Nanoparticles for treating prostate cancer
Inventors
MohanKumar, Sheba M. J. • MohanKumar, Puliyur S. • Chuang, Yen-jun
Assignees
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Publication Number
US-12350384-B2
Publication Date
2025-07-08
Expiration Date
Abstract
Nanoparticles and formulations for treating prostate cancer in a subject are disclosed. The nanoparticles contain a cage, such as a zeolitic imidazolate framework (“ZIF”), a surface modifying agent, a targeting ligand, and an active agent. The surface modifying ligand is attached to the outer surface of the cage and the targeting ligand is exposed to the surrounding environment. The active agent is encapsulated in the cage. The targeting ligand binds to a reproductive hormone or a receptor of a reproductive hormone. The active agents can be a ribosome inactivating protein, an apoptosis inducer, a hormone, a receptor ligand, or a nucleic acid, or a chemotherapy drug or a combination thereof, that kill and/or reduce or prevent growth or proliferation of gonadotroph cells and/or tumor cells, regulate FSH and/or LH secretion, and/or interfere with androgen production. Uses for formulations incorporating the nanoparticles for treating cancer in a subject are also disclosed.
Core Innovation
The disclosure relates to a plurality of nanoparticles for treating or ameliorating one or more symptoms associated with a GnRH- or gonadotropin-related disease or disorder. The nanoparticles comprise a cage, a surface modifying agent, a targeting ligand, and an active agent, and the cage is a zeolitic imidazolate framework (ZIF) with the active agent encapsulated in the cage.
The surface modifying agent comprises a polymer backbone and is attached to the outer surface of the cage. The targeting ligand is exposed to the surrounding environment and includes a GnRH agonist, a GnRH antagonist, a FSH receptor agonist, a FSH receptor antagonist, a LH receptor agonist, a LH receptor antagonist, or combinations thereof.
The described formulations provide effective dosage and concentration ranges in unit dosage forms and link those formulations to pharmacodynamic outcomes. In biological samples, treatment is associated with reducing biomarker levels and/or reducing mean tumor diameter versus pre-treatment.
Claims Coverage
The independent claim covers a plurality of nanoparticles for treating or ameliorating symptoms associated with a GnRH- or gonadotropin-related disease or disorder. Across the claims, the coverage defines the ZIF cage, the surface modifying agent, the targeting ligand, and treatment outcomes, with additional claims refining nanoparticle physical characteristics and composition.
ZIF-caged GnRH/gonadotropin-targeted nanoparticles
A plurality of nanoparticles for treating or ameliorating one or more symptoms associated with a GnRH- or gonadotropin-related disease or disorder, wherein the nanoparticles comprise a cage that is a zeolitic imidazolate framework (ZIF), a surface modifying agent comprising a polymer backbone attached to the outer surface of the cage, a targeting ligand selected from a GnRH agonist, a GnRH antagonist, a FSH receptor agonist, a FSH receptor antagonist, a LH receptor agonist, a LH receptor antagonist, or a combination thereof and wherein the targeting ligand is exposed to the surrounding environment, and wherein the active agent is encapsulated in the cage.
Surface density threshold for surface modifying agent
Nanoparticles wherein a surface density of the surface modifying agent on the surface of the nanoparticles is at least a defined minimum value.
Average diameter range of the nanoparticles
Nanoparticles wherein the nanoparticles have an average diameter within one of the specified diameter ranges.
ZIF metal ion selection constraints
Nanoparticles wherein the ZIF contains a metal ion selected from a listed set of metal ions.
Polyethylene glycol polymer backbone for the surface modifying agent
Nanoparticles wherein the surface modifying agent has a polyethylene glycol polymer backbone.
Reduction of GnRH- or gonadotropin-related biomarker level and/or mean tumor diameter
An effective amount of nanoparticles is administered to reduce a GnRH- or gonadotropin-related biomarker level and/or reduce the mean tumor diameter in a subject compared to before treatment.
Overall, claim coverage centers on nanoparticles that combine a ZIF cage encapsulating an active agent with an outer polymer surface modifying agent and an exposed GnRH/gonadotropin-family targeting ligand, and it further specifies reductions in biomarker levels and/or mean tumor diameter.
Stated Advantages
Treating or ameliorating symptoms associated with a GnRH- or gonadotropin-related disease or disorder.
Reducing a GnRH- or gonadotropin-related biomarker level.
Reducing the mean tumor diameter.
Presenting a targeting ligand exposed to the surrounding environment while encapsulating an active agent in a ZIF cage.
Documented Applications
Prostate cancer treatment using ZIF-caged nanoparticles with GnRH/gonadotropin-related targeting ligands, with documented outcomes including PSA biomarker reduction and/or tumor mean diameter reduction.
Other GnRH/gonadotropin-related diseases or disorders treated or ameliorated by nanoparticles that are constructed with a ZIF cage, a polymer surface modifying agent, an exposed GnRH/gonadotropin-family targeting ligand, and an encapsulated active agent.
Use of optional diagnostic or imaging dyes encapsulated in the cage for imaging or visualization.
GnRH/gonadotropin-related cancers and disorders including endometriosis, benign tumors, uterine fibroids, prostate cancer, and ovarian cancer.
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