Professor Hu Yong and Jiang Xiqun from Nanjing University: Recent advances in nanomaterials capable of overcoming biological barriers for tumor treatment

[ Introduction ]

The rapid development of nanotechnology has made amazing contributions to the development of tumor treatment. From early attempts to use organic vesicles as drug delivery vehicles to the latest methods using engineering materials themselves as therapeutic agents, nanomedicines are considered to be one of the most promising tools for treating tumors. However, relatively few nanomedicines can actually be used in clinical trials today. Part of the reason is related to the long-term exposure of organisms to the safety of nano-engineered materials. With a deep understanding of nanotoxicity, we have made significant progress in this area. Due to the lack of consideration of the complexity of the tumor‘s physiological environment, the current research on nanomedicines does not yet explain why most nanomedicines fail to achieve the expected efficacy in clinical trials. Early nanomedicine research believed that the successful delivery of nanomedicines to the location of solid tumors was the ultimate goal of nanomedicines to exert anti-cancer effects. But recent research has shown that tumors are heterogeneous, with many biological barriers that help to resist nano drug delivery and penetration. Therefore, even if the nano-drug is successfully delivered to tumor tissue, it does not necessarily indicate that the nano-drug can exert an ideal anti-tumor effect. These new findings prompted researchers to re-examine the design and preparation of nanomedicine diagnosis and treatment platforms, which in turn promoted the emergence of second-generation nanomedicines. We need to consider the impact of certain pathological features of solid tumors (such as the acidic microenvironment) on the delivery, drug release, and biological effects of the nanomedicine during the development of the nanomedicine to avoid premature release of the payload; on this basis Targeted changes in the structure and properties of the nanopharmaceutical make it beneficial to the penetration of tumor tissue and subsequent internalization of cells.

[ Achievement Profile ]

Professor Hu Yong and Professor Jiang Xiqun of Nanjing University summarized advanced strategies that are expected to overcome the many biological obstacles faced by nanomedicines. Starting from the entry of nano-drugs into tumors, the author systematically describes various methods to promote the penetration of nano-drug tissues and solve tumor hypoxia. It highlights the important impact of overcoming tumor physical obstacles and tumor biological characteristics on the design of nano-drugs. The advantages and disadvantages of the method are discussed in depth. The paper also discusses in detail the technical issues related to the preparation and use of nanopharmaceuticals, and the importance of balancing the value of treatment with the additional cost of complex nanopharmaceutical design. The achievements under the title " Recent in Advances in Nanostrategies Capable of Overcoming Barriers for Biological Tumor Management " published in the internationally renowned journal Adv. Mater. On .

[Picture and text guide]

Figure 1. Schematic representation of a representative biological barrier for nanomedicine

Figure 2. Schematic of the mechanism of normalizing tumor blood vessels using sensitizing radiation

Figure 3. This schematic shows a clustered bomb-like component ( WOACC ) composed of modified W ₁₈ O ₄₉ nanoparticles ( WOAC ), which can solve the deep penetration problem of nano-drugs in the tumor

Figure 4. Schematic showing how blocked oxygen consumption enhances the effect of photosensitizers

Figure 5.Cerenkov radiation

a) Cerenkov radiation-mediated generation of hydroxyl groups and superoxide radicals on the surface of TiO ₂ nanoparticles mediated by Cerenkov radiation b) Cerenkov radiation-induced titanocene excitation, which generates cyclopentadienyl and Titanium-centered free radicals

Figure 6. Characteristic composition of a single nanoparticle of a protein corona coating

Figure 7. Coarse-grain simulation results

a) Schematic diagram showing the geometry of the ellipsoidal particles used in the simulation

b) Reveal the difference in driving force required for the ellipsoid to pass through the lipid bilayer

cd) Calculation results show displacement of the ellipsoid interacting with the lipid bilayer in vertical and horizontal directions

Figure 8.2-Cyclobenzothiazole conjugated paclitaxel derivative with paclitaxel cleavable sequence constructed therein

a) Chemical structure of CBT conjugated paclitaxel molecule

b) Schematic showing intracellular formation of paclitaxel nanoparticles driven by furin

9. The functionalized with a targeting peptide melanoma PEG silica nanoparticles

a) Structure of 6 nm silica-based dots modified by cancer cell targeting peptides

b) The antitumor properties of the nanoparticles on mice received the empty vector as a control

Figure 10. Design of a tunable polymer micelle that undergoes two stages of surface property changes, allowing it to sequentially bypass the barriers of the lysosome and nuclear pore

【to sum up】

In this article, the author discusses several major physiological barriers to nanomedicine and strategies developed to overcome them. Currently, most nanomedicine research focuses on two or three obstacles, depending on the importance of the identified obstacles. Ideally, we can design a platform to overcome all the biological obstacles mentioned above. However, this design greatly increases the complexity of the system. We should keep in mind the design of nanopharmaceuticals that each physiological disorder has a different meaning in tumors of different types, sizes, locations, and stages. Therefore, it is necessary to balance costs, comprehensive challenges, and potential practical advantages to achieve the intended application. For example, if we need to successfully deliver a sufficient number of nanoparticles to larger solid tumors, we need a nano-drug platform with good tissue penetration, and we need more priority when treating millimeter-sized metastatic nodules. Choose a nanomedicine that has good free-diffusion ability rather than penetrating power in a narrow lymphatic system. We have exemplified this system in the article: with the help of matrix remodeling therapy or the platform itself, nanomedicines targeting pancreatic ductal adenocarcinoma are expected to bypass the dense matrix and directly enter the metastatic nodules . However, this process becomes less important when nanomedicines are needed to treat primary cancers with limited fibrotic components in the colon or brain tumors where the blood-brain barrier acts as a matrix. Similarly, this design principle is applicable to the preparation of a nanomedicine diagnosis and treatment platform that overcomes intracellular obstacles. If a certain type of nano-drug platform exerts a tumoricidal effect by regulating the tumor site, the lysosomal escape process of the nano-drug need not be considered. The authors suggest that when designing a multifunctional nanomedicine diagnosis and treatment platform, we should base on the expected application of nanomedicines, especially the pathological characteristics of tumors in certain specific situations, and start from solving the key obstacles faced by nanomedicines. Consider a reasonable combination of modules necessary to overcome these obstacles. Based on the above design ideas, we look forward to seeing a large number of nanomedicines that can enter the clinic in the future, bringing new hope for tumor treatment.

Literature link : Recent Advances in Nanostrategies Capable of Overcoming Biological Barriers for Tumor Management . Nano Energy , Advanced Materials, 2019, DOI: 10.1002 / adma.201904337

Dr. Hu Yong, Professor and PhD Supervisor, Department of Biomedical Engineering, Nanjing University, Young and Middle-aged Academic Leader of "Blue Project" in Jiangsu Province, and "Humboldt Scholar" in Germany have long been engaged in the research of nanomedicine carriers and nanoimaging materials and developed a series of More than 70 papers published in journals such as Nature Communication, Advanced Materials, Angew Chem., ACS Nano, Advanced Functional Materials, Biomaterials, and other nanomedicine diagnosis and treatment systems sensitive to tumor microenvironment (acid, enzyme, hypoxia, and tumor immunosuppression) > 3500 times), won the first prize of the Natural Science Award of the Ministry of Education, the second prize of the Science and Technology Progress Award of the Ministry of Education, and presided over a number of National Natural Science Funds and national key research and development plans.

Source of information: material cattle