University of Georgia Research Foundation Inc

Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Shanta Dhar

Sean M Marrache

Stephen J Lippard

Omid C Farokhzad

Frank X Gu

Rakesh Pathak

Nagesh Kolishetti

Joshua Choi

Nanoparticles include a core, a hydrophilic layer around the core, and one or more mitochondrial targeting moieties, and may optionally include one or more contrast agents or one or more therapeutic agents. For effective mitochondrial targeting the nanoparticles have a diameter of about 200 nm or less or have a zeta potential of about 0 mV or more.

Nanoparticles for mitochondrial trafficking of agents

Disclosed herein are prodrugs of platinum containing anticancer agents such as cisplatin that contain an alkylating moiety. Upon administration, the prodrugs release the platinum containing anticancer agent and the alkylating agent, which can form an adduct with DNA or can protect the platinum containing agent from removal. The disclosed prodrugs can be used to treat various cancers, including cisplatin resistant cancers.

Platinum prodrugs and methods of making and using thereof

A mitochondria targeted gold nanoparticle (T-3-BP-AuNP) decorated with 3-bromopyruvate (3-BP) and delocalized lipophilic triphenylphosphonium (TPP) cations to target the mitochondrial membrane potential (&#x394;&#x3c8;m) was developed for delivery of 3-BP to cancer cell mitochondria by taking advantage of higher &#x394;&#x3c8;m in cancer cell compared to normal cells. This construct showed remarkable anticancer activity in prostate cancer cells compared to non-targeted construct NT-3-BP-AuNP and free 3-BP. Anticancer activity of T-3-BP-AuNP was further enhanced upon laser irradiation by exciting the surface plasmon resonance band of AuNP and thereby utilizing a combination of 3-BP chemotherapeutic and AuNP photothermal effects. T-3-BP-AuNPs showed markedly enhanced ability to alter cancer cell metabolism by inhibiting glycolysis and demolishing mitochondrial oxidative phosphorylation in prostate cancer cells. Our findings demonstrated that mitochondria targeted and concerted chemo-photothermal treatment of glycolytic cancer cells with a single NP may have promise as a new anticancer therapy.

Mitochondrial delivery of 3-bromopyruvate

Described is a targeted molecular scaffold for construction of a metabolic inhibitor loaded with cancer-cell specific activity and anti-tumor immunity. Incorporation of a mitochondria targeting moiety such as triphenylphosphonium cation through a biodegradable linker in allowed for mitochondria targeting of certain metabolic inhibitors like dichloroacetic acid (DCA).

Precise delivery of therapeutic agents to cell mitochondria for anti-cancer therapy

Nanoparticles include a core and one or more targeting moieties, as well as one or more contrast agents or one or more therapeutic agents. The contrast agents or therapeutic agents may be contained or embedded within the core. If the nanoparticle includes therapeutic agents, the agents are preferably released from the core at a desired rate. The core may be biodegradable and may release the agents as the core is degraded or eroded. The targeting moieties preferably extend outwardly from the core so that they are available for interaction with cellular components, which interactions will target the nanoparticles to the appropriate cells, such as apoptotic cells; organelles, such as mitochondria; or the like. The targeting moieties may be tethered to the core or components that interact with the core.

Apoptosis-targeting nanoparticles

Provides is a therapeutic technology that combines the phototoxic and immune-stimulating ability of photodynamic therapy with the widespread effectiveness of the immune system to reduce the viability of such as cancer cells and tumors. The nanoparticle compositions of the disclosure combine an immunostimulant with a photosensitizer using a nanoparticle delivery platform. For example, zinc pthalocyanine, which is a long-wavelength absorbing photosensitizer, integrated into a polymeric nanoparticle core made up of poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG). The outside surface of the core can be coated with metallic nanoparticles, which are then modified with CpG-ODN. Metastatic mouse breast carcinoma cells showed significant photocytotoxicity of the hybrid after irradiation with a 660 nm LASER light and this activity was remarkably better than either treatment alone. Treatment of mouse bone marrow derived dendritic cells with the photodynamic therapy-killed 4T1 cell lysate showed that the combination of photodynamic therapy with a synergistic immunostimulant in a single nanoparticle system resulted in an immune response suitable for the treatment of such as a metastatic cancer.

Immune-stimulating photoactive hybrid nanoparticles

The present invention provides compositions, preparations, formulations, kits, and methods useful for treating subjects in need of therapeutic protocol, including subjects having cancer or at risk of developing cancer. Some embodiments of the invention may comprise a composition comprising a first component comprising a precursor to a therapeutically active platinum agent and a precursor to a second therapeutically active agent. The therapeutically active platinum agent and the second therapeutically active agent may dissociate from each other, thereby forming a first therapeutically active platinum agent and a second therapeutically active agent. The second therapeutically active gent may affect a cellular pathway of a cancer cell and may be substantially inactive towards non-cancerous cells.

Platinum (IV) complexes for use in dual mode pharmaceutical therapy

The present invention provides compositions, preparations, formulations, kits, and methods useful for treating subjects having cancer or at risk of developing cancer. Some embodiments of the invention may comprise a composition comprising a plurality of particles comprising a platinum(IV) therapeutically active precursor.

Growing community of inventors

Athens, GA, United States of America

Shanta Dhar