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Stimuli-responsive nanoparticles for biomedical applications

a biomedical and stimuli-responsive technology, applied in the direction of nanocapsules, microcapsules, capsule delivery, etc., can solve the problems of affecting the toxic and side effects of healthy tissues, and achieve the effects of high loading efficiency, excellent stability, and high stability in water

Inactive Publication Date: 2019-04-25
THE BRIGHAM & WOMEN S HOSPITAL INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a type of nanoparticle that can be used as a delivery tool for therapeutic and diagnostic agents. These nanoparticles have a stable core and a hydrophobic outer shell, which allows them to encapsulate a wide range of molecules and evade recognition by the immune system. The nanoparticles can be designed to release their cargo in response to specific stimuli, such as pH, temperature, or enzymes, in the body. This makes them ideal for targeted delivery to specific cells or tissues, minimizing toxic side effects and improving the efficacy of therapy. The nanoparticles can also be used for imaging and theranostic applications, where they can be designed to respond to the unique microenvironment of tumor tissue.

Problems solved by technology

Therefore, developing stimuli-responsive NPs that can specifically respond to tumor microenvironment will accomplish the targeted delivery of cargos to tumor sites and thus and impair the toxic and side effects to healthy tissues.
The problem with the stimuli responsive NPs is that they often to not make it to area where release is desired, being phagocytozed, undergoing enzymatic attack, or becoming physically entrapped on their way to the desired target.

Method used

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  • Stimuli-responsive nanoparticles for biomedical applications
  • Stimuli-responsive nanoparticles for biomedical applications
  • Stimuli-responsive nanoparticles for biomedical applications

Examples

Experimental program
Comparison scheme
Effect test

example 1

Responsive and Tumor-Penetrating Nanoplatform for Targeted siRNA Delivery with Robust Anti-Cancer Efficacy

Methods and Materials

Materials

[0369]Methoxyl-polyethylene glycol (Meo-PEG113-OH) and hydroxyl polyethylene glycol carboxylic acid (HO-PEG113-COOH) were purchased from JenKem Technology and used as received. Internalizing RGD (iRGD) with the sequence CRGDRGPDC (SEQ ID NO:11) was obtained from GL Biochem Ltd. 2-(Diisopropyl amino) ethyl methacrylate (DPA-MA), glycidyl methacrylate (GMA), and methyl methacrylate (MMA) were provided by Sigma-Aldrich and passed over an alumina column before use in order to remove the hydroquinone inhibitors. α-Bromoisobutyryl bromide, triethylamine (TEA), N,N,N′,N′,N′-pentamethyldiethylenetriamine (PMDETA), copper (I) bromide (CuBr), N,N′-dimethylformamide (DMF), tetraethylenepentamine (TEPA), 1,2-epoxyhexadecane, isopropyl alcohol, and dichloromethane (DCM) were acquired from Sigma-Aldrich and used directly. Lipofectamine 2000 (Lipo2K) was purchased...

example 2

Responsive and Tumor-Penetrating Nanoplatform for Targeted siRNA Delivery with Robust Anti-Cancer Efficacy

Methods and Materials

[0442]Materials

[0443]Methoxyl-polyethylene glycol (Meo-PEG113-OH) and hydroxyl polyethylene glycol carboxylic acid (HO-PEG113-COOH) were purchased from JenKem Technology and used as received. Oligoarginine (NH2-Rn—CONH2, n=6, 8, 10, 20, 30) was provided by MIT Biopolymer facility. Allyl protected S,S-2-[3-[5-amino-1-carboxypentyl]-ureido]-pentanedioic acid (ACUPA) was kindly provided by BIND Therapeutics as a gift. 2-(Diisopropyl amino) ethyl methacrylate (DPA-MA) and glycidyl methacrylate (GMA) were provided by Sigma-Aldrich and passed over an alumina column before use in order to remove the hydroquinone inhibitors. α-Bromoisobutyryl bromide, N,N′-dimethylformamide (DMF), triethylamine (TEA), N,N,N′,N′,N′-pentamethyldiethylenetriamine (PMDETA), copper (I) bromide (CuBr), tetraethylenepentamine (TEPA), isopropyl alcohol, p-toluenesulfinate tetrahydrate (PTSF...

example 3

Responsive Nanoparticles (NPs) as Nanoprobe for Cancer Diagnostics

Methods and Materials

Synthesis of Meo-PEG-Br and Br-PEG-COOH

[0507]The detailed synthesis is same as the description in Examples 1 and 2.

Synthesis of methoxyl-polyethylene glycol-b-poly (2-(diisopropylamino) ethylmethacrylate-co-glycidyl methacrylate) (Meo-PEG-b-P(DPA-co-GMA))

[0508]Meo-PEG113-b-P(DPA80-co-GMA5) copolymer was synthesized according to the same method described in Example 1.

Synthesis of Meo-PEG-b-P(DPA-co-GMA-TEPA)

[0509]Meo-PEG-b-P(DPA-co-GMA-TEPA) was synthesized according to the same method described in Example 1.

Synthesis of Meo-PEG-b-P(DPA-co-GMA-TEPA-Cy5.5)

[0510]Meo-PEG-b-P(DPA-co-GMA-TEPA) (0.2 g) and Cy5.5 NHS ester (1.5-fold molar excess relative to the TEPA repeating unit) were well dissolved in 5 mL of THF. After constantly stirring in dark for 48 h, the solution was dialyzed against deionized water and the product was collected after freeze-drying. The synthesis scheme is shown above.

Synthesis ...

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Abstract

Stimuli-responsive NPs with excellent stability, high loading efficiency, encapsulation of multiple agents, targeting to certain cells, tissues or organs of the body, can be used as delivery tools. These NPs contain a hydrophobic inner core and hydrophilic outer shell, which endows them with high stability and the ability to load therapeutic agents with high encapsulation efficiency. The NPs are preferably formed from amphiphilic stimulus-responsive polymers or a mixture of amphiphilic and hydrophobic polymers or compounds, at least one type of which is stimuli-responsive. These NPs can be made so that their cargo is released primarily within target certain cells, tissues or organs of the body, upon exposure to endogenous or exogenous stimuli. The rate of release can be controlled so that it may be a burst, sustained, delayed, or a combination thereof. The NPs have utility as research tools or for clinical applications including diagnostics, therapeutics, or combination of both.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of and priority to U.S. Provisional Application No. 62 / 317,033, filed Apr. 1, 2016, which is hereby incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was supported by the National Institutes of Health grants EB015419 (O.C.F), CA151884 (O.C.F.), HL127464 (O.C.F.), R00CA160350 (J.S.) and CA200900 (J.S.).FIELD OF THE INVENTION[0003]This invention is generally in the field of developing stimuli-responsive solid polymeric nanoparticles (NPs) which can be used to deliver therapeutic and diagnostic agents including nucleic acids, proteins, chemotherapeutic drugs, or other small molecules.BACKGROUND OF THE INVENTION[0004]Nanoparticles have become an important tool in many industries including healthcare. Biomedical application of NPs has introduced exciting opportunities for the improvement of disease diagnosis and treatment. In part...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K9/51A61K47/65
CPCA61K49/0054A61K49/0021A61K9/5138A61K9/5146A61K47/65A61K49/0093A61K31/711A61K9/1273A61K9/5153C08F293/005C08F2438/01A61K49/0032C08F220/286C08F220/34C08F220/325
Inventor XU, XIAODINGSHI, JINJUNFAROKHZAD, OMID C.
Owner THE BRIGHAM & WOMEN S HOSPITAL INC
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