IP Library › Granted Patent US 12,201,643
Granted Patent B2
US 12,201,643 · App. 17/965,908 · Granted Jan 21, 2025

Mechanochemical dynamic for focal cancer treatment

Inventors: King C. Li (Urbana, IL); Gun Kim (Urbana, IL); Qiong Wu (Urbana, IL); Jeffrey S. Moore (Savoy, IL); Yun-Sheng Chen (Champaign, IL)
Assignee: The Board of Trustees of the University of Illinois
A61K31/655A61K9/06A61K31/10A61K31/327A61K47/10A61K47/34A61P35/00
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Quick Facts
Patent No.
US 12,201,643
App. No.
17/965,908
Granted
Jan 21, 2025
Kind
B2
Abstract

Provided herein are compositions and methods for mechanochemical dynamic therapy.

Claims (27)

1. A method of generating reactive oxygen species comprising contacting a composition comprising one or more azo-mechanophores covalently linked to a hydrogel matrix or biodegradable elastomer matrix wherein the one or more azo-mechanophores are present in the hydrogel matrix or biodegradable elastomer matrix at about 3.0 wt % to about 15 wt % with high intensity focused ultrasound (HIFU).

2. A method of killing cells, tissue, or tumors comprising delivering a composition comprising one or more azo-mechanophores covalently linked to a hydrogel matrix or biodegradable elastomer matrix wherein the one or more azo-mechanophores are present in the hydrogel matrix or biodegradable elastomer matrix at about 3.0 wt % to about 15 wt % to the cells, tissue, or tumors and activating the azo-mechanophores with HIFU.

3. The method of claim 2 , wherein the cells, tissue, or tumors are cancerous and are present in a mammal.

4. The method of claim 2 , wherein the cells, tissue, or tumors are present in vitro.

5. The method of claim 2 , wherein the HIFU penetrates into the cells, tissue, or tumors to a depth of more than 1 cm.

6. The method of claim 2 , wherein the HIFU delivers continuous wave ultrasound in a pulse, wherein the pulse can be delivered once, twice, or by repeated pulsing.

7. The method of claim 3 , further comprising delivering one or more additional cancer therapies to the mammal.

8. A method of killing cells, tissue, or tumors comprising delivering a composition comprising:

(i) one or more azo-mechanophores and a nanocarrier wherein the azo-mechanophores comprise about 3.0 wt % to about 15 wt % of the composition; or

(ii) one or more azo-mechanophores a nanocarrier, and one or more tumor-homing compounds, wherein the azo-mechanophores comprise about 3.0 wt % to about 15 wt % of the composition;

wherein the composition does not comprise a chemotherapeutic agent other than the one or more azo-mechanophores,

to the cells, tissue, or tumors and activating the azo-mechanophores with HIFU.

9. The method of claim 8 , wherein the cells, tissue, or tumors are cancerous and are present in a mammal.

10. The method of claim 8 , wherein the cells, tissue, or tumors are present in vitro.

11. The method of claim 8 , wherein the HIFU penetrates into the cells, tissue, or tumors to a depth of more than 1 cm.

12. The method of claim 8 , wherein the HIFU delivers continuous wave ultrasound in a pulse, wherein the pulse can be delivered once, twice, or by repeated pulsing.

13. The method of claim 3 , further comprising delivering one or more additional cancer therapies to the mammal.

14. The method of claim 1 , wherein the hydrogel matrix or biodegradable elastomer matrix has a diameter or width of about 0.5 μM to about 10 mm.

15. The method of claim 1 , wherein the hydrogel matrix comprises polydimethylsiloxane (PDMS) or polyethylene glycol (PEG).

16. A method of killing cells, tissue, or tumors comprising delivering a composition consisting of:

(i) one or more azo-mechanophores, peroxide-mechanophores, or disulfide-mechanophores and a nanocarrier wherein the azo-mechanophores comprise about 3.0 wt % to about 15 wt % of the composition; or

(ii) one or more azo-mechanophores a nanocarrier, and one or more tumor-homing compounds, wherein the azo-mechanophores comprise about 3.0 wt % to about 15 wt % of the composition;

to the cells, tissue, or tumors and activating the azo-mechanophores with HIFU.

