Title:
NANOTHERAPY TARGETING RHAMM-POSITIVE TUMORS
Document Type and Number:
WIPO Patent Application WO/2021/216997
Kind Code:
A3
Abstract:
The present technology is directed to nanoparticle compositions and methods useful in treating RHAMM-positive cancers. Such nanoparticle compositions include a plurality of nanoparticles where each nanoparticle includes (i) a particle core with an outer surface; a first layer coating the outer surface of the particle core, the first layer including one or both of poly-L-lysine and poly-L-arginine and optionally including a fluorescent dye; a second layer coating the first layer, the second layer including one or more siRNA that inhibit expression of Bcl-2, inhibit expression of Bcl-xL (BCL2L1), inhibit expression of MCL1, inhibit expression of Bcl-w (BCL2L2), inhibit expression of Bcl-b (BCL2L10), and/or inhibit expression of BFL1 (BCL2A1); a third layer coating the second layer, the third layer including an apoptotic peptide and optionally including a fluorescent dye; and a fourth layer coating the third layer, the fourth layer including hyaluronic acid or a pharmaceutically acceptable salt thereof (HA); and where the plurality of nanoparticles has an intensity- weighted average diameter as determined by dynamic light scattering from about 100 nm to about 300 nm; or (ii) a particle core with an outer surface; a first layer coating the outer surface of the particle core, the first layer including an apoptotic peptide and optionally including a fluorescent dye; a second layer coating the first layer, the second layer including one or more siRNA that inhibit expression of Bcl-2, inhibit expression of Bcl-xL (BCL2L1), inhibit expression of MCL1, inhibit expression of Bcl-w (BCL2L2), inhibit expression of Bcl-b (BCL2L10), and/or inhibit expression of BFL1 (BCL2A1); a third layer coating the second layer, the third layer including one or both of poly-L-lysine and poly-L-arginine and optionally including a fluorescent dye; and a fourth layer coating the third layer, the fourth layer including hyaluronic acid or a pharmaceutically acceptable salt thereof (HA); and where the plurality of nanoparticles has an intensity-weighted average diameter as determined by dynamic light scattering from about 100 nm to about 300 nm.
Inventors:
TUNG CHING-HSUAN (US)
DU YI-CHIEH NANCY (US)
LEE SEUNG KOO (US)
CHEN XIANG (US)
DU YI-CHIEH NANCY (US)
LEE SEUNG KOO (US)
CHEN XIANG (US)
Application Number:
PCT/US2021/028834
Publication Date:
December 02, 2021
Filing Date:
April 23, 2021
Export Citation:
Assignee:
UNIV CORNELL (US)
International Classes:
A61P35/04; A61K31/726; A61K38/17; A61K47/36; A61K48/00; C07K14/705; C12N15/113; G01N33/50
Domestic Patent References:
| WO2011009624A1 | 2011-01-27 |
Other References:
LEE SEUNG KOO, LAW BENEDICT, TUNG CHING-HSUAN: "Versatile Nanodelivery Platform to Maximize siRNA Combination Therapy", MACROMOLECULAR BIOSCIENCE, WILEY-VCH VERLAG GMBH, DE, vol. 17, no. 2, 1 February 2017 (2017-02-01), DE , pages 1600294, XP055880584, ISSN: 1616-5187, DOI: 10.1002/mabi.201600294
CHOI KI YOUNG, CORREA SANTIAGO, MIN JOUHA, LI JIAHE, ROY SWETA, LACCETTI KRISTIANA H., DREADEN ERIK, KONG STEPHANIE, HEO ROUN, ROH: "Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles", ADVANCED FUNCTIONAL MATERIALS, WILEY - V C H VERLAG GMBH & CO. KGAA, DE, vol. 29, no. 20, 1 May 2019 (2019-05-01), DE , pages 1900018, XP055880586, ISSN: 1616-301X, DOI: 10.1002/adfm.201900018
ASSMANN V, ET AL: "The human hyaluron receptoer RHAMM is expressed as an intracellular protein in breast cancer cells", JOURNAL OF CELL SCIENCE, COMPANY OF BIOLOGISTS LIMITED, CAMBRIDGE, vol. 111, 1 January 1998 (1998-01-01), Cambridge , pages 1685 - 1694, XP002173591, ISSN: 0021-9533
MELE VALENTINA, SOKOL LENA, KÖLZER VIKTOR HENDRIK, PFAFF DENNIS, MURARO MANUELE GIUSEPPE, KELLER IRENE, STEFAN ZAHND, CENTENO IREN: "The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and dissemination of colorectal cancer", ONCOTARGET, vol. 8, no. 41, 19 September 2017 (2017-09-19), pages 70617 - 70629, XP055880590, DOI: 10.18632/oncotarget.19904
CHOI SOYOUNG, WANG DUNRUI, CHEN XIANG, TANG LAURA H., VERMA AKANKSHA, CHEN ZHENGMING, KIM BU JUNG, SELESNER LEIGH, ROBZYK KENNETH,: "Function and clinical relevance of RHAMM isoforms in pancreatic tumor progression", MOLECULAR CANCER, vol. 18, no. 1, 1 December 2019 (2019-12-01), XP055880591, DOI: 10.1186/s12943-019-1018-y
CHOI KI YOUNG, CORREA SANTIAGO, MIN JOUHA, LI JIAHE, ROY SWETA, LACCETTI KRISTIANA H., DREADEN ERIK, KONG STEPHANIE, HEO ROUN, ROH: "Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles", ADVANCED FUNCTIONAL MATERIALS, WILEY - V C H VERLAG GMBH & CO. KGAA, DE, vol. 29, no. 20, 1 May 2019 (2019-05-01), DE , pages 1900018, XP055880586, ISSN: 1616-301X, DOI: 10.1002/adfm.201900018
ASSMANN V, ET AL: "The human hyaluron receptoer RHAMM is expressed as an intracellular protein in breast cancer cells", JOURNAL OF CELL SCIENCE, COMPANY OF BIOLOGISTS LIMITED, CAMBRIDGE, vol. 111, 1 January 1998 (1998-01-01), Cambridge , pages 1685 - 1694, XP002173591, ISSN: 0021-9533
MELE VALENTINA, SOKOL LENA, KÖLZER VIKTOR HENDRIK, PFAFF DENNIS, MURARO MANUELE GIUSEPPE, KELLER IRENE, STEFAN ZAHND, CENTENO IREN: "The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and dissemination of colorectal cancer", ONCOTARGET, vol. 8, no. 41, 19 September 2017 (2017-09-19), pages 70617 - 70629, XP055880590, DOI: 10.18632/oncotarget.19904
CHOI SOYOUNG, WANG DUNRUI, CHEN XIANG, TANG LAURA H., VERMA AKANKSHA, CHEN ZHENGMING, KIM BU JUNG, SELESNER LEIGH, ROBZYK KENNETH,: "Function and clinical relevance of RHAMM isoforms in pancreatic tumor progression", MOLECULAR CANCER, vol. 18, no. 1, 1 December 2019 (2019-12-01), XP055880591, DOI: 10.1186/s12943-019-1018-y
Attorney, Agent or Firm:
EWING, James F. et al. (US)
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