Target delivering paclitaxel by ferritin heavy chain nanocages for glioma treatment

Liu, Wei; Lin, Qing; Fu, Yu; Huang, Shiqi; Guo, Chengqi; Li, Lin; Wang, Leilei; Zhang, Zhirong; Zhang, Ling

doi:10.1016/j.jconrel.2019.12.010

Cited by 68 publications

(58 citation statements)

References 36 publications

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“…As demonstrated by a published report [ 18 , 35 ], HFn can actively cross the BBB through TfR1-mediated transcytosis; In addition, the contact binding sites between HFn and TfR1 were recently identified by Amédée des Georges and Beatrice Vallone with cryo-EM structure [ 36 ]. The HFn binding regions were among the external BC loop (R79, F81, Q83, K86, K87), the C-terminus of the C-helix (E116, K119.…”

Section: Resultsmentioning

confidence: 99%

“…One promising strategy for transporting drugs across the BBB barrier is to target endogenous receptors, such as nicotinic acetylcholine receptors, TfR1, the insulin receptor, and low-density lipoprotein receptors for RMT [ 40 ]. Among these receptors, TfR1-mediated transcytosis is a popular choice for transporting drugs across the BBB and into the desired CNS regions [ 18 , 35 , 40 ]. The innate ligand of TfR1 (CD71) is human HFn through binding to the BC loop of HFn [ 36 , 41 ], which is the primary reason why we chose to fabricate recombinant HFn for a glioma-targeting drug delivery system.…”

Section: Discussionmentioning

confidence: 99%

“…Intriguingly, modified 2D-HFn demonstrated the ultra-high drug encapsulation efficiency of 61.7%, which is over 5 times higher than that of HFn and the drug loading molecules per protein cage can even reach 458. Ling Ahang et al also reported that the higher affinity between paclitaxel (PTX) and HFn is the reason why the encapsulation efficiency of PTX-loaded HFn is higher than encapsulation with DOX, curcumin and Olaparib [ 35 ]. Thus, the higher loading ratio of DOX with 2D-HFn might be attributed to the modified integrin α2β1 targeting sequence, which possesses multiple carboxyl groups that may play a role in an ionic interaction between DOX and 2D-HFn.…”

Section: Discussionmentioning

confidence: 99%

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Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy

et al. 2021

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Background Ferritin, the natural iron storage protein complex, self-assembles into a uniform cage-like structure. Human H-ferritin (HFn) has been shown to transverse the blood–brain barrier (BBB) by binding to transferrin receptor 1 (TfR1), which is abundant in endothelial cells and overexpressed in tumors, and enters cells via endocytosis. Ferritin is easily genetically modified with various functional molecules, justifying that it possesses great potential for development into a nanocarrier drug delivery system. Results In this study, a unique integrin α2β1-targeting H-ferritin (2D-HFn)-based drug delivery system was developed that highlights the feasibility of receptor-mediated transcytosis (RMT) for glioma tumor treatment. The integrin targeting α2β1 specificity was validated by biolayer interferometry in real time monitoring and followed by cell binding, chemo-drug encapsulation stability studies. Compared with naïve HFn, 2D-HFn dramatically elevated not only doxorubicin (DOX) drug loading capacity (up to 458 drug molecules/protein cage) but also tumor targeting capability after crossing BBB in an in vitro transcytosis assay (twofold) and an in vivo orthotopic glioma model. Most importantly, DOX-loaded 2D-HFn significantly suppressed subcutaneous and orthotopic U-87MG tumor progression; in particular, orthotopic glioma mice survived for more than 80 days. Conclusions We believe that this versatile nanoparticle has established a proof-of-concept platform to enable more accurate brain tumor targeting and precision treatment arrangements. Additionally, this unique RMT based ferritin drug delivery technique would accelerate the clinical development of an innovative drug delivery strategy for central nervous system diseases with limited side effects in translational medicine. Graphic Abstract

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy

et al. 2021

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“…Consequently, interest in application of ferritin nanocage in drug delivery and MRI imaging has been increasing. [12,[37][38][39][40][41][42] Yet, its use for making antiviral mosaic nanocages to target viral particles has not been demonstrated. I will discuss four strategies to engineer ferritin and create antiviral mosaic nanocages as therapeutic candidates with the aim to address the current global pandemic of SARS-CoV-2.…”

Section: Ferritin Structure and Functionmentioning

confidence: 99%

“…The presence of ferritin heteropolymer in serum strongly suggests that the use of H‐ or L‐type ferritin nanocage for developing therapeutics is safe and would cause less toxicity as compared to synthetic nanoparticles. Consequently, interest in application of ferritin nanocage in drug delivery and MRI imaging has been increasing [12,37–42] . Yet, its use for making antiviral mosaic nanocages to target viral particles has not been demonstrated.…”

Section: Figurementioning

confidence: 99%

Ferritin as a Platform for Creating Antiviral Mosaic Nanocages: Prospects for Treating COVID‐19

Ebrahimi

2020

ChemBioChem

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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 antibodydependent enhancement (ADE) of infection. To address these bottlenecks, I propose the use of 24-meric ferritin for the

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Nanosonosensitizer‐Augmented Sono‐Immunotherapy for Glioblastoma by Non‐Invasive Opening of the Blood–Brain Barrier

Lin

Wang

Long

et al. 2022

Adv Funct Materials

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The presence of blood-brain barrier (BBB) that limits effective penetration of therapeutics is the main reason for poor outcomes of glioblastoma (GBM) treatment. Ultrasound (US) combined with microbubbles (MBs) can precisely disrupt the tight junctions of brain endothelial cells, thus creating "acoustic pores" and non-invasive opening the BBB. Here, chitosan oligosaccharide (COS) is conjugated with a sonosensitizer protoporphyrin IX (PpIX) and an immune-enhancing adjuvant Poly(I:C) via electrostatic adsorption, and crosslinked with a tumor-targeting molecule hyaluronic acid (HA) affording nanosonosensitizers HA-Poly(I:C)/COS-PpIX (abbreviated as "HP/CP" NSs). HP/ CP NSs can target and penetrate GBMs, and trigger reactive oxygen species production upon US, simultaneously causing mitochondrial dysfunction and DNA damage. Tumor-associated antigens released by sonodynamic therapyinduced immunogenic cell death and loaded Poly(I:C) form an in situ vaccine together to potentiate antitumor immune responses. In orthotopic GBM mice models, the HP/CP+US treatments prolong mice survival, enhance cytotoxic T-lymphocytes infiltration, and activate peripheral immune circulation. Besides, HP/CP NSs possess favorable biosafety profiles. Collectively, this study sheds light on the application of HP/CP NSs for synergistic sonoimmunotherapy of GBMs after non-invasive opening of the BBB.

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Target delivering paclitaxel by ferritin heavy chain nanocages for glioma treatment

Cited by 68 publications

References 36 publications

Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy

Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy

Ferritin as a Platform for Creating Antiviral Mosaic Nanocages: Prospects for Treating COVID‐19

Nanosonosensitizer‐Augmented Sono‐Immunotherapy for Glioblastoma by Non‐Invasive Opening of the Blood–Brain Barrier

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