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Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with ¹⁷⁷Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers.

ABSTRACT: Lipid liquid-crystalline nanoparticles (cubosomes) were used for the first time as a dual-modality drug delivery system for internal radiotherapy combined with chemotherapy. Monoolein (GMO)-based cubosomes were prepared by loading the anticancer drug, doxorubicin and a commonly used radionuclide, low-energy beta (?^-)-emitter, ¹⁷⁷Lu. The radionuclide was complexed with a long chain derivative of DOTAGA (DOTAGA-OA). The DOTAGA headgroup of the chelator was exposed to the aqueous channels of the cubosomes, while, concerning OA, the hydrophobic tail was embedded in the nonpolar region of the lipid bilayer matrix, placing the radioactive dopant in a stable manner inside the cubosome. The cubosomes containing doxorubicin and the radionuclide complex increased the cytotoxicity measured by the viability of the treated HeLa cells compared with the effect of single-drug cubosomes containing either the DOX DOTAGA-OA or DOTAGA-OA-¹⁷⁷Lu complex. Multifunctional lipidic nanoparticles encapsulating the chemotherapeutic agent together with