Cobalt-doped Hollow Polydopamine For Doxorubicin And Berberine Delivery And Antitumor Research

Chemotherapy is currently the most common therapeutic approach used for cancer treatment in the clinic.A variety of natural chemical compounds derived from plants have been shown to have excellent anti-cancer effects in both in vitro and in vivo experiments,but poor water solubility,rapid metabolism in vivo,and inability to accumulate effectively in focal sites have limited the use of most natural compounds in clinical cancer treatment.Advances in nanotechnology have effectively driven the use of nanomaterials as drug carriers for drug delivery.The use of nano-drug carriers for drug delivery not only improves the bioavailability of drugs,but also reduces the toxic side effects of drugs,and a variety of nano-drug carriers can themselves mediate multiple therapeutic modalities,which can have a synergistic effect with the delivered drugs.However,classical nano-drug carriers such as liposomes and micelles have low drug loading capacity and potential risk of hepatotoxicity and allergic reactions.Therefore,the design and development of new multifunctional biodegradable nano-drug carriers for efficient drug delivery to achieve efficient cancer treatment is an urgent issue.Polydopamine（PDA）is a melanin-like polymer formed by the polymerization of a catecholamine neurotransmitter in the brain,which has been widely used in biomedical applications due to its high biosafety and compatibility.PDA has a certain absorption in the near infrared region which allows it applied for photothermal therapy（PTT）and photoacoustic Imaging（PAI）.In this work,a hollow polydopamine nanostructure（Co HPDA）containing traces of cobalt was prepared using Chelation Competition Induced Polymerization（CCIP）.The nanostructures were used to study the effectiveness of the nanocarriers in improving the bioavailability of the natural compounds for anti-tumour therapy,followed by the selection of the water-soluble chemotherapeutic drug Doxorubicin（DOX）and the hydrophobic natural compound Berberine（BBR）as target drugs.Transmission electron microscopy and scanning electron microscopy showed that the average particle size of Co HPDA was 168.11±23.65 nm,with a hollow rhombic orth dodecahedral structure;the results of nitrogen adsorption and desorption tests showed that the relative specific surface area of Co HPDA was 43.051 m2-g-1;the results of X-ray photoelectron spectroscopy showed that Co HPDA consisted of four elements,C,N,O and Co.The results of X-ray photoelectron spectroscopy show that Co HPDA is composed of four elements:C,N,O and Co.The Co element in Co HPDA is mainly in the form of Co²⁺and Co³⁺by calculation fitting analysis.The results of the photothermal performance experiments showed that Co HPDA has a concentration-dependent and power-dependent warming effect,and maintains good photothermal stability after repeated irradiation,with a photothermal conversion efficiency of 28%.In addition,the prepared Co HPDA exhibited obvious functions to interfere with the internal environment of tumor cells,such as the consumption of Glutathione（GSH）and production of O₂by catalyze H₂O₂in the simulated tumor microenvironment.In terms of drug loading,DOX can be loaded onto Co HPDA nanocarriers by adjusting the drug ratio,and the drug loading and encapsulation efficiency can reach 55.09±1.09%and 61.39±2.68%,respectively.Fourier transform infrared（FTIR）and ultraviolet visible（UV-Vis）spectroscopy showed the characteristic absorption peaks of DOX,which could determine the successful loading of the drug.The drug release experiments showed that Co HPDA@DOX-HA is a drug delivery system with both tumor microenvironment and photothermal response to stimulated release.The results of in vitro anti-tumor experiments showed that Co HPDA@DOX-HA had a good anti-tumor effect and the final cell survival rate in the photothermal combination chemotherapy treatment group was only 16.64±5.68%.BBR was loaded according to the DOX loading method.The drug loading and encapsulation rate was 68.07±0.038%and 85.29±0.15%,respectively.In vitro anti-tumor MTT results showed that the survival rate of 4T1 cancer cells treated with Co HPDA@BBR combined with photothermal therapy was only 3.08±2.5%compared with equivalent BBR.In this thesis,a hollow polydopamine nanocarrier with rhombic orth dodecahedron containing traces of cobalt was synthesized and its application in drug delivery was verified by loading DOX and BBR.The prepared Co HPDA can deplete GSH in the tumor microenvironment and react with hydrogen peroxide to produce O₂,which can interfere with the redox balance in the tumor cells and alleviate the tumor cells’hypoxic state,and improve the sensitivity of the tumor cells to drugs.The PTT and PAI functions of the nano-drug carriers can realize the combined PTT/chemotherapy treatment,and the PAI can track the therapeutic effect to achieve precise treatment.The nano-drug delivery carriers prepared in this thesis exhibit highly efficient drug delivery and adjuvant therapeutic effects,providing a new method and a new way to improve the anti-tumour effects of natural compounds.