Therapeutic nanoconjugates and uses thereof

A kind of use and therapeutic agent technology, applied in drug delivery, fusion polypeptide, antibody mimic/scaffold, etc., can solve the problems of complicated antibody structure and obstacles

Pending Publication Date: 2020-05-01
巴塞罗那自治大学UAB +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the structural complexity of antibodies can be a cumbersome hurdle in terms of cost and synthesis

Method used

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  • Therapeutic nanoconjugates and uses thereof
  • Therapeutic nanoconjugates and uses thereof
  • Therapeutic nanoconjugates and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0456] Example 1: Physicochemical characterization of HS-oligo-FdU

[0457] Functionalized pentameric FdU-HEG-SH was quantified by absorbance at 260 nm and confirmed by MALDI mass spectrometry (MALDI-TOF), resulting in a MW of 1976.2, expected MW of 1974.0. The control pentanucleotide (free oligo-FdU) characterized by mass spectrometry (MALDI-TOF) obtained a MW of 1476.5, expected MW: 1478.1.

Embodiment 2

[0458] Example 2: Physicochemical Characterization of T22-GFP-H6-FdU Nanoconjugate and Determination of Drug to Nanoparticle Ratio

[0459] Analysis of the conjugated product by MALDI-TOFF spectroscopy identified the figure 2 The indicated MW peaks correspond to one or two molecules of FdU pentaoligonucleotides bound to nanoparticles. The size of T22-GFP-H6-FdU determined by dynamic light scattering was 14.6 + 0.14, compared to the size of control T22-GFP-H6 nanoparticles of 13.4 + 0.11, which is consistent with the size determined by transmission electron microscopy unanimous. The molecular weight of T22-GFP-H6 nanoparticles determined by SEC-MALS was 477 kDa. Considering the molecular weight of the T22-GFP-H6 polypeptide is 30,691 kDa, this results in approximately 15 monomers per nanoparticle. Based on the UV spectra of T22-GFP-H6 and T22-GFP-H6-FdU nanoconjugates, for the products obtained in the T22-GFP-H6-FdU nanoconjugate synthesis reaction, the obtained drug / nano...

Embodiment 3

[0460] Example 3: A targeting CXCR4 + Development of nanoconjugate T22-GFP-H6-FdU in CRC cells

[0461] It has been previously shown that overexpression of CXCR4 (CXCR4 + ) colorectal cancer (CRC) cells have metastasis initiation capacity (MIC) [Croker, A.K. & Allan, A.L. 2008. J Cell MolMed 12, 374-390; Zhang, S.S. et al. 2012. BMC Med 10, 85 (2012)], and the inhibitory effect of CXCR4 downregulation on MIC [Murakami, T. et al. 2012. BMC Med 10, 85; Wang, T.B. et al. 2014. Int J Oncol 44, 1861-1869] identified these cells as Metastatic Stem Cells (MetSC). On this basis, the inventors generated nanoconjugates targeting CXCR4 to evaluate whether they could selectively eliminate CXCR4 + CRC cells to achieve anti-metastatic effect. figure 1 , 2 The structural and physicochemical characterization of this new T22-GFP-H6-FdU nanoconjugate is described in and 4a–c. The conjugate contains T22 (a ligand targeting the CXCR4 receptor), green fluorescent protein (allowing its in v...

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Abstract

The present invention relates to nanostructured conjugates, more specifically to nanostructured fusion proteins suitable for the selective delivery of their conjugated therapeutic agents to specific cell and tissue types. It also relates to nanoparticles comprising such nanostructured proteins and the therapeutic uses thereof.

Description

technical field [0001] The present invention relates to the field of nanostructured protein materials, and more particularly relates to fusion proteins carrying therapeutic agents that can be used for treatment. Background technique [0002] Systemic administration of drugs in the form of nanoconjugates benefits from enhanced drug stability when compared to free molecules. Valuable other properties, such as cell targeting, can also be incorporated into a given hybrid composite through chemical incorporation of functional groups in nanoscale carriers, thereby benefiting from the high surface area / volume ratio of nanomaterials . When administered systemically, the resulting drug-loaded conjugates, ranging in size from about 8 to 100 nm, escape renal filtration without accumulation in the lung or other highly vascularized organs. This fact, combined with appropriate physicochemical properties of the material, may lead to prolonged circulation times and drug exposure to target...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14A61K49/18
CPCA61K49/146A61K49/1821C07K14/4702C07K2319/30
Inventor A·P·维拉维德科拉莱斯E·威克斯格梅兹U·尤祖艾塔艾洛尔扎R·玛古艾斯巴法伊M·V·塞斯佩德斯纳瓦罗I·卡萨诺瓦里加特
Owner 巴塞罗那自治大学UAB
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