioavailability and pharmacokinetic properties of POVs for promoted insulin‐sensitizing activities.
“…Electric field can not only remotely control drug release but can also trigger chemical reaction to produce reactive oxygen species (ROS) for electrodynamic therapy (EDT). 48–49 The electric field could drive catalytic reaction on nanoparticle catalysts to produce ROS to promote apoptosis following the mechanism of electrodynamic therapy. 50 Figure 7.(a) Photographs of 4T1 tumor-bearing mice and their histological images of H&E, TUNEL, and antigen Ki-67 immunofluorescence stained tumor tissue sections after 15 days of different treatments.…”
Section: Resultsmentioning
confidence: 99%
“…Electric field can not only remotely control drug release but can also trigger chemical reaction to produce reactive oxygen species (ROS) for electrodynamic therapy (EDT). [48][49] The electric field could drive catalytic reaction on nanoparticle catalysts to produce ROS to promote apoptosis following the mechanism of electrodynamic therapy. 50…”
Section: In Vivo Ef-stimulation Of Eftdds For Efficient Chemotherapymentioning
Precision therapy has developed as an important strategy for cancer treatment. We have developed an external electric field (EF) controlled targeting drug delivery nanosystem (TDDS) for precision cancer therapy. The electric field responsive targeting drug delivery nanosystem (EFTDDS) is synthesized by functionalizing mesoporous silica with polynitrophenyl-methacrylamide-folate (PNMAFA). The functional molecules grafted in the mesopores effectively encapsulate the drugs in the EFTDDS and control the drug release by nitrylphenyl dipolar responding to electric field. The EFTDDS has achieved high electric field control as demonstrated by the promoted EF-responsive release and the low nonspecific leakage of the doxorubicin. Furthermore, when breast cancer xenograft models on nude mice were treated with EF-stimulated nanomedicine, the tumor-inhibition rate increases to 75%, which is 2.7 times as high as that without electric field stimulation. The EFTDDS is demonstrated biodegradable, biocompatible, and EF remotely controllable, represents excellent inhibiting effect on tumor in vivo, and might become a promising nanomedicine platform for electrodynamic therapy (EDT) in the potential clinical applications.
“…Additionally, some materials with anionic polyelectrolytes have also been used to prepare pH-sensitive nanocarriers for drug delivery [ 215 ]. However, the strategy of taking advantage of anionic amphiphilic molecules to prepare pH-responsive and tumor-targeted nanocarriers can be different from that utilizing cationic materials.…”
Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.
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