Dataset Information

A mitochondria-targeting lipid-small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model.

ABSTRACT: Hybrid lipid‒nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles. Here we developed a kind of lipid-small molecule hybrid nanoparticles (LPHNPs) for imaging and treatment in an orthotopic glioma model. LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a‒quinolinium conjugate (PQC), a mitochondria-targeting small molecule. Compared with the pure nanofiber self-assembled by PQC, LPHNPs not only preserve the comparable antiproliferative potency, but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection. Also, this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes. By integrating the advantages from liposome and PQC molecule, LPHNPs have minimal system toxicity, enhanced potency of photodynamic therapy (PDT) and visualization capacities of drug biodistribution and tumor imaging. The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma. The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.

SUBMITTER: Tang M

PROVIDER: S-EPMC9214052 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Although as a mainstay modal for cancer treatment, the clinical effect of radiotherapy (RT) does not yet meet the need of cancer patients. Developing tumour-preferential radiosensitizers or combining RT with other treatments has been acknowledged highly necessary to enhance the efficacy of RT. The present study reported a multifunctional bioactive small-molecule (designated as IR-83) simultaneously exhibiting tumour-preferential accumulation, near-infrared imaging and radio/photodynamic/photothermal therapeutic effects. IR-83 was designed and synthesized by introducing 2-nitroimidazole as a radiosensitizer into the framework of heptamethine cyanine dyes inherently with tumour-targeting and photosensitizing effects. As results, IR-83 preferentially accumulated in tumours, suppressed tumour growth and metastasis by integrating radio/photodynamic/photothermal multimodal therapies. Mechanism studies showed that IR-83 accumulated in cancer cell mitochondria, induced excessive reactive oxygen species (ROS), and generated high heat after laser irradiation. On one hand, these phenomena led to mitochondrial dysfunction and a sharp decline in oxidative phosphorylation to lessen tissue oxygen consumption. On the other hand, excessive ROS in mitochondria destroyed the balance of antioxidants and oxidative stress balance by down-regulating the intracellular antioxidant system, and subsequently sensitized ionizing radiation-generated irreversible DNA double-strand breaks. Therefore, this study presented a promising radiosensitizer and a new alternative strategy to enhance RT efficacy via mitochondria-targeting multimodal synergistic treatment. Graphical abstract Schematic illustration of a mitochondria-targeting small molecule IR-83 designed for RT/PDT/PTT trimodalsynergistic treatment. Image 1 Highlights • IR-83 is chemically synthesized via introduction of a radiosensitizing moiety into a cancer-targeting heptamethine cyanine framework..• IR-83 exhibits multifunctional bioactivities of cancer-preferential accumulation, near infrared imaging-guided multimodal treatment.• IR-83 exerts a synergistic therapeutic effect of RT/PDT/PTT by targeting cancer cell mitochondria.• Cancer radiotherapy is significantly sensitized by mitochondria-targeting delivery of a radiosensitizing moiety, PTT-triggered increase of O2 level and PDT-induced irreversible DNA double-strand breaks.

Dataset Information

A mitochondria-targeting lipid-small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets