Genetically engineered magnetic nanocages for cancer magneto-catalytic theranostics

磁热疗法是一种利用磁热敏剂在磁场中把磁能转换为热能以杀死肿瘤的新型癌症治疗方法，并已成功应用于临床。但是，目前临床所用磁热敏剂的磁-热转换效率低而使得治疗剂量过大，从而给病人带来潜在的副作用，因此大大限制了磁热疗法的广泛应用。该研究利用基因工程和仿生矿化技术制备出具有优异磁-热转化能力及纳米酶催化性能的磁性蛋白纳米笼（eMIONs），成功克服了临床磁热疗法中磁热敏剂低效的瓶颈，为新一代磁热敏剂的研发提供新的思路。该研究工作在刘刚教授指导下完成，博士生张阳为文章第一作者。【Abstract】The clinical applications of magnetic hyperthermia therapy (MHT) have been largely hindered by the poor magnetic-to-thermal conversion efficiency of MHT agents. Herein, we develop a facile and efficient strategy for engineering encapsulin-produced magnetic iron oxide nanocomposites (eMIONs) via a green biomineralization procedure. We demonstrate that eMIONs have excellent magnetic saturation and remnant magnetization properties, featuring superior magnetic-to-thermal conversion efficiency with an ultrahigh specific absorption rate of 2390 W/g to overcome the critical issues of MHT. We also show that eMIONs act as a nanozyme and have enhanced catalase-like activity in the presence of an alternative magnetic field, leading to tumor angiogenesis inhibition with a corresponding sharp decrease in the expression of HIF-1α. The inherent excellent magnetic-heat capability, coupled with catalysis-triggered tumor suppression, allows eMIONs to provide an MRI-guided magneto-catalytic combination therapy, which may open up a new avenue for bench-to-bed translational research of MHT.This work was supported by the Major State Basic Research Development Program of China (2017YFA0205201), the National Natural Science Foundation of China (81925019, 81422023, 81603015, 81871404, and U1705281), the Fundamental Research Funds for the Central Universities (20720190088 and 20720200019), and the Program for New Century Excellent Talents in University, China (NCET-13-0502). We acknowledge Jingru Huang and Baoying Xie from Central Laboratory in School of Medicine, Xiamen University, for assistance with inductively coupled plasma experiments and data analysis. 研究工作得到了科技部重大专项课题、973课题、国家自然科学基金委杰出青年基金等项目的支持

Human Serum Albumin Based Nanodrug Delivery Systems: Recent Advances and Future Perspective

With the success of several clinical trials of products based on human serum albumin (HSA) and the rapid development of nanotechnology, HSA-based nanodrug delivery systems (HBNDSs) have received extensive attention in the field of nanomedicine. However, there is still a lack of comprehensive reviews exploring the broader scope of HBNDSs in biomedical applications beyond cancer therapy. To address this gap, this review takes a systematic approach. Firstly, it focuses on the crystal structure and the potential binding sites of HSA. Additionally, it provides a comprehensive summary of recent progresses in the field of HBNDSs for various biomedical applications over the past five years, categorized according to the type of therapeutic drugs loaded onto HSA. These categories include small-molecule drugs, inorganic materials and bioactive ingredients. Finally, the review summarizes the characteristics and current application status of HBNDSs in drug delivery, and also discusses the challenges that need to be addressed for the clinical transformation of HSA formulations and offers future perspectives in this field

Active-oxygenating hollow Prussian blue nanosystems loaded with biomacromolecules for photodynamic/photothermal therapy of cancer and alleviating hypoxic tumors

Such is the hypoxia in solid tumor that Ⅱ-type photodynamic therapy (PDT) has not yet achieved significantly satisfactory consequences. Despite the rapid advancement in nanotechnology-based PDT for alleviating the hypoxic tumor microenvironment, several challenges persist. These include inefficient passive oxygen-supply mechanisms, low stability of oxygen-delivery nanosystems, and the complexity of their modification processes. To address these issues, we developed integrative nanoformulations (HHI NPs) by sequentially inserting biomacromolecule hemoglobin (Hb) and IR783 (photosensitizer) into hollow mesoporous Prussian blue (HPB NPs) through a straightforward and gentle diffusion method. Intriguingly, the resulting hybrid nanocomposites based on hollow mesoporous structure provided stability of biomacromolecule Hb, ensuring active and efficient oxygen delivery. In these nanosystems, HHI NPs equipped with high oxygen-carrying Hb efficiently generated reactive oxygen species over HepG2 cells cultured in hypoxic condition under NIR irradiation. Additionally, HPB NPs served not only as nanocarriers but also as photothermal agents exhibiting excellent photothermal conversion effects. which were beneficial for photothermal therapy (PTT) of cancer. HHI NPs co-loaded with Hb and IR783 not only actively relieved the hypoxic TME through the stable protection of the hollow structure from HPB NPs, but also achieve the significant synergistic therapy by combining PDT and PTT for tumor treatment

Enhancing the Efficiency of Mild-Temperature Photothermal Therapy for Cancer Assisting with Various Strategies

Conventional photothermal therapy (PTT) irradiates the tumor tissues by elevating the temperature above 48 °C to exert thermal ablation, killing tumor cells. However, thermal ablation during PTT harmfully damages the surrounding normal tissues, post-treatment inflammatory responses, rapid metastasis due to the short-term mass release of tumor-cellular contents, or other side effects. To circumvent this limitation, mild-temperature photothermal therapy (MTPTT) was introduced to replace PTT as it exerts its activity at a therapeutic temperature of 42–45 °C. However, the significantly low therapeutic effect comes due to the thermoresistance of cancer cells as MTPTT figures out some of the side-effects issues. Herein, our current review suggested the mechanism and various strategies for improving the efficacy of MTPTT. Especially, heat shock proteins (HSPs) are molecular chaperones overexpressed in tumor cells and implicated in several cellular heat shock responses. Therefore, we introduced some methods to inhibit activity, reduce expression levels, and hinder the function of HSPs during MTPTT treatment. Moreover, other strategies also were emphasized, including nucleus damage, energy inhibition, and autophagy mediation. In addition, some therapies, like radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, exhibited a significant synergistic effect to assist MTPTT. Our current review provides a basis for further studies and a new approach for the clinical application of MTPTT

Thermogravimetry study of the pyrolytic characteristics and kinetics of macro-algae Macrocystis pyrifera residue

Macrocystis pyrifera is one important marine macro-algae, while its residues produced by industrial alginate extraction is a hot potato. To figure out whether its residue is suitable for pyrolysis for biofuel, the pyrolytic characteristics and kinetics of macro-algae M. pyrifera residue was investigated using thermogravimetric method from 50 to 800 A degrees C in an inert argon atmosphere at different heating rates of 5, 10, 20, and 30 A degrees C min(-1). The activation energy and pre-exponential factor was calculated by Flynn-Wall-Ozawa, Kissinger-Akahira-Sunose, and Popescu methods, and the kinetic mechanism was deduced by Popescu method. The results showed that the primary devolatilization stage of M. pyrifera residue can be described by Jander function . The average activation energy of M. pyrifera residue was 222.4 kJ mol(-1). The results suggested that the experimental results and kinetic parameters provided useful information for the design of pyrolytic processing system using M. pyrifera residue as feedstock.Macrocystis pyrifera is one important marine macro-algae, while its residues produced by industrial alginate extraction is a hot potato. To figure out whether its residue is suitable for pyrolysis for biofuel, the pyrolytic characteristics and kinetics of macro-algae M. pyrifera residue was investigated using thermogravimetric method from 50 to 800 A degrees C in an inert argon atmosphere at different heating rates of 5, 10, 20, and 30 A degrees C min(-1). The activation energy and pre-exponential factor was calculated by Flynn-Wall-Ozawa, Kissinger-Akahira-Sunose, and Popescu methods, and the kinetic mechanism was deduced by Popescu method. The results showed that the primary devolatilization stage of M. pyrifera residue can be described by Jander function . The average activation energy of M. pyrifera residue was 222.4 kJ mol(-1). The results suggested that the experimental results and kinetic parameters provided useful information for the design of pyrolytic processing system using M. pyrifera residue as feedstock

Cancer cytomembrane-cloaked Prussian blue nanoparticles enhance the efficacy of mild-temperature photothermal therapy by disrupting mitochondrial functions of cancer cells

Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications