NANO co-delivery of quercetin and alantolactone promotes Anti-tumor response through synergistic immunogenic cell death for microsatellite-stable colorectal cancer

A technology of inulin and immune cells, used in antitumor drugs, drug delivery, emulsion delivery, etc.

Pending Publication Date: 2022-02-11
THE UNIV OF NORTH CAROLINA AT CHAPEL HILL
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Problems solved by technology

Unfortunately for colorectal cancer patients, approximately 95% of the patient population does not respond to PD-1 / PD-L1 blockade therapy

Method used

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  • NANO co-delivery of quercetin and alantolactone promotes Anti-tumor response through synergistic immunogenic cell death for microsatellite-stable colorectal cancer
  • NANO co-delivery of quercetin and alantolactone promotes Anti-tumor response through synergistic immunogenic cell death for microsatellite-stable colorectal cancer
  • NANO co-delivery of quercetin and alantolactone promotes Anti-tumor response through synergistic immunogenic cell death for microsatellite-stable colorectal cancer

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Embodiment 1

[0067] Nanoscale co-delivery of quercetin and inulin against microsatellite-stable colorectal cancer promoting antitumor response via synergistic immunogenic cell death

[0068] 1.1 Overview

[0069] Microsatellite stable colorectal cancer (CRC) is known to be resistant to immunotherapy. The combination of quercetin (Q) and inulin (A) was found to induce synergistic immunogenic cell death (ICD) at a molar ratio of 1:4 (Q:A). To achieve proportional loading and delivery, micellar delivery of Q and A (QA-M) with high encapsulation efficiency and optimal ratio of drug loading was developed. QA-M achieved prolonged blood circulation and enhanced tumor accumulation for both drugs. More importantly, QA-M retained the desired drug ratio in tumors (molar ratio of Q to A = 1:4) at 2 and 4 hours after intravenous injection of synergistic immunotherapy. Treatment by QA-M significantly inhibited tumor growth in murine orthotopic CRC when compared to the combination of PBS and free drug...

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Abstract

Disclosed are micellar formulations comprising a synergistic combination of quercetin and alantolactone and their use for treating a cancer, including microsatellite-stable colorectal cancer (CRC), which otherwise is resistant to immunotherapy. The combination of quercetin and alantolactone was found to induce synergistic immunogenic cell death (ICD) at synergistic ratiometric micellar loadings.

Description

[0001] Federally funded research or development [0002] This invention was made with government support under Grant No. CA198999 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0003] Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, affecting both women and men. It is the third leading cause of death in the United States. Surgical resection, chemotherapy (eg, CapeOX, FOLFOX, or FOLFIRI) and radiation therapy are standard clinical treatments. However, these regimens are not effective for advanced disease, as the high recurrence rate after surgery is still troublesome. In 2017, more than 95,520 new cases of colon cancer and approximately 40,000 new cases of rectal cancer were reported in the United States alone. Although colonoscopy and other screening and preventive measures have improved survival, fewer than 40% of CRCs can be diagnosed at the localized stage. The fiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K31/07A61P35/00
CPCA61P35/00A61K31/352A61K31/343A61K9/107A61K47/22A61K47/24A61K9/0019A61K2300/00A61K9/1075A61K31/365A61K47/10
Inventor 力夫·黄张婧申丽玫
Owner THE UNIV OF NORTH CAROLINA AT CHAPEL HILL
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