Abstract
This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the prostate cancer cells. The prostate cancer targeting was mediated by the AntiSar antibodies decorated surface of the nanocage. Formation of the chitosan nanoparticles was determined using a ninhydrin assay and differential pulse voltammetry. Obtained results showed the strong effect of tripolyphosphine on the nanoparticle formation. The zinc ions affected strong chitosan backbone coiling both in inner and outer chitosan nanoparticle structure. Zinc electrochemical signal depended on the level of the complex formation and the potential shift from −960 to −950 mV. Formed complex is suitable for doxorubicin delivery. It was observed the 20% entrapment efficiency of doxorubicin and strong dependence of drug release after 120 min in the blood environment. The functionality of the designed nanotransporter was proven. The purposed determination showed linear dependence in the concentration range of Anti-sarcosine IgG labeled gold nanoparticles from 0 to 1000 µg/mL and the regression equation was found to be y = 3.8x − 66.7 and R2 = 0.99. Performed ELISA confirmed the ability of Anti-sarcosine IgG labeled chitosan nanoparticles with loaded doxorubicin to bind to the sarcosine molecule. Observed hemolytic activity of the nanotransporter was 40%. Inhibition activity of our proposed nanotransporter was evaluated to be 0% on the experimental model of S. cerevisiae. Anti-sarcosine IgG labeled chitosan nanoparticles, with loaded doxorubicin stabilized by Zn ions, are a perspective type of nanocarrier for targeted drug therapy managed by specific interaction with sarcosine and metallothionein for prostate cancer.
Highlights
The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential in several cancer diseases
Given values are recalculated as 100 percent absorbance of CS-ninhydrin product without Dox. Obtained data of both signals show the variability from 5 to 10%. These results indicate the formed complex is stable and the doxorubicin has no effect on Zn/CS NPs stabilization
After CS NPs formation, the hemolytic activity decreased by 30% (Figure 8A). This effect was similar in the case of Zn/CS NPs‐AuMNPs and AntiSar/Zn/CS NPs‐AuMNPs 40% respectively 41%. These results suggested rather that tripolyphosphate penta basic (TPP) addition the formation of zinc stabilized NPs leads to decrease CS toxicity and hemolytic activity
Summary
The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential in several cancer diseases. One of the most utilized biopolymer is chitosan (CS) due to its beneficial chemical-physical properties [1]. Previous studies reported its antioxidant [2], anti-hypertensive [3], anti-diabetic, anti-obesity [4], neuroprotective [5] and bacteriostatic effects [6]. Chitosan plays an important role in the cell regulation and tissue regeneration [7,8]. From the chemical point of view, chitosan is a weak base polysaccharide with high amino-group density per disaccharide unit. In the dependence on pH of environment the amino groups ensure diverse molecular behavior. Acidic pH causes protonation of amino-groups and positive charge. The chitosan solubility increases when decreasing the value of pH [9]
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