Mitochondria play an important role in cell growth and survival, participate in many signal transduction processes, and provide power and energy for eukaryotic cells. On the other hand, mitochondrial dysfunction is closely related to diseases, such as neurodegenerative diseases and cardiovascular diseases. In recent years, due to the advantages of subcellular drug delivery in disease treatment, it has been widely concerned by scientists. Firstly, drug delivery to subcellular organelles can prevent the potential side effects of drug on other subcellular organelles; secondly, some drugs only affect the mitochondria and other subcellular organelles, so drug delivery to subcellular organelles can increase its bioavailability, allow the application of low-dose drugs and maximize the treatment index. At present, more and more nano biotechnology has been applied to the delivery of subcellular drugs, which promotes the rapid development of this field. In recent years, Professor Yao Shao Q. of National University of Singapore and Professor Li Lin of Advanced Materials Research Institute of Nanjing University of technology delivered protein drugs (angel. Chem. Int. ed., 2017, 56, 12481-12485) and mitochondrial targeted delivery proteins (angel. Chem. Int. ed., 2019, 58, 7657-7661) and other aspects have made a series of original research results, which has attracted wide attention of peers at home and abroad. Recently, he was invited to co write a review paper entitled "smart design of nanomaterials for mitochondria targeted nanotherapeutics" at angel. Chem. Int. ed. According to the complex microenvironment of organism and the development of nano material carrier, this paper systematically summarizes the application progress of the design of intelligent multi-functional nano preparation for mitochondrial targeted therapy.
Firstly, this paper introduces the structure, function and related diseases of mitochondria. Then, the development history and application of mitochondrial targeting agents with different structures, such as small molecular compounds, polypeptides and transition metal complexes, are briefly described.
Then, according to the complex microenvironment in vivo and the unique physicochemical properties of nanomaterials, this paper summarizes the design and application of a series of intelligent multifunctional nanoparticles for mitochondrial targeting therapy. In this paper, we explain how to use charge conversion and layer by layer targeting strategy to prepare multifunctional nanoparticles to overcome many physiological barriers and reach mitochondria. And how to construct self-assembled nanoparticles or in-situ drug synthesis methods to overcome the problems of low drug loading rate and premature drug release. Then, the author focused on the types of mitochondrial targeted therapy, such as photodynamic therapy, photothermal therapy, up conversion photodynamic therapy, self supplied oxygen / ROS / RNs therapy, acoustic therapy and combination therapy, which can be used to treat tumor by acting on the mitochondrial site, or to treat neurodegenerative diseases by clearing the ROS inside the mitochondria. In addition, in view of the current research focus on protein drug / antibody mitochondrial delivery, the authors also made corresponding analysis according to the research results of the research group.
At the end of the paper, the author points out that in the face of the increasing development of mitochondrial medicine and future clinical application, there are still many problems to be solved. First of all, most of the current mitochondrial treatment strategies focus on tumor treatment by increasing ROS or delivering tumor drugs to mitochondria, while the treatment methods for mitochondrial related neurodegenerative diseases (Parkinson's disease and Alzheimer's disease) are relatively few; secondly, most researchers use triphenylphosphine TPP as a ligand and nanoparticle coupling for line therapy Particle targeting, which has some limitations, needs to develop more new mitochondrial targeting groups with low toxicity and side effects to meet the diverse needs of mitochondrial delivery in the future. The delivery of protein drugs and antibodies to mitochondria has achieved preliminary results, but the delivery efficiency and controlled release need to be further optimized. To solve these problems, we need to design a more sophisticated and intelligent subcellular multifunctional nanosystem in the future, improve the treatment efficiency and accelerate the clinical transformation of mitochondrial medicine.
This achievement was recently published in Angewandte Chemie International Edition. The first author of this article is Liew Sisi of National University of Singapore and Dr. Qin Xiaofei (co communication) of Advanced Materials Research Institute of Nanjing University of technology.
Smart design of nanomaterials for mitochondria targeted nanotherapeuticssi Si Liew, Xiaofei Qin *, Jia Zhou, Lin Li *, Wei Huang, Shao Q. Yao * angle. Chem. Int. ed., 2020, DOI: 10.1002/anie.201915826
About Professor Li Lin
Professor Li Lin's research group focuses on Biomedical Photonics Research of "mitochondrial optical detection and regulation", covering photonics / organic chemistry / Biomedical Engineering, focusing on the application of new methods of mitochondrial specific pathological biological system development in early diagnosis and treatment and the development of new drugs. At the molecular level and in vivo level, the role of small molecule fluorescent probes in the detection and regulation of protein activity was revealed. At the same time, at the gene level, the great application prospects of this kind of light functional small molecule biological functional regulators in the fields of disease diagnosis, signal transduction and drug development were described. So far, it has been in nature communications, accounts of chemical research, Journal of the American Chemical Society, Angewandte Chemistry International Edition, Advanced materials and other journals published more than 80 SCI collected papers as the first / corresponding author, applied for / authorized 40 / 6 patents, participated in the compilation of a monograph molecular imaging and accurate diagnosis, presided over 7 national / provincial scientific research projects, and participated in an enterprise commissioned project. He was successively elected as the spokesperson of element MC of Chinese young chemist element periodic table, the young member of Biomedical Photonics branch of China biomedical engineering society, the young member of active oxygen biological effect Professional Committee of China Environmental Mutagen Society, the Editorial Committee of material guide, Chinese chemical Young editorial board member of letters, young editorial board member of Chinese clinical pharmacology and therapeutics, visiting researcher of NNI, etc.
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