Targeted PH sensitive liposomes
Inventors
Gordon, Leo I. • Kim, Dong-Hyun • Yang, Shuo • Park, Wooram • Sim, Taehoon
Assignees
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Publication Number
US-12599677-B2
Publication Date
2026-04-14
Expiration Date
Abstract
Disclosed herein are synthetic nanoparticles, pharmaceutical compositions, kits, or methods for treating and/or preventing cancer. In some embodiments, the synthetic nanoparticles and/or pharmaceutical compositions comprises a pH sensitive liposome, an apolipoprotein, and andrographolide or derivative thereof. In some embodiments, the synthetic nanoparticles are delivered to a subject for treatment of cancer. In some embodiments, the cancer is T-cell lymphoma or B-cell lymphoma.
Core Innovation
The invention provides a synthetic nanoparticle that includes a pH sensitive liposome comprising a lipid layer, where an apolipoprotein is in contact with the lipid layer and a drug having a low water solubility is encapsulated within the liposome. The pH sensitive liposome comprises octadecylamine-p(API-L-ASP)10 (pH-ADT).
The pH-sensitive liposome design is used to deliver low-water-solubility andrographolide and/or a derivative thereof and to target pH-disordered microenvironments, including lymphoma (B-cell and T-cell) and other pH-disordered microenvironments. The apolipoprotein-based targeting is described in connection with scavenger receptor B-1 (SR-B1) via apolipoproteins such as Apo-A1.
The disclosure also includes configurations and properties of the synthetic nanoparticle that support pH-triggered behavior, including optional nanostructure cores and defined particle property ranges such as particle size and zeta potential in solutions at pH 7.4 and pH 6.5. The disclosure further describes pH-dependent drug release and related biological effects, including endosomal disruption/escape and apoptosis in cancer-cell contexts.
Claims Coverage
The independent claim covers a synthetic nanoparticle with a pH-sensitive liposome including a pH-sensitive lipid specified as octadecylamine-p(API-L-ASP)10, an apolipoprotein in contact with the lipid layer, and a low-water-solubility drug encapsulated within the liposome. The provided claims also add particle size and zeta potential refinements, additional liposome components, andrographolide as the encapsulated drug, and method coverage directed to apoptosis of live cancer cells.
P H-sensitive liposome with apolipoprotein and low-water-solubility drug
A pH sensitive liposome comprising a lipid layer comprising at least one pH sensitive lipid; an apolipoprotein in contact with the lipid layer; and a drug having a low water solubility encapsulated within the liposome.
Specific pH-ADT lipid composition
The pH sensitive liposome comprises octadecylamine-p(API-L-ASP)10 (pH-ADT).
Apoptosis-inducing treatment via effective contact with cancer cells
The method contacts the cancer cells with the synthetic nanoparticle in an effective amount to induce apoptosis, thereby reducing live cancer cell numbers.
Particle size limitation
The synthetic nanoparticle has a largest cross-sectional dimension of less than or equal to 1000 nanometers (nm).
Zeta potential range at pH 7.4
The synthetic nanoparticle has a zeta potential between about 0 and about -5, about -4 and about -1, or about -21 and about -23 in a solution of about pH 7.4.
Additional liposome-forming lipids
The pH-sensitive liposome further comprises egg-phosphatidylcholine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000), DSPE-PEG-Cy5, and/or a combination thereof.
Andrographolide as the encapsulated drug
The synthetic nanoparticle contains the drug andrographolide and/or a derivative thereof.
Overall, the claims coverage centers on a synthetic nanoparticle with a pH-sensitive liposome using the specified pH-ADT lipid and an apolipoprotein positioned in contact with the lipid layer, encapsulating a low-water-solubility drug including andrographolide and/or derivatives. Dependent refinements further define particle size and zeta potential at pH 7.4, optionally add specified liposome components, and include method coverage for inducing apoptosis by contacting cancer cells with the nanoparticle.
Stated Advantages
Induces apoptosis in cancer-cell contexts, thereby reducing live cancer cell numbers.
Provides pH-dependent drug release responsive to acidic conditions associated with pH-disordered microenvironments.
Documented Applications
Targeting lymphoma (B-cell and T-cell) and other pH-disordered microenvironments using the apolipoprotein-mediated, pH-sensitive synthetic nanoparticle.
Treating cancer cells by inducing apoptosis and reducing live cancer cell numbers.
Documented comparisons in lymphoma cell lines and CLL patient-derived cells, including increased apoptosis/cytotoxicity versus controls.
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