17. The method of claim 16 , wherein the cells, tissue, or tumors are cancerous and are present in a mammal.

18. The method of claim 16 , wherein the azo-mechanophores mechanically generate free radicals when subjected to the HIFU, which are converted to reactive oxygen species.

19. The method of claim 16 , wherein the reactive oxygen species kill the cells, tissue, or tumors via oxidative cytotoxicity, apoptosis, or both.

20. The method of claim 16 , wherein the HIFU penetrates into the cells, tissue, or tumors to a depth of more than 1 cm.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2022
From: LI, KING C.; KIM, GUN; WU, QIONG; MOORE, JEFFREY S.; CHEN, YUN-SHENG
To: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS
Reel/Frame 061659/0545 →
Continuity (2)
Provisional Application 63256239 · Oct 15, 2021
Related Publication 20230119684A1 · Apr 20, 2023
References Cited (56)
US 5543158A · Gref et al. · 1996 [cited by applicant]
US 5792742A · Gold et al. · 1998 [cited by applicant]
US 6007499A · Martin · 1999 [cited by examiner]
US 8815771B2 · Chopra et al. · 2014 [cited by applicant]
US 9687553B2 · Almutairi et al. · 2017 [cited by applicant]
US 9943606B2 · Lee et al. · 2018 [cited by applicant]
US 10143660B2 · Nel et al. · 2018 [cited by applicant]
US 10343903B2 · Zink et al. · 2019 [cited by applicant]
US 10525023B2 · Jermy et al. · 2020 [cited by applicant]
US 10583199B2 · Henkin et al. · 2020 [cited by applicant]
US 10905653B2 · Wang et al. · 2021 [cited by applicant]
US 10947350B2 · Luo et al. · 2021 [cited by applicant]
US 10967003B2 · Luo et al. · 2021 [cited by applicant]
US 11096911B2 · Jermy et al. · 2021 [cited by applicant]
US 11103594B2 · Balasamy et al. · 2021 [cited by applicant]
US 20020086049A1 · Bolton et al. · 2002 [cited by applicant]
US 20060002852A1 · Saltzman et al. · 2006 [cited by applicant]
US 20060222652A1 · Sebbel et al. · 2006 [cited by applicant]
US 20060251677A1 · Bachmann et al. · 2006 [cited by applicant]
US 20070219134A1 · Ruoslahti et al. · 2007 [cited by applicant]
US 20080014143A1 · Ruoslahti et al. · 2008 [cited by applicant]
US 20080035101A1 · Hausler et al. · 2008 [cited by applicant]
US 20080145441A1 · Penades et al. · 2008 [cited by applicant]
US 20090028910A1 · Desimone et al. · 2009 [cited by applicant]
US 20090036349A1 · Ruoslahti et al. · 2009 [cited by applicant]
US 20090226525A1 · De Los Rios et al. · 2009 [cited by applicant]
US 20190076373A1 · Bencherif et al. · 2019 [cited by applicant]
US 20200121810A1 · Li et al. · 2020 [cited by applicant]
CN 111378178A · 2020 [cited by examiner]
WO 2009051837A2 · 2009 [cited by applicant]
WO 2009106999A2 · 2009 [cited by applicant]
WO 2010047839A1 · 2010 [cited by applicant]
WO WO2020186268A1 · 2020 [cited by examiner]
WO 2021005337A1 · 2021 [cited by applicant]
WO 2021108674A1 · 2021 [cited by applicant]
CN-111378178-A Machine translation (Year: 2020). [cited by examiner]
Zhang et al. Image-Guided High-Intensity Focused Ultrasound, A Novel Application for Interventional Nuclear Medicine?. J Nucl Med. 2021;62(9):1181-1188. (Year: 2021). [cited by examiner]
Zhu et al. Vinblastine-Loaded Nanoparticles with Enhanced Tumor-Targeting Efficiency and Decreasing Toxicity: Developed by One-Step Molecular Imprinting Process. Molecular Pharmaceutics 2019 16 (6), 2675-2689. (Year: 20… [cited by examiner]
Nelson et al. J. Pharm. Sci. 2006, 95, 1527. (Year: 2006). [cited by examiner]
Awad et al. Ultrasound-Responsive Nanocarriers in Cancer Treatment: A Review. ACS Pharmacol Transl Sci. 2021;4(2):589-612. (Year: 2021). [cited by examiner]
Moad et al. Azo and Peroxy Initiators. Comprehensive Polymer Science and Supplements 8 (1996): 97-121. (Year: 1996). [cited by examiner]
Bakaic et al, “Injectable Hydrogels Based on Poly(Ethylene Glycol) and Derivatives as Functional Biomaterials”, RSC Advances , vol. 5, pp. 35469-35486, Apr. 13, 2015. [cited by applicant]
Hamzah et al, “Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice”, PNAS, vol. 108, No. 17, pp. 7154-7159, Apr. 26, 2011. [cited by applicant]
International Search Report and Written Opinion of the International Searching Authority issued in International Appl. No. PCT/US2022/078098, 9 pages, dated Dec. 30, 2022. [cited by applicant]
Joyce et al, “Stage-specific vascular markers revealed by phage display in a mouse model of pancreatic islet tumorigenesis”, Cancer Cell, vol. 4, pp. 393-403, Nov. 2003. [cited by applicant]
Kim et al, “Abstract 1318: Mechanochemical dynamic therapy for focal cancer treatment”, Cancer Res, vol. 81, 13 Supplement, pp. 1318, Apr. 10, 2021. [cited by applicant]
Kim et al, “Ultrasound controlled mechanophore activation in hydrogels for cancer therapy”, PNAS, vol. 119, No. 4, 7 pages, Dec. 9, 2021. [cited by applicant]
Laakkonen et al, “A tumor-homing peptide with a targeting specificity related to lymphatic vessels”, Nature Medicine, vol. 8, No. 7, 751-755, Jul. 2002. [cited by applicant]
Laakkonen et al, “Antitumor activity of a homing peptide that targets tumor lymphatics and tumor cells”, PNAS, vol. 101, No. 25, pp. 9381-9386, Jun. 22, 2004. [cited by applicant]
Look et al, “Nanogel-based delivery of mycophenolic acid ameliorates systemic lupus erythematosus in mice”, The Journal of Clinical Investigation, 9 pages, Mar. 1, 2013. [cited by applicant]
Moghimi et al, “Long-Circulating and Target-Specific Nanoparticles: Theory to Practice”, Pharmacological Reviews, vol. 53, No. 2, pp. 283-318, (2001). [cited by applicant]
Paolicelli et al, “Surface-modified PLGA-based nanoparticles that can efficiently associate and deliver virus-like particles”, Nanomedicine, vol. 5, No. 6, pp. 843-853, (2010). [cited by applicant]
Smith et al, “Mechanochemical dynamic therapy for focal cancer treatment” AACR Poster, (2021). [cited by applicant]
Sugahara et al, “Tissue-penetrating delivery of compounds and nanoparticles into tumors”, Cancer Cell, vol. 16, No. 6, pp. 510-520, Dec. 2009. [cited by applicant]
Tong et al, “A Facile Mechanophore Functionalization of Amphipilic Block Copolymer towards Remote Ultrasound and Redox Dual Stimulus Responsiveness”, Chemical Communications, No. 27, 10 pages, (2014). [cited by applicant]
Van Rooijen et al, “Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications”, Journal of Immunological Methods, vol. 174, pp. 83-93, (1994). [cited by applicant]
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