Carrier-free curcumin nanoparticle for EGFR positive cancer therapy
Inventors
Assignees
Publication Number
US-11904022-B2
Publication Date
2024-02-20
Expiration Date
2041-03-26
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Abstract
A carrier-free nanoparticle based on the self-assembly of curcumin-erlotinib conjugate (EPC) that exhibits stronger cell killing, better anti-migration effects, and anti-invasion effects for pancreatic cancer cells than the combination of free curcumin and erlotinib.
Core Innovation
The invention provides a carrier-free nanoparticle based on the self-assembly of a curcumin-erlotinib conjugate (EPC) for cancer therapy. The nanoparticle is prepared by synthesizing PEG-modified erlotinib, conjugating it with curcumin, dissolving the conjugate in acetone, and then adding it dropwise to deionized water to form self-assembled nanoparticles. These nanoparticles exhibit stronger cell killing, enhanced anti-migration, and anti-invasion effects in pancreatic cancer cells (BxPC-3) compared to the use of free curcumin and erlotinib together.
The disclosed nanoparticles effectively accumulate in tumor tissues in a xenograft tumor mouse model, resulting in significant inhibition of pancreatic tumor growth and marked extension of survival time in treated mice. Importantly, the nanoparticles do not lead to systemic toxicity in major organs. The uniformity and scalable nature of the curcumin-erlotinib conjugate further reduce challenges associated with carrier-based nanoparticles such as non-uniform carrier structure and unpredictable fate.
The problem addressed by the invention is the limitations associated with conventional nanoparticle drug delivery systems, which typically utilize a carrier and a payload. These limitations include low drug loading content, premature drug release, non-standardized or non-uniform carrier structure, and difficulty in predicting the fate of the carrier, leading to only a few nanomedicines being FDA-approved. The carrier-free approach circumvents these issues by eliminating the need for an additional carrier and enhancing the synergistic anticancer effects of curcumin and erlotinib, particularly for EGFR positive cancers such as pancreatic cancer.
Claims Coverage
The patent contains one independent claim that focuses on the inventive method for preparing a carrier-free nanoparticle for tumor growth inhibition.
Method for preparing a carrier-free nanoparticle for tumor growth inhibition
The inventive feature comprises the following ordered steps: 1. Synthesizing PEG-modified erlotinib. 2. Conjugating the PEG-modified erlotinib with curcumin to form an erlotinib-curcumin conjugate. 3. Dissolving the erlotinib-curcumin conjugate in acetone to create a solution. 4. Adding the solution dropwise to deionized water, enabling self-assembly of at least one carrier-free nanoparticle. This method yields nanoparticles usable for inhibiting tumor growth, specifically without the use of a separate carrier.
The claim coverage centers on a specific, carrier-free nanoparticle preparation method utilizing a curcumin-erlotinib conjugate, highlighting the stepwise formation of self-assembled nanoparticles for tumor growth inhibition.
Stated Advantages
The nanoparticle exhibits stronger cell killing, better anti-migration, and anti-invasion effects for pancreatic cancer cells than the combination of free curcumin and erlotinib.
The carrier-free nanoparticle can effectively accumulate in tumor tissue in a xenograft tumor mouse model.
The EPC nanoparticle effectively reduces the growth of pancreatic tumors and extends the median survival time of tumor-bearing mice.
No systemic toxicity was detected in the major organs of mice receiving EPC treatment.
Attributed to the uniformity of the curcumin-erlotinib conjugate and ease of scaling up, the nanoparticle can be readily produced at larger scale.
Circumvents the limitations of conventional carrier-based nanoparticle systems, such as low drug loading content, premature drug release, and non-uniform carrier structure.
Documented Applications
Treatment of pancreatic cancer, specifically in EGFR positive pancreatic cancer cells and xenograft mouse models.
General application in inhibiting tumor growth by administering carrier-free nanoparticles formed from curcumin-erlotinib conjugate.
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