Koo Chul Kwon  Ho Kyung Ko  Jiyun Lee  Eun Jung Lee  Kwangmeyung Kim  Jeewon Lee 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(31):4241-4253

Human ferritin heavy‐chain nanoparticle (hFTH) is genetically engineered to present tumor receptor‐binding peptides (affibody and/or RGD‐derived cyclic peptides, named 4CRGD here) on its surface. The affibody and 4CRGD specifically and strongly binds to human epidermal growth factor receptor I (EGFR) and human integrin αvβ3, respectively, which are overexpressed on various tumor cells. Through in vitro culture of EGFR‐overexpressing adenocarcinoma (MDA‐MB‐468) and integrin‐overexpressing glioblastoma cells (U87MG), it is clarified that specific interactions between receptors on tumor cells and receptor‐binding peptides on engineered hFTH is critical in active tumor cell targeting. After labeling with the near‐infrared fluorescence dye (Cy5.5) and intravenouse injection into MDA‐MB‐468 or U87MG tumor‐bearing mice, the recombinant hFTHs presenting either peptide or both of affibody and 4CRGD are successfully delivered to and retained in the tumor for a prolonged period of time. In particular, the recombinant hFTH presenting both affibody and 4CRGD notably enhances in vivo detection of U87MG tumors that express heterogeneous receptors, integrin and EGFR, compared to the other recombinant hFTHs presenting either affibody or 4CRGD only. Like affibody and 4CRGD used in this study, other multiple tumor receptor‐binding peptides can be also genetically introduced to the hFTH surface for actively targeting of in vivo tumors with heterogenous receptors.  相似文献   

    

Wei Tang  Zipeng Zhen  Mengzhe Wang  Hui Wang  Yen‐Jun Chuang  Weizhong Zhang  Geoffrey D Wang  Trever Todd  Taku Cowger  Hongmin Chen  Lin Liu  Zibo Li  Jin Xie 《Advanced functional materials》2016,26(11):1757-1768

Photodynamic therapy (PDT) is a promising treatment modality for cancer management. So far, most PDT studies have focused on delivery of photo­sensitizers to tumors. O₂, another essential component of PDT, is not artificially delivered but taken from the biological milieu. However, cancer cells demand a large amount of O₂ to sustain their growth and that often leads to low O₂ levels in tumors. The PDT process may further potentiate the oxygen deficiency, and in turn, adversely affect the PDT efficiency. In the present study, a new technology called red blood cell (RBC)‐facilitated PDT, or RBC‐PDT, is introduced that can potentially solve the issue. As the name tells, RBC‐PDT harnesses erythrocytes, an O₂ transporter, as a carrier for photosensitizers. Because photosensitizers are adjacent to a carry‐on O₂ source, RBC‐PDT can efficiently produce ¹O₂ even under low oxygen conditions. The treatment also benefits from the long circulation of RBCs, which ensures a high intraluminal concentration of photosensitizers during PDT and hence maximizes damage to tumor blood vessels. When tested in U87MG subcutaneous tumor models, RBC‐PDT shows impressive tumor suppression (76.7%) that is attributable to the codelivery of O₂ and photosensitizers. Overall, RBC‐PDT is expected to find wide applications in modern oncology.  相似文献   

    

Zulzikry Hafiz Abu Bakar  Jean-Pierre Bellier  Daijiro Yanagisawa  Tomoko Kato  Ken-ichi Mukaisho  Ikuo Tooyama 《International journal of molecular sciences》2022,23(1)

Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal novel aspects of the pathology. Immunohistochemistry was used to assess the distribution and abnormal changes in FtMt and LC3 immunoreactivities. Colocalization analysis using double immunofluorescence was performed, and subcellular patterns were examined using 3D imaging and modeling. In the substantia nigra pars compacta (SNc), strong FtMt-IR and LC3-IR were observed in the neurons of PSP patients. In other midbrain regions, such as the superior colliculus, the FtMt-IR and LC3-IR remained unchanged. In the SNc, nigral neurons were categorized into four patterns based on subcellular LC3/FtMt immunofluorescence intensities, degree of colocalization, and subcellular overlapping. This categorization suggested that concomitant accumulation of LC3/FtMt is related to mitophagy processes. Using the LC3-IR to stage neuronal damage, we retraced LC3/FtMt patterns and revealed the progression of FtMt accumulation in nigral neurons. Informed by these findings, we proposed a hypothesis to explain the function of FtMt during PSP progression.  相似文献   

    

Ana C. Moreira  Tnia Silva  Gonalo Mesquita  Ana Cordeiro Gomes  Clara M. Bento  Joo V. Neves  Daniela F. Rodrigues  Pedro N. Rodrigues  Agostinho A. Almeida  Paolo Santambrogio  Maria Salom Gomes 《International journal of molecular sciences》2022,23(1)

During infections, the host redistributes iron in order to starve pathogens from this nutrient. Several proteins are involved in iron absorption, transport, and storage. Ferritin is the most important iron storage protein. It is composed of variable proportions of two peptides, the L- and H-ferritins (FTL and FTH). We previously showed that macrophages increase their expression of FTH1 when they are infected in vitro with Mycobacterium avium, without a significant increase in FTL. In this work, we investigated the role of macrophage FTH1 in M. avium infection in vivo. We found that mice deficient in FTH1 in myeloid cells are more resistant to M. avium infection, presenting lower bacterial loads and lower levels of proinflammatory cytokines than wild-type littermates, due to the lower levels of available iron in the tissues. Importantly, we also found that FTH1 produced by myeloid cells in response to infection may be found in circulation and that it plays a key role in iron redistribution. Specifically, in the absence of FTH1 in myeloid cells, increased expression of ferroportin is observed in liver granulomas and increased iron accumulation occurs in hepatocytes. These results highlight the importance of FTH1 expression in myeloid cells for iron redistribution during infection.  相似文献   

    

Yao Cai  Tian Deng  Yongxin Pan  Jeffrey I. Zink 《Advanced functional materials》2020,30(39)

Mesoporous silica nanoparticles (MSNs) functionalized with redox‐sensitive or pH‐sensitive nanovalves for doxorubicin delivery and release by using recombinant human H chain ferritin (HFn) as a cap have been designed and fabricated. In both cases, transmission electron microscope observatory, dynamic light scattering change, Fourier transform infrared spectra examination, thermogravimetric analysis show that HFn can be chemically bonded to MSNs while retaining its ability to target transferrin receptor 1 (TfR1). Cargo loading and release studies demonstrate that HFn is an efficient capping agent, blocking the pores of MSN preventing cargo molecules from diffusing out, and is responsive to redox stimuli or pH changes. More importantly, HFn can not only cap the MSNs, but also enables targeted cargo delivery to malignant cells by binding to the TfR1 that has been overexpressed in various tumors, which can be reflected by the cell viability and fluorescence microscope analysis results comparing with cyclodextrin as the capping agent and TfR1 blocking assay. The in vivo study reveals the excellent efficacy of doxorubicin loaded and HFn capped MSNs on suppression of tumor growth. The new developed drug delivery system features mutually benefit and mutually support, providing strategy for achieving specific‐site therapeutics delivery systems.  相似文献   

    

Ferran Celma Nos  Gonzalo Hernndez  Xnia Ferrer-Corts  Ines Hernandez-Rodriguez  Begoa Navarro-Almenzar  Jos Luis Fuster  Mar Bermúdez Corts  Santiago Prez-Montero  Cristian Tornador  Mayka Sanchez 《International journal of molecular sciences》2021,22(11)

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Marta Sevieri  Leopoldo Sitia  Arianna Bonizzi  Marta Truffi  Serena Mazzucchelli  Fabio Corsi 《International journal of molecular sciences》2021,22(4)

Indocyanine green (ICG) is a near infrared fluorescent tracer used in image-guided surgery to assist surgeons during resection. Despite appearing as a very promising tool for surgical oncology, its employment in this area is limited to lymph node mapping or to laparoscopic surgery, as it lacks tumor targeting specificity. Recently, a nanoformulation of this dye has been proposed with the aim toward tumor targeting specificity in order to expand its employment in surgical oncology. This nanosystem is constituted by 24 monomers of H-Ferritin (HFn), which self-assemble into a spherical cage structure enclosing the indocyanine green fluorescent tracer. These HFn nanocages were demonstrated to display tumor homing due to the specific interaction between the HFn nanocage and transferrin receptor 1, which is overexpressed in most tumor tissues. Here, we provide an ex vivo detailed comparison between the biodistribution of this nanotracer and free ICG, combining the results obtained with the Karl Storz endoscope that is currently used in clinical practice and the quantification of the ICG signal derived from the fluorescence imaging system IVIS Lumina II. These insights demonstrate the suitability of this novel HFn-based nanosystem in fluorescence-guided oncological surgery.  相似文献   

    

Xuanrong Sun  Yulu Hong  Yubei Gong  Shanshan Zheng  Dehui Xie 《International journal of molecular sciences》2021,22(13)

Ferritin naturally exists in most organisms and can specifically recognize the transferrin 1 receptor (TfR1), which is generally highly expressed on various types of tumor cells. The pH dependent reversible assembling and disassembling property of ferritin renders it as a suitable candidate for encapsulating a variety of anticancer drugs and imaging probes. Ferritins external surface is chemically and genetically modifiable which can serve as attachment site for tumor specific targeting peptides or moieties. Moreover, the biological origin of these protein cages makes it a biocompatible nanocarrier that stabilizes and protects the enclosed particles from the external environment without provoking any toxic or immunogenic responses. Recent studies, further establish ferritin as a multifunctional nanocarrier for targeted cancer chemotherapy and phototherapy. In this review, we introduce the favorable characteristics of ferritin drug carriers, the specific targeted surface modification and a multifunctional nanocarriers combined chemotherapy with phototherapy for tumor treatment. Taken together, ferritin is a potential ideal base of engineered nanoparticles for tumor therapy and still needs to explore more on its way.  相似文献   

    

Dr. Kourosh Honarmand Ebrahimi 《Chembiochem : a European journal of chemical biology》2021,22(8):1371-1378

Infectious diseases are a continues threat to human health and the economy worldwide. The latest example is the global pandemic of COVID-19 caused by SARS-CoV-2. Antibody therapy and vaccines are promising approaches to treat the disease; however, they have bottlenecks: they might have low efficacy or narrow breadth due to the continuous emergence of new strains of the virus or antibodies could cause antibody-dependent enhancement (ADE) of infection. To address these bottlenecks, I propose the use of 24-meric ferritin for the synthesis of mosaic nanocages to deliver a cocktail of antibodies or nanobodies alone or in combination with another therapeutic, like a nucleotide analogue, to mimic the viral entry process and deceive the virus, or to develop mosaic vaccines. I argue that available data showing the effectiveness of ferritin-antibody conjugates in targeting specific cells and ferritin-haemagglutinin nanocages in developing influenza vaccines strongly support my proposals.  相似文献   

    

Oliver Strbak  Lucia Balejcikova  Martina Kmetova  Jan Gombos  Jozef Kovac  Dusan Dobrota  Peter Kopcansky 《International journal of molecular sciences》2021,22(16)

Magnetite mineralization in human tissue is associated with various pathological processes, especially neurodegenerative disorders. Ferritin’s mineral core is believed to be a precursor of magnetite mineralization. Magnetoferritin (MF) was prepared with different iron loading factors (LFs) as a model system for pathological ferritin to analyze its MRI relaxivity properties compared to those of native ferritin (NF). The results revealed that MF differs statistically significantly from NF, with the same LF, for all studied relaxation parameters at 7 T: r₁, r₂, r₂*, r₂/r₁, r₂*/r₁. Distinguishability of MF from NF may be useful in non-invasive MRI diagnosis of pathological processes associated with iron accumulation and magnetite mineralization (e.g., neurodegenerative disorders, cancer, and diseases of the heart, lung and liver). In addition, it was found that MF samples possess very strong correlation and MF’s relaxivity is linearly dependent on the LF, and the transverse and longitudinal ratios r₂/r₁ and r₂*/r₁ possess complementary information. This is useful in eliminating false-positive hypointensive artefacts and diagnosis of the different stages of pathology. These findings could contribute to the exploitation of MRI techniques in the non-invasive diagnosis of iron-related pathological processes in human tissue.  相似文献