Embodiments of the present disclosure provide for hydrogels, methods of making hydrogels, methods of using hydrogels, methods of isolating, trapping, attracting, and/or killing cancer cells, and the like.
Drawings
Claims39
A random coil polypeptide polymer substrate hydrogel, comprising:
a random coil polypeptide polymer substrate including:
a Q block including a Q substrate including at least one glutamine group;
a K block including a K substrate including at least one lysine group;
and
a biocompatibility substrate or a biocompatibility substance,
wherein the Q block and the K block are crosslinked to one another via one or more glutamine groups of the Q block and one or more of the lysine groups of the K block;
wherein one or both of the Q block and the K block include a random coil protein substrate, wherein one or both of the Q block and the K block include a bioactive substrate, wherein a cancerous human cell has an affinity for the bioactive substrate.
4 more elements
A hydrogel comprising:
a reaction product including a biocompatibility substrate, wherein the reaction product is formed from a Q block and a K block in the presence of an enzymatic cross-linking agent, wherein a Q block includes a Q substrate including at least one glutamine group and the K block includes a K substrate including at least one lysine group, wherein one or both of the Q block and the K block include a random coil substrate;
wherein the Q block and the K block are cross-linked to one another via one or more glutamine groups of the Q block and one or more of the lysine groups of the K block, wherein the reaction product is a random coil polypeptide polymer substrate, wherein the biocompatibility substrate is selected from the group consisting of:
a poly(ethylene glycol) (PEG), a poly(vinyl alcohol) (PVA), a poly(acrylic acid) (PAA), a poly(propylene fumarate-co-ethylene glycol) (P(PF-co-EG)), a polyacrylamide, a polypeptide, a poly-N-substituted glycine oligomer or polymer (polypeptoid), hyaluronic acid (HA), an alginate, a chitosan, an agarose, a collagen, a silk, an elastin, a fibrin, a gelatin, a dextran, a combination thereof, and a derivative of each of these;
wherein the Q substrate is selected from the group consisting of:
SEQ ID NOs. 1-5, QQ, QQQ, and a combination thereof;
wherein the K substrate is selected from the group consisting of:
(SEQ ID NO. 6)nG, (SEQ ID NO. 7)nG, (SEQ ID NO. 8)nG, and a combination thereof, where n is 1 to 600;
and wherein the random coil substrate is selected from the group consisting of:
SEQ ID NOs. 6-8, (SEQ ID NO. 1)2, (SEQ ID NO. 2)3, and a combination thereof.
6 more elements
A random coil polypeptide polymer substrate hydrogel, comprising:
a random coil polypeptide polymer substrate including:
a Q block including a Q substrate including at least one glutamine group;
a K block including a K substrate including at least one lysine group;
and
a biocompatibility substrate or a biocompatibility substance,
wherein the Q block and the K block are crosslinked to one another via one or more glutamine groups of the Q block and one or more of the lysine groups of the K block;
wherein one or both of the Q block and the K block include a random coil protein substrate.
4 more elements
A hydrogel comprising:
a reaction product including a biocompatibility substrate, wherein the reaction product is formed from a Q block and a K block in the presence of an enzymatic cross-linking agent, wherein a Q block includes a Q substrate including at least one glutamine group and the K block includes a K substrate including at least one lysine group, wherein one or both of the Q block and the K block include a random coil substrate;
wherein the Q block and the K block are cross-linked to one another via one or more glutamine groups of the Q block and one or more of the lysine groups of the K block,
wherein the reaction product is a random coil polypeptide polymer substrate.
#Current cancer treatment options typically involve a combination of invasive surgery to excise cancerous tissue that can be detected, followed by radiotherapy and chemotherapy. The latter two treatments, while causing substantial tissue damage and illness, are deployed as tools to kill any cancer cells that remain and which either could not be detected or could not be removed. These methods are not very effective in reducing cancer recurrence, especially in patients whose cancers are detected at late stages. If we consider cases in which cancer is detected at an early stage, so that cancer cells have not yet been disseminated from the primary site, surgery may leave residual cancer cells in the periphery of the tumor site and/or can cause tumor fragmentation, which can increase the chances of recurrence. In additional, natural wound healing processes initiated at the surgical site flood the area with growth factors, and this can stimulate enhanced proliferation or migration of any residual cancer cells (which is one reason that radiation is generally applied locally, after surgery). In breast cancer, if tumor formation recurs, it tends to be in the lungs or in lymph nodes near the breast tissue. The major source of this type of metastasis is residual cancerous cells left by invasive tumor removal procedures, such as a lumpectomy, even with the application of combined radio- and chemotherapy treatments, or by recurring cancerous cells at the primary tumor site, which then become metastatic, by migrating into lymphatic channels or blood vessels. Besides the common case of cancer recurrence, patients who are treated according to the most common disease management protocol often suffer from a variety of severe side effects of current treatments. Chemotherapeutics and gamma irradiation treatments often lack specificity and damage healthy tissue in the process, which leads to discomfort or pain that exhausts patients, depresses their immune systems, and begin tissue remodeling processes that have long-term negative health consequences (e.g., edema, scarring, or lung damage eventually leading to impaired breathing).
#At this time, there is a clear need to provide alternative approaches to the treatment of cancer and other diseases involving the dissemination of cells with pathological characteristics.
#Embodiments of the present disclosure provide for hydrogel, methods of making hydrogels, methods of using hydrogels, methods of isolating pathogenic cells such as cancer cells, and the like.
Brief description of the drawings1 figure
#Many aspects of the disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.
#FIGS. 1A-1E illustrates an in vitro invasion assay. FIG. 1A illustrates a transwell chamber with a filter membrane on the bottom, coated with a layer of 5% (wt) protein hydrogel. FIGS. 1B to 1C) illustrates a cell attachment observed 12 hours after seeding. FIGS. 1D to 1E illustrate that after 5 days of cell seeding the filter membranes beneath the hydrogels were fixed and stained. FIGS. 1B and 1D are MRC5 cancer cells. FIGS. 1C and 1E are PC3 cancer cells.
Detailed description14,275 words
#Before the present disclosure is described in greater detail, it is to be understood that this disclosure is not limited to particular embodiments described, and as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.
#Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.
#Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, the preferred methods and materials are now described.
Application
12/624,043Filed 23 Nov 2009 · us provisional application
Priority
22 Nov 2008
Published
US 2010/0159008 A124 Jun 2010
Granted
27 Jan 2015
Term ends
3 Sep 2032Estimated · howhide20 years from earliest known nonprovisional domestic filing plus recorded patent term adjustment, including 1,015 days of adjustment. Maintenance-fee lapses, terminal disclaimers and statutory extensions have not been checked. The continuity chain may be incomplete; this is not an enforceability determination.