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Methods and related compositions for the treatment of cancer

A composition and cancer technology, applied in the medical field, can solve problems such as undeveloped complete and effective cancer treatment

Inactive Publication Date: 2018-07-17
IMMIX A DIV OF CARLTON INTL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Despite billions of dollars spent on cancer research, no complete and effective cancer treatment has been developed

Method used

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  • Methods and related compositions for the treatment of cancer
  • Methods and related compositions for the treatment of cancer
  • Methods and related compositions for the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Material

[0044] 1,2-Distearoyl-sn-glyceroyl-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PEG-PE) was from Avanti Polar Lipids (Alabaster, AL, USA) . pNP-PEG 3400 - pNP was purchased from Laysan Bio (Arab, AL). Curcumin (CUR), vitamin E and triethylamine (TEA) were purchased from Sigma (St. Louis, MO, USA). Doxorubicin hydrochloride (DOX) was from LC Laboratories (Wobum, MA). Accumax was from Innovative Cell Technologies, Inc. (San Diego, CA). CellTiter-Glo Luminescent Cell Viability Assay Kit was from Promega (Fitchburg, WI). All other reagents were of analytical grade. DOX free base was obtained by incubating DOX HCl (0.5 mg / ml in methanol) overnight with a 5-fold molar excess of TEA. pNP-PEG 3400 -PE is synthesized in-house.

Embodiment 2

[0046] Micellar preparation

[0047] Preparation of DOX and / or CUR drug-loaded mixed micelles by thin film hydration method. Add CUR (1 mg / ml in 0.1% acetic acid-methanol) and / or DOX free base (0.5 mg / ml in methanol) to PEG in chloroform 2000 -PE solution. Initial drug amounts were adjusted after formulation optimization studies to obtain a CUR:DOX ratio of 32 (w / w). The organic solvent was removed by rotary evaporation and a thin film of the drug / micelle-forming material mixture was formed. The membrane was further dried overnight in a freeze dryer to remove any organic solvent residues (Freezone 4.5 Freeze Dry System, Labconco, Kansas City, MO). Drug-loaded micelles were formed by resuspending the membrane in phosphate-buffered saline (PBS) pH 7.2 to a final concentration of micelle-forming material in all formulations of 5 mM. The micellar formulation was dialyzed against PBS pH 7.2 for 1 hour to remove excess TEA. Excess unincorporated drug was separated by filtrati...

Embodiment 3

[0050] Cytotoxicity of GLUT-1 scFv-modified micelles on ovarian cancer cell lines

[0051] For cytotoxicity assessment, A2780 human ovarian carcinoma (ATCC) and its doxorubicin resistant derivative A2780 / Adr (ECACC) were used. A2780 cells were cultured in RPMI medium supplemented with 10% FBS and 1% penicillin-streptomycin. Drug-resistant ovarian cancer cells were grown in the same medium with the addition of 100 nM DOX.

[0052] Cells were seeded in 96-well plates at a density of 3000 cells / well or 5,000 cells / well for the 48 or 24 hour treatment groups, respectively. Cells were treated with free drug or micellar formulations containing 40 μM CUR and 0.8 μM DOX in serum-complete RPMI medium. Cells were incubated consecutively for 24h and 48h in the consecutive treatment groups. Additionally, in another treatment protocol, cells were incubated with drug / micelle for 4 hours, then washed and incubated for a further 44 hours. At the end of the treatment time, the wells were...

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Abstract

Disclosed herein are compositions and nanoconjugates comprising a micelle construct; an antibody single chain fragment variable (scFv); a NF-kb inhibitor; and a topoisomerase II inhibitor. Further disclosed herein are methods of delivering a drug molecule to a tumor site of a subject comprising: attaching the drug molecule to a targeted micelle, wherein the targeted micelle comprises a micelle construct and an antibody single chain fragment variable (scFv); and delivering the drug molecule attached to the targeted micelle to the tumor site through intracellular delivery. Also disclosed hereinare methods of treating cancer or inhibiting tumor cell growth comprising administering to a subject in need thereof, a therapeutically effective dosage of a composition comprising a micelle construct, an antibody single chain fragment variable (scFv), a NF-kb inhibitor, and a topoisomerase II inhibitor.

Description

[0001] related application [0002] This application claims the benefit of priority to US Provisional Application No. 62 / 245,813, filed October 23, 2015, the entire contents of which are incorporated herein by reference. technical field [0003] The present disclosure relates to the field of medicine, and more particularly to the treatment of cancer. Background technique [0004] Despite billions of dollars spent on cancer research, no complete and effective cancer treatment has yet been developed. This is partly because tumor cells can be formed from a variety of cell types that arise and mutate differently as the cells proliferate. This diversity, in turn, is what makes cancer treatment so difficult, as populations of cancerous cells can easily include mutant varieties that happen to be resistant to whatever individual treatment or chemotherapeutic drug is administered. The small number of resistant cancer cells provides a strong selective advantage over other cells, and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K9/107A61K45/06C12N15/113
CPCA61K39/395A61K9/0019A61K45/06A61K9/1075A61K47/6849C07K16/28A61K2039/505A61K2039/55C07K2317/622A61P35/00A61K47/6909A61K31/12A61K31/704
Inventor I·拉奇曼
Owner IMMIX A DIV OF CARLTON INTL
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