scholarly journals Designed ferritin nanocages displaying trimeric TRAIL and tumor-targeting peptides confer superior anti-tumor efficacy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jae Do Yoo ◽  
Sang Mun Bae ◽  
Junyoung Seo ◽  
In Seon Jeon ◽  
Sri Murugan Poongkavithai Vadevoo ◽  
...  
Keyword(s):  
Half Life ◽  
Tumor Targeting ◽  
Threefold Axis ◽  
Apoptosis Pathway ◽  
Cancer Models ◽  
Promising Target ◽  
Extrinsic Apoptosis ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide

AbstractTRAIL is considered a promising target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors, DR4 or DR5. Although recombinant human TRAIL has shown high potency and specificity for killing cancer cells in preclinical studies, it has failed in multiple clinical trials for several reasons, including a very short half-life mainly caused by instability of the monomeric form of TRAIL and rapid renal clearance of the off-targeted TRAIL. To overcome such obstacles, we developed a TRAIL-active trimer nanocage (TRAIL-ATNC) that presents the TRAIL ligand in its trimer-like conformation by connecting it to a triple helix sequence that links to the threefold axis of the ferritin nanocage. We also ligated the tumor-targeting peptide, IL4rP, to TRAIL-ATNC to enhance tumor targeting. The developed TRAIL-ATNCIL4rP showed enhanced agonistic activity compared with monomeric TRAIL. The in vivo serum half-life of TRAIL-ATNCIL4rP was ~ 16-times longer than that of native TRAIL. As a consequence of these properties, TRAIL-ATNCIL4rP exhibited efficacy as an anti-tumor agent in vivo against xenograft breast cancer as well as orthotopic pancreatic cancer models, highlighting the promise of this system for development as novel therapeutics against cancer.

scholarly journals Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 521
Author(s):  
Shuang Yin ◽  
Yan Wang ◽  
Bingyang Zhang ◽  
Yiran Qu ◽  
Yongdong Liu ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Half Life ◽  
Tumor Targeting ◽  
Drug Carrier ◽  
Life Extension ◽  
Sprague Dawley ◽  
Functional Peptides ◽  
Targeting Peptide

Ferritin, one of the most investigated protein nanocages, is considered as a promising drug carrier because of its advantageous stability and safety. However, its short half-life and undesirable tumor targeting ability has limited its usage in tumor treatment. In this work, two types of functional peptides, half-life extension peptide PAS, and tumor targeting peptide RGDK (Arg-Gly-Asp-Lys), are inserted to human heavy-chain ferritin (HFn) at C-terminal through flexible linkers with two distinct enzyme cleavable sites. Structural characterizations show both HFn and engineered HFns can assemble into nanoparticles but with different apparent hydrodynamic volumes and molecular weights. RGDK peptide enhanced the internalization efficiency of HFn and showed a significant increase of growth inhibition against 4T1 cell line in vitro. Pharmacokinetic study in vivo demonstrates PAS peptides extended ferritin half-life about 4.9 times in Sprague Dawley rats. RGDK peptides greatly enhanced drug accumulation in the tumor site rather than in other organs in biodistribution analysis. Drug loaded PAS-RGDK functionalized HFns curbed tumor growth with significantly greater efficacies in comparison with drug loaded HFn.

A chimera of green fluorescent protein with gelatinase binding and tumor targeting peptide

2010 ◽  
Vol 72 (2) ◽  
pp. 234-237 ◽  
Author(s):  
Justus Reunanen ◽  
Tanja-Maria Ranta ◽  
Oula Peñate-Medina ◽  
Juho Suojanen ◽  
Timo Sorsa ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Tumor Targeting ◽  
Fluorescent Protein ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide ◽  
Green Fluorescent

GRPR-targeted SPECT imaging using a novel bombesin-based peptide for colorectal cancer detection

2020 ◽  
Vol 8 (23) ◽  
pp. 6764-6772 ◽  
Author(s):  
Peifei Liu ◽  
Yuanbiao Tu ◽  
Ji Tao ◽  
Zicun Liu ◽  
Fang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Detection ◽  
Tumor Targeting ◽  
Spect Imaging ◽  
Intestinal Activity ◽  
Cancer Models ◽  
Pharmacokinetic Properties ◽  
Targeting Peptide ◽  
Targeting Ability

The designed novel targeting peptide GB-6 binding to GRPR possesses more favorable pharmacokinetic properties with lower intestinal activity as well as superior tumor-targeting ability in colorectal cancer models than BBN7–14.

scholarly journals Arsenic-72, 77 as a matched pair radiopharmaceutical for imaging and radiotherapy

2018 ◽  
Author(s):  
◽  
Yutian Feng
Keyword(s):  
Physical Properties ◽  
Half Life ◽  
Operation Time ◽  
Matched Pair ◽  
Generator Column ◽  
Bombesin Receptor ◽  
Targeting Peptide ◽  
High Yields ◽  
No Carrier Added

Radiopharmaceuticals deliver radionuclides to specific target sites via the bifunctional chelate approach, where the radionuclides are chelated with a ligand and linked to a targeting biomolecule. They can be categorized as imaging or therapeutic agents based on the physical properties of the radionuclides. Matched pair radionuclides have advantages because of identical chemistry of the imaging and therapy counterparts and true matched pair radionuclides are rare (e.g., 64,67Cu, 44,47Sc, 135,131I). Radioimmunoimaging and therapy commonly use antibodies (or antibody fragments) as targeting biomolecules, and may take a few days to accumulate in tumor cells. Thus they require radionuclides with longer half-lives. Arsenic-72 ([beta]+, 26 hour half-life) and 77As ([beta]- emitter, 38.8 hour half-life) have suitable physical properties as a true matched pair for radioimaging and therapy. This dissertation focuses on the development of 72,77As matched pair for potential PET imaging and radiotherapy. ... The production and separation of no carrier added (nca) 72,77As will be discussed in Chapter 2. No carrier added 77As separation was improved based on the reported method by decreasing the operation time and increasing capacity based on reported method.[1] The parameters for a 72Se/72As generator were evaluated and nca 72Se was produced via the 70Ge([alpha], 2n)72Se nuclear reaction, separated and loaded onto a generator column. Further evaluations are underway. Radiochemistry of nca 72,77As will be discussed in Chapters 3 and 4 since two chelating approaches were evaluated. The aryl dithiol approach incorporates an aryl ring to nca radioarsenic and complexes it with dithiol ligands. After various modifications and optimizations, radiolabeling nca 72,77As affording dithioarylarsines were accomplished in high yields. The trithiol approach complexes nca 72,77As with a trithiol chelate. Its in vivo stability was evaluated by conjugating the trithiol chelate to a Bombesin receptor targeting peptide and investigating its biodistribution in normal mice. An improved trithiol chelate was proposed and synthesized based on the high in vivo stability but poor targeting efficacy of the initial trithiol complex.

scholarly journals Application of tumor-targeting peptide-decorated polypeptide nanoparticles with doxorubicin to treat osteosarcoma

Drug Delivery ◽  
2020 ◽  
Vol 27 (1) ◽  
pp. 1704-1717
Author(s):  
Renna Qiu ◽  
Denghua Sun ◽  
Yuzhuo Bai ◽  
Jiannan Li ◽  
Lizhe Wang
Keyword(s):  
Tumor Targeting ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide

Tumor-Targeting Peptide for Redox-Responsive Pt Prodrug and Gene Codelivery and Synergistic Cancer Chemotherapy

2019 ◽  
Vol 2 (4) ◽  
pp. 1420-1426 ◽  
Author(s):  
Yaxuan Bai ◽  
Zeyu Li ◽  
Liping Liu ◽  
Tiedong Sun ◽  
Xiaocheng Fan ◽  
...  
Keyword(s):  
Cancer Chemotherapy ◽  
Tumor Targeting ◽  
Redox Responsive ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide

Stiffness of targeted layer-by-layer nanoparticles impacts elimination half-life, tumor accumulation, and tumor penetration

2021 ◽  
Vol 118 (42) ◽  
pp. e2104826118
Author(s):  
Stephanie M. Kong ◽  
Daniel F. Costa ◽  
Anna Jagielska ◽  
Krystyn J. Van Vliet ◽  
Paula T. Hammond
Keyword(s):  
Drug Delivery ◽  
Half Life ◽  
Tumor Targeting ◽  
Layer By Layer ◽  
Elimination Half Life ◽  
Tumor Penetration ◽  
Anticancer Drug Delivery ◽  
Elimination Half ◽  
Tumor Accumulation

Nanoparticle (NP) stiffness has been shown to significantly impact circulation time and biodistribution in anticancer drug delivery. In particular, the relationship between particle stiffness and tumor accumulation and penetration in vivo is an important phenomenon to consider in optimizing NP-mediated tumor delivery. Layer-by-layer (LbL) NPs represent a promising class of multifunctional nanoscale drug delivery carriers. However, there has been no demonstration of the versatility of LbL systems in coating systems with different stiffnesses, and little is known about the potential role of LbL NP stiffness in modulating in vivo particle trafficking, although NP modulus has been recently studied for its impact on pharmacokinetics. LbL nanotechnology enables NPs to be functionalized with uniform coatings possessing molecular tumor-targeting properties, independent of the NP core stiffness. Here, we report that the stiffness of LbL NPs is directly influenced by the mechanical properties of its underlying liposomal core, enabling the modulation and optimization of LbL NP stiffness while preserving LbL NP outer layer tumor-targeting and stealth properties. We demonstrate that the stiffness of LbL NPs has a direct impact on NP pharmacokinetics, organ and tumor accumulation, and tumor penetration—with compliant LbL NPs having longer elimination half-life, higher tumor accumulation, and higher tumor penetration. Our findings underscore the importance of NP stiffness as a design parameter in enhancing the delivery of LbL NP formulations.

Abstract 5518: Bladder tumor-targeting peptide-mediated anti-tumor activity of a pro-apoptotic peptide

2010 ◽  
Author(s):  
Hyun-Kyung Jung ◽  
Mi-Kyung Kwak ◽  
Eun-Ju Lee ◽  
Ji Woong Son ◽  
Rang-Woon Park ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Bladder Tumor ◽  
Targeting Peptide ◽  
Tumor Targeting Peptide ◽  
Anti Tumor Activity
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