Devices, systems, and methods for excavating cancer cells 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2012019049 A1 2012-02-09 [WO201219049] / 2012-02-09
申请号/申请日
2011WO-US46653 / 2011-08-04
发明人
BELLAMKONDA RAVI V;JAIN ANJANA;
申请人
GEORGIA TECH RESEARCH;
主分类号
IPC分类号
A01N-043/02A01N-043/38A61F-002/00A61K-009/00A61K-031/405
摘要
(WO201219049) Methods, devices, and systems are provided for guiding tumor movement, particularly in vivo for treatment of patients.  The method may include implanting into a tissue site where tumor cells are present a device having one or more surface structures or substrates, such as aligned nanofibers, which provide physical guidance cues for directing the migration of the tumor cells from the first tissue location to a selected second location, for tumor cell extraction or death.  The devices and systems may include a cytotoxic agent for contacting tumor cells migrated via the substrate.  All or a portion of the at least one substrate may include one or more biochemical cues, such as a coating of laminin or another protein, which may be provided in a concentration gradient to facilitate uni -directional tumor cell migration.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2010US-61370630 2010-08-04
主权利要求
(WO201219049) Claims 1. An implantable system for promoting tumor ceil migration for cell removal or death, the system comprising: at least one substrate having a surface configured, to provide cues for directing tumor cell migration along the substrate surface, the at least one substrate comprising a plurality of aligned na.nofibe.rs; and at least one cytotoxic agent for contacting tumor cells migrated via the at least one substrate. 2. The system of claim 1, wherein the plurality of aligned nanofibers form a tubular construct, 3. The system of claim 1 , wherein the plurality of aligned nanofibers are di sposed in a tubular construct, 4. The system of claim 3, wherein the tubular construct comprises an annular tube formed from a po!ycaproiactone, a polyurethane, or a combination thereof. 5. The system of claim L wherein the at ieast one cytotoxic agent is tethered or conjugated to at least a portion of the plurality of aligned nanofibers. 6. The system of claim 1, wherein the at least one cytotoxic agent is tethered or conjugated to a polymeric sink material. 7. The system of claim 6, wherein the polymeric sink material comprises a hydrogel . 8. The system of claim L wherein the cytotoxic agent comprises eyclopamine, honokioi, furegreiate, doxorubicin, or a combination thereof, 9. The system of claim 15wherein all or a portion of the at least one substrate comprises one or more biochemical cues to facilitate uni -directional tumor cell migration, 10. The system of claim L wherein the plurality of nanoiibers comprises a coating selected from the group consisting of extracellular matrix proteins, growth factors, cytokines, peptides, and combinations thereof, 1 1 . The system of claim 10, wherein the coating is disposed uniformly along the length of the plurality of aligned nanofibers. 12. The system of claim 10, wherein the coating is disposed in a concentration gradient along the length of the plurality of aligned nanoiibers from a first end of the plurality of aligned nanofibers to a second end of the plurality of aligned nanofibers, the second end being distal to the first end. 13. The system of claim 12, wherein the concentration gradient is effective to promote unidirectional migration of tumor ceils. 14. The system of claim 1 2, wherein the concentration gradient is effective to promote bidirectional migration of non-tumor cells. 15. The system of claim 1 , wherein the nanoiibers comprise a synthetic polymer. 16. The system of any one of claims 9 to 15, wherein the nanofiber films comprise a coating of myelin or a basement membrane protein. 1 7. The system of claim 1 6, wherein the nanofiber films comprise a !aminin coating. 18. The system of claim i . wherein the nanofibers have a diameter in the range of about 400 nm to about 800 urn . 19. The system of claim 1 , wherein the plurality of nanofibers are in the form of a nanofiber film having a. thickness in the range of 5 microns to 20 microns. 20. The system of any one of claim 1 to 19, wherein the plurality of aligned nanofibers are synthetic polymeric fibers having a diameter from 600 n.m to 800 nm, which are coated with an extracellular matrix protein having a concentration gradient along the length of the fibers, 21 . The system of claim 20, wherein the cytotoxic agent comprises collagen hydroge! eovalently coupled to an apoptotic triggering agent. 22. The system of claim 21 , wherein the hydroge! is at least partially encased in a cell- imperm cable pouch. 23. An implantable device for promoting tumor ceil migration for ceM removal or death, the device comprising: at least one film having a surface configured to provide cues for directing tumor ceil migration along the substrate surface, wherein the surface comprises a coating material gradient to effect uni -directional or bi -direct) on growth of ce!is across the surface. 24. The device of claim 23, further comprising a cytotoxic agent positioned for contacting tumor cells migrated via the surface. 30. A. method for guiding tumor movement in vivo, comprising: implanting into a tissue site where tumor cells are present a device having one or more surface structures which provide physical guidance cues for directing the migration of the tumor ceils from the first tissue location to a selected second location. 31 The method of claim 30, wherein the surface structure comprises nanofibers or grooves The method of claim 30 or 31 , further comprising applying another guidance means at the tissue implantation site, wherein the guidance means comprises an electric field, one or more biochemical cue, or ceil seeding, and works in combination with the physical guidance cues of the surface structure to direct migration of the tumor cells to the selected second location. The method of claim 30 or 31 , wherein the surface structure comprises a plurality of aligned nanofibers having a diameter from 400 am to 800 nm, which are coated with an extracellular matrix protein. The method of any one of claims 30 to 33, wherein the tumor cells comprise Medulloblastoma ceils or malignant glioma cells A method for treating a patient comprising: implanting at a tissue site in the patient a device comprising a substrate having a surface configured to provide cues for directing tumor cell migration along the substrate siiiface, the substrate comprising a plurality of aligned nanofibers; and subsequently killing or removing tumor cells that have migrated along the substrate surface. The method of claim 35, wherein the tissue site comprises a tumor or a void of a resected tumor. The method of claim 35, further comprising contacting tumor cells thai have migrated along at least a portion of the substrate with a cytotoxic agent. 'The method of claim 37, wherein the cytotoxic agent is part of the implanted device. The method of claim any one of claims 35 to 38, wherein tumor cells are relocated from a first region to a second region from a primary tumor via the implantable device before the tumor cells are killed or removed.
法律状态
(WO201219049) LEGAL DETAILS FOR WO2012019049  Actual or expected expiration date=2014-02-04    Legal state=DEAD    Status=LAPSED     Event publication date=2011-08-04  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2011046653  Application date=2011-08-04  Standardized application number=2011WO-US46653     Event publication date=2012-02-09  Event code=WO/A1  Event type=Examination events  Published application with search report  Publication country=WO  Publication number=WO2012019049  Publication stage Code=A1  Publication date=2012-02-09  Standardized publication number=WO201219049     Event publication date=2014-02-04  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE AU2011285639  Actual or expected expiration date=2031-08-04    Legal state=ALIVE    Status=GRANTED   Corresponding cc:  Designated or member state=AU Corresponding appl: AU2011285639  Application date in the designated or member state=2011-08-04   Application number in the designated or member state=2011AU-0285639 Corresponding cc:  Designated or member state=AU Corresponding pat: AU2011285639  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2013-02-21   Publication number in the designated or member state=AU2011285639    Event publication date=2013-02-21  Event code=WO/ENP  Event type=Entry into national phase  Entry into the national phase in: Corresponding cc:  Designated or member state=AU     Event publication date=2015-04-16  Event code=AU/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=AU  LEGAL DETAILS FOR DESIGNATED STATE CA2807483  Actual or expected expiration date=2031-08-04    Legal state=ALIVE    Status=PENDING   Corresponding cc:  Designated or member state=CA Corresponding appl: CA2807483  Application date in the designated or member state=2011-08-04   Application number in the designated or member state=2011CA-2807483 Corresponding cc:  Designated or member state=CA Corresponding pat: CA2807483  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2012-02-09   Publication number in the designated or member state=CA2807483    Event publication date=2013-02-04  Event code=WO/ENP  Event type=Entry into national phase  Entry into the national phase in: Corresponding cc:  Designated or member state=CA  LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2013-02-04    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2013-02-04  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE  LEGAL DETAILS FOR DESIGNATED STATE JP  Actual or expected expiration date=2031-08-04    Legal state=ALIVE    Status=PENDING   Corresponding cc:  Designated or member state=JP Corresponding appl: JP2013523347    Event publication date=2013-01-31  Event code=WO/ENP  Event type=Entry into national phase  Entry into the national phase in: Corresponding cc:  Designated or member state=JP     Event publication date=2016-03-30  Event code=JP/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=JP  LEGAL DETAILS FOR DESIGNATED STATE US2013172846  Actual or expected expiration date=2031-08-04    Legal state=ALIVE    Status=PENDING   Corresponding cc:  Designated or member state=US Corresponding appl: US13814009  Application date in the designated or member state=2011-08-04   Application number in the designated or member state=2011US-13814009 Corresponding cc:  Designated or member state=US Corresponding pat: US2013172846  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2013-07-04   Publication number in the designated or member state=US20130172846    Event publication date=2013-02-28  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=US
专利类型码
A1
国别省市代码
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