Theranostic Applications Of Multifariously Fabricated Magnetic Nanobiomaterials In Breast Cancer

Breast cancer is the most frequently diagnosed and one of the leading causes of death in female worldwide.Traditional therapy approaches such as radiotherapy,chemotherapy,and surgery have many drawbacks and cause collateral damages to healthy cells/tissues.Phototherapy approaches,such as photothermal therapy?PTT?and photodynamic therapy?PDT?are the most promising therapy approaches,which hold great promise to overcome the limitations of traditional treatment methods.Indeed,one of the major advantages of theranostic is the ability to incorporate multiple functionalities in an agent,which can be used for imaging and therapy.Magnetic nanoparticles/nanocomposites are of paramount importance due to their wide range of biomedical applications.In this PhD thesis,various types of magnetic nanoparticles-based biomaterials are fabricated and investigated their theranostic applications in breast cancer?MCF-7 cell line?.1)In the first part,a facile solvothermal method is used to fabricate the polyethylene glycol?PEG?coated Fe₃O₄ nanoflowers with controllable dimensions?70-250 nm?and their biomedical applications are investigated.The therapeutic performance of Fe₃O₄ nanoflowers?Fe-NFs?is evaluated and compared with commercially available black TiO₂?b-TiO₂?nanoparticles under 808 nm laser at 1.3 W cm^–2 for 5-min.The cell viabilities in Fe-NFs and b-TiO₂ incubated cells decrease in a concentration-dependent manner,20.5 percent and 18 percent cancer cells left viable at concentrations up to 200?g mL^–1 respectively.The photothermal therapy efficiency of Fe-NFs is observed to be better than the reported Fe₃O₄ nanoparticles?NPs?.In vivo results depict that after being exposed to 808 nm laser at 0.7 W cm^–2 for 5 min,the temperature of the tumor site reaches 52°C with Fe-NFs.Both in vitro and in vivo investigations demonstrate that the therapeutic performance of Fe-NFs is comparable to b-TiO₂.The Fe-NFs exhibit superparamagnetic behavior and excellent size-dependent saturation magnetization values?74-82 emu/g?.The relaxivity ratio?r₂/r₁?of small-sized Fe-NFs?70 nm?is 66.9,which suggests that the prepared nanoflowers are an excellent T₂-weighted MRI contrast agent.Therefore,Fe-NFs show enhanced magnetic resonance imaging capability to monitor therapeutic performance.2)In the second part of work,a versatile fabrication strategy is introduced to design a new theranostic nanocomposites?NCs?i-e.Fe₃O₄-black TiO₂ nanocomposites?Fe-Ti NCs?,with tunable diameter range?30-85 nm?.The Fe-Ti NCs exhibit an intense broad light absorption band?550–850 nm?,inherited phototherapy and MR-imaging properties.The results demonstrate that the temperature elevations of Fe-Ti NCs are better than individual NPs and the exhibited temperature change??T?at concentrations 50?g mL^–1 is 34-36°C.Owing to the its enhanced absorbance at 671 nm,the change in temperature under 671 nm laser(1 W cm^-2)is comparable to 808 nm laser(1.3 W cm^-2).Thus,the Fe-Ti NCs primarily hold an enhanced dual-wavelength photothermal conversion capacity.The cell viabilities significantly decrease at 0.5-0.7 W cm^–2 and left negligible living cells when laser intensity reaches 1-1.3 W cm^–2.The confocal microscopy analysis demonstrates reactive oxygen species?ROS?-mediated synergistic phototherapy?PTT/PDT?capability at low concentration and power density.In vivo photoinduced tumor ablation capability is also assessed and monitored the rapid increase in temperature?60±2°C?after being exposed to 808 nm laser at 0.7 W cm^–2 for 5 min.Then,the same change in temperature is observed under 671 nm laser at 0.5 W cm^–2.Thus,in vitro and in vivo dual-wavelength laser tumor ablation ability of Fe-Ti NCs verified excellent synergistic phototherapy efficacy against tumors.The tumors reappear after in vivo treatment with Fe-NFs/b-TiO₂ nanoparticles,which is a disadvantage of incomplete thermal therapy while treatments with Fe-Ti NCs result in complete tumor ablation.Moreover,Fe-Ti NCs exhibit superparamagnetic behavior,high magnetization value(48 emug^-1),good r₂ relaxivity value(38.2 mM^-1 s^-1),and excellent T₂ imaging capability to monitor therapeutic performance.3)In the third part of the work,we introduce a facile method to dope magnetic nanobiomateirals for enhanced T₁ imaging and phototherapy applications.We have developed a doping method using b-TiO₂ NPs.The fabrication of doped materials,such as Mn₃O₄?MnO?,Fe-doped Mn₃O₄,(Mn_1-x-x Fe_xO),b-TiO₂ containing Fe-doped Mn₃O₄(Mn_1-x-x Fe_xO-b-TiO₂)and b-TiO₂ NPs containing Mn-doped ZnO(Zn_1-x-x Mn_xO-b-TiO₂)are carried out by the modified solvothermal method as developed in our previous work.Moreover,doped-nanoparticles are found to be an excellent T₁-weighted contrast agent.Finally,this work highlights the huge potential of magnetically-doped nanoparticles in theranostics applications for T₁-weighted imaging-guided cancer therapy.