Multifunctional Nanotheranostics Probe Based On Manganese Dioxide Nanomaterials

Surgery,radiotherapy and chemotherapy are common clinical treatments for cancer,but these treatments have some obvious shortcomings.For example,the treatment is incomplete,non-targeted,prone to drug resistance,reduces the body's immune ability,and has greater toxic and side effects.With the development of human's understanding of tumor,some novel tumor treatment methods are emerging,including optical therapy,gene therapy,and immunotherapy.These treatment methods are minimally invasive or non-invasive,highly selective,and have low toxic and side effects.They have become potential effective methods for cancer treatment.With the continuous development of nanotechnology in recent years,nanomaterials are showing their talents in the fields of biology,medical engineering and pharmacy,especially in the diagnosis and treatment of tumors.Applying the interaction between photons and nanomaterials to the exploration of life science is a great progress of human beings.By controlling the synthesis of biocompatible nano-biomaterials and their derivatives,it can be used to achieve a variety of different active or passive photonics functions.When the light of appropriate frequency radiates to the tumor site where a large number of nanomaterials or drug molecules are enriched,the nanomaterials or drug molecules will absorb energy and jump to different electronic excited states,and various phenomena such as light,sound and heat will appear in the form of radiation or non-radiation transitions,which can be applied to the diagnosis and treatment of tissues.With the development of cross integration of life science and optical technology,optical imaging as an important means of biological imaging,including X-ray,?-ray,fluorescence imaging,photoacoustic imaging,Raman spectroscopy,etc.,has attracted the common attention of researchers.In recent years,fluorescence imaging technology is widely used in the field of biological imaging.It is also used to distinguish normal tissue and pathological tissue to guide surgery.In the near-infrared II window?NIR-II,1000-1700 nm?range,the spontaneous fluorescence,absorption and scattering of photons in biological tissues are small,so the NIR-II fluorescent dye has higher signal-to-noise ratio and stronger tissue penetration depth.Photoacoustic imaging is a new biological imaging technology with optical absorption and ultrasonic as information carrier.The imaging technology integrates the advantages of optical imaging and ultrasonic imaging,has the characteristics of high contrast and large penetration depth,and has a huge development prospect in the field of imaging.Photothermal therapy?PTT?and Photodynamic therapy?PDT?as new efficient tumor optical therapy,has attracted extensive attention of researchers.However,there are some limitations in optical therapy.For example,the absorption and scattering of near-infrared light by tissue leads to the insufficient penetration depth of light;The tumor is vigorously metabolized,the oxygen consumption is large,the blood vessel wall is fragile and unevenly distributed,resulting in a wide range of hypoxic areas in the tumor microenvironment;Clinical research shows that there is an irreparable defect in a single treatment method,and the treatment of tumors is incomplete.In response to the above problems,the main research contents of this thesis are as follows:1.A nanomaterial based on Au/Ag-Mn O₂-Ce6?AAM-Ce6 HNSs?was constructed,which has both tumor diagnosis and treatment functions,It has extensive absorption in the near-infrared biological window,and has significant light-heat conversion capability in the NIR-II.At the same time,the Mn O₂ nanoparticles can catalyze the decomposition of endogenous H₂O₂ to produce O₂and Mn²⁺ions in the acidic tumor microenvironment,which not only enhances the therapeutic effect of PDT,but also can be used as a contrast agent for magnetic resonance imaging?MRI?.In conclusion,the AAM-Ce6 HNSs can be used for PTT/PDT combination therapy guided by fluorescence,photoacoustic,magnetic resonance trimodal imaging.The experimental results show that the multifunctional PTT/PDT combination therapy shows a better therapeutic effect than any monotherapy.2.Bovine serum albumin-manganese dioxide nanoparticles?BSA-Mn O₂?were synthesized by biomineralization,which has good stability and biocompatibility.Diketopyrrolopyrrole?DPP-BT?a NIR-II fluorescent dye was loaded into the hydrophobic cavity of albumin through hydrophobic interaction.A multi-functional nanodiagnosis and treatment platform?DPP-BT@BSA-Mn O₂?with PTT/PDT combined therapy guided by fluorescence,photoacoustic and magnetic resonance trimodal imaging was obtained.Under the irradiation of a single NIR laser?730 nm?,DPP-BT@BSA-Mn O₂ can produce NIR-II fluorescence signal and photoacoustics signal,has excellent PTT and PDT performance.The Mn O₂ nanoparticles catalyze the decomposition of H₂O₂in the acidic tumor microenvironment to produce O₂ and Mn²⁺ions.While improving the local hypoxia characteristics of the tumor microenvironment,Mn²⁺ions are introduced as contrast agents for MRI.This multi-functional nano-platform with multiple imaging and treatment methods triggered by the tumor microenvironment and a single NIR light is expected to be applied to the clinical diagnosis and treatment of tumors in the future.