2014至2023年国家自然科学基金生物医学工程/再生医学方向的资助情况分析

本文汇总2014—2023年国家自然科学基金委员会医学科学部在生物医学工程/再生医学方向面上项目、青年科学基金项目与地区科学基金项目(简称“面青地项目”)的申请与资助情况,同时分析近10年相关领域的文献报道热点,为该领域的进一步高水平发展提供参考依据。回顾性收集代码H28下面青地项目的申请与资助数据资料,主要包括:资助项数与资助经费、资助项目所在依托单位与省市分布、获资助申请人的年龄与职称分布、获资助项目申请书的关键词等内容。同时,基于Web of Science数据库对近10年发表的相关方向文献关键词进行汇总,利用CiteSpace 6.2.R4软件对关键词的热点聚类及时间分布进行分析。通过分析发现:在2014—2023年中,生物医学工程/再生医学方向共资助面青地项目1279项,包括面上项目623项、青年科学基金项目599项和地区科学基金项目57项,资助经费50799万元。其中2014年的资助项目数最少,2023年的资助项目数最多。该方向的项目资助主要集中在H2808、H2809及H2810,3个代码获资助项目数与经费总和分别占全部项目的65.9%及64.6%。上海市、上海交通大学分别是获资助项目数最多的地区、依托单位,分别占比14.7%和7.0%。31~35岁的申请人获资助项目数最多,共507项,占比39.6%。近10年该方向获资助面青地项目申请书中出现频率最高的中英文关键词都与纳米相关(纳米药物和nanomedicine),而在Web of Science数据库中已发表相关方向文献的热门关键词包括biomedical engineering、tissue engineering、biomedical applications等。近年来,国家自然科学基金委员会医学科学部对生物医学工程/再生医学方向面青地项目的资助呈稳步上升趋势,资助领域广泛且重点明确,逐步建立以青年科研人员为主体的人才梯队。

纳米材料助力合成生物学的生物医学应用

合成生物学是借助基因工具改造活细胞和生物体的学科,其经历了蓬勃发展阶段,在生物医学领域得到广泛应用,包括新型生物传感器和生物材料设计,以及最新临床治疗药物和疫苗的开发.纳米材料具有独特的物理、化学和生物特性,在拓展合成生物学的生物医学应用场景上具有巨大的潜力,可以提高治疗剂的生产效率,并增强改造生物体的功能.在此,我们简要概述了纳米材料应用于合成生物学领域的最新进展,主要涵盖纳米材料作为递送载体、信号转导器和功能增强剂的角色及其制备过程和性能特点.本综述首先强调了纳米材料作为基因载体的最新成果,包括有机、无机和仿生递送系统;其次,回顾了纳米材料介导的刺激响应型基因表达调控的研究;第三,总结了在可编程的杂化生物活性材料方面的开创性工作,包括纳米材料/细菌杂合系统和纳米材料/哺乳动物细胞杂合系统;最后,讨论了该领域当前面临的挑战,并从个人观点展望了未来的发展前景.

Advances of nanoparticles as drug delivery systems for disease diagnosis and treatment

Decades have passed since the first nanoparticles-base medicine was approved for human cancer treatment, and the research and development of nanoparticles for drug delivery are always undergoing.Nowadays, the significant advances complicate nanoparticles’ branches, including liposomes, solid lipid nanoparticles, inorganic nanoparticles, micelles, nanovaccines and nano-antibodies, etc. These nanoparticles show numerous capabilities in treatment and diagnosis of stubborn diseases like cancer and neurodegenerative diseases, emerging as novel drug carriers or therapeutic agents in future. In this review, the complicated branches of nanoparticles are classified and summarized, with their property and functions concluded. Besides, there are also some delivery strategies that make nanoparticles smarter and more efficient in drug delivery, and frontiers in these strategies are also summarized in this review. Except these excellent works in newly-produced drug delivery nanoparticles, some points of view and future expectations are made in the end.

Nanotechnology-based strategies for treatment of ocular disease

Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops,injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new,highly effective and important ocular nanomedicines.

Color-tunable Gd-Zn-Cu-ln-S/ZnS quantum dots for dual modality magnetic resonance and fluorescence imaging

Inorganic nanoparticles have been introduced into biological systems as useful probes for in vitro diagnosis and in vivo imaging, due to their relatively small size and exceptional physical and chemical properties. A new kind of color- tunable Gd-Zn-Cu-In-S/ZnS （GZCIS/ZnS） quantum dots （QDs） with stable crystal structure has been successfully synthesized and utilized for magnetic resonance （MR） and fluorescence dual modality imaging. This strategy allows successful fabrication of GZCIS/ZnS QDs by incorporating Gd into ZCIS/ZnS QDs to achieve great MR enhancement without compromising the fluorescence properties of the initial ZCIS/ZnS QDs. The as-prepared GZCIS/ZnS QDs show high T1 MR contrast as well as ＂color-tunable＂ photoluminescence （PL） in the range of 550-725 nm by adjusting the Zn/Cu feeding ratio with high PL quantum yield （QY）. The GZCIS/ZnS QDs were transferred into water via a bovine serum albumin （BSA） coating strategy. The resulting Cd-free GZCIS/ZnS QDs reveal negligible cytotoxicity on both HeLa and A549 cells. Both fluorescence and MR imaging studies were successfully performed in vitro and in vivo. The results demonstrated that GZCIS/ZnS QDs could be a dual-modal contrast agent to simultaneously produce strong MR contrast enhancement as well as fluorescence emission for in vivo imaging.

Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication

Nowadays,nanotechnology is revolutionizing the approaches to different fields from manufacture to health.Carbon nanotubes(CNTs)as promising candidates in nanomedicine have great potentials in developing novel entities for central nervous system pathologies,due to their excellent physicochemical properties and ability to interface with neurons and neuronal circuits.However,most of the studies mainly focused on the drug delivery and bioimaging applications of CNTs,while neglect their application prospects as therapeutic drugs themselves.At present,the relevant reviews are not available yet.Herein we summarized the latest advances on the biomedical and therapeutic applications of CNTs in vitro and in vivo for neurological diseases treatments as inherent therapeutic drugs.The biological mechanisms of CNTs-mediated bio-medical effects and potential toxicity of CNTs were also intensely discussed.It is expected that CNTs will exploit further neurological applications on disease therapy in the near future.

Biomimetic nanomedicines for precise atherosclerosis theranostics

Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are moving closer to fulfilling this need,pushing back the frontier of nano-based drug delivery systems design.This review seeks to outline how these nanomedicines(NMs)might work to diagnose and treat atherosclerosis,to trace the trajectory of their development to date and in the coming years,and to provide a foundation for further discussion about atherosclerotic theranostics.

Identification of SARS-CoV-2-against aptamer with high neutralization activity by blocking the RBD domain of spike protein 1

Dear Editor,The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)poses a great threat to the public health of people and the normal economic and social development around the world.As of January 8,2021,more than 88 million people were infected with SARS-CoV-2,resulting in more than 1.9 million death.

Gold nanoparticles combat enveloped RNA virus by affecting organelle dynamics

Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid(RNA).These viruses rely on host cell machinery and organelles to replicate and assemble new virus particles.However,the interaction between viruses and host organelles may be disrupted by nanomaterials,such as gold nanoparticles(AuNPs)with unique physical and chemical properties.In this study,we investigated the effects of AuNPs with different surface charge properties on the subcellular structure and function of mammalian cells,and their effects on two representative enveloped RNA viruses:lentivirus and human coronavirus OC43(HCoV-OC43)antiviral potential.By comparing the subcellular effects of AuNPs with different surface charge properties,we found that treatment with AuNPs with positive surface charges induced more significant disruption of subcellular structures than neutrally charged AuNPs and negatively charged AuNPs,mainly manifested in lysosomes and Cytoskeletal disorders.The antiviral effect of the surface positively charged AuNPs was further evaluated using lentivirus and HCoV-OC43.The results showed that AuNPs had a significant inhibitory effect on both lentivirus and HCoV-OC43 without obvious side effects.In conclusion,our study provides insights into the mechanism of action and biocompatibility of AuNP in biological systems,while supporting the potential of targeting organelle dynamics against enveloped RNA viruses.

Inflammation responsive tofacitinib loaded albumin nanomedicine for targeted synergistic therapy in ulcerative colitis

Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting systemic side effects including infections,cancers and lymphoma limit its popularity of clinical application.This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1(anti-MAdCAM-1)antibody modified reactive oxygen species(ROS)responsive human serum albumin-based nanomedicine denoted as THM,to improve the therapeutic efficacy of tofacitinib for UC treatment.THM has the drug releasing properties in response to ROS stimulation.In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages.Meanwhile,the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing.In addition,in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon.Moreover,THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis.This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.

Engineered nanoparticles circumvent the adaptive treatment tolerance to immune-checkpoint blockade therapy

The fight against cancer has witnessed the rapid develop・ment of various therapeutic methodologies,including chemotherapy,surgery,radiotherapy,phototherapy,and the emerging immunotherapy[1].However,malignancies evolve adaptive tolerance under the threatening conditions upon therapies because of some potential biological or genetic mutations,which may cause serious adverse events,compromised therapeutic efficacy and even treatment failure.For instance,following the standard chemotherapy with paclitaxel,primary breast cancer can release exosomes that facilitate the seeding and growth of metastatic cancer cells in distant organs[2].Therefore,the term"adaptive treatment tolerance"(ATT),rather than"drug resistance",has been employed to better describe the dynamic evolution of this phenomenon during/post cancer therapy.

Osteopontin targeted theranostic nanoprobes for laser-induced synergistic regression of vulnerable atherosclerotic plaques

Vulnerable atherosclerotic plaque(VASPs)is the major pathological cause of acute cardiovascular event.Early detection and precise intervention of VASP hold great clinical significance,yet remain a major challenge.Photodynamic therapy(PDT)realizes potent ablation efficacy under precise manipulation of laser irradiation.In this study,we constructed theranostic nanoprobes(NPs),which could precisely regress VASPs through a cascade of synergistic events triggered by local irradiation of lasers under the guidance of fluorescence/MR imaging.The NPs were formulated from human serum albumin(HSA)conjugated with a high affinity-peptide targeting osteopontin(OPN)and encapsulated with photosensitizer IR780 and hypoxia-activatable tirapazamine(TPZ).After intravenous injection into atherosclerotic mice,the OPN-targeted NPs demonstrated high specific accumulation in VASPs due to the overexpression of OPN in activated foamy macrophages in the carotid artery.Under the visible guidance of fluorescence and MR dual-model imaging,the precise near-infrared(NIR)laser irradiation generated massive reactive oxygen species(ROS),which resulted in efficient plaque ablation and amplified hypoxia within VASPs.In response to the elevated hypoxia,the initially inactive TPZ was successively boosted to present potent biological suppression of foamy macrophages.After therapeutic administration of the NPs for 2 weeks,the plaque area and the degree of carotid artery stenosis were markedly reduced.Furthermore,the formulated NPs displayed excellent biocompatibility.In conclusion,the developed HSA-based NPs demonstrated appreciable specific identification ability of VASPs and realized precise synergistic regression of atherosclerosis.

NVP-BEZ235/Chlorin-e6 co-loaded nanoparticles ablate breast cancer by biochemical and photodynamic synergistic effects

Seeking profitable therapies for triple-negative breast cancer （TNBC） has attracted intense research interest. However, an efficient cure for TNBC remains an unresolved challenge in oncology. Herein, for the first time, we describe the use of polymeric nanoparticles loaded with NVP-BEZ235 and Chlorin-e6, denoted as NVP/Ce6@NPs, to overcome the adaptive treatment tolerance of TNBC by taking advantage of the synergistic effect .between biochemical and photodynamic therapies. Upon laser irradiation, the NVP/Ce6@NPs generated reactive oxygen species （ROS） and efficiently induced the apoptosis of tumor cells through DNA damage. Furthermore, the released NVP-BEZ235 could prevent Chkl phosphorylation-induced DNA damage repair, thus enhancing the sensitivity of tumor cells to ROS. Animal studies on mice bearing an MDA-MB-231 tumor validated that the NVP/Ce6@NPs had a greater therapeutic efficacy compared to that of monotherapies, with an inhibition ratio of 89.3%. Western blotting and cell viability analyses confirmed the inhibition of both MDA-MB-231 cell proliferation and Chkl phosphorylation by NVP/Ce6@NPs. These findings provide a rational understanding of the synergistic effect of the biochemical/photodynamic therapy and pave the way for the development of efficient therapeutic approaches to fight against TNBC.

Modulation of Conformational Transition of Polypeptides under Slightly Acidic Environment

Controlling the conformational transition of polypeptides under slightly acidic environment is challenging.Herein,we report a class of pH-responsive helix-to-coil conformationally transitionable polypeptides(pCTPs)by simply conjugating tertiary amine groups(TAs)to polylysine.Their conformation is highly dependent on the charge state of TAs,showing a helical structure when most TAs are deprotonated and a non-helical structure when majority of TAs are protonated.The conformational transition pH can be modulated by tuning the hydrophobicity of TAs and the incorporation of hydrophobic monomers at a pH range of 7.2 to 6.0.Such pCTP showed a vesicle-to-micelle transition when their conformation transformed from helix to coil,facilitating controlled drug release.Our study provided an approach to control the conformational transition of polypeptides under slightly acidic condition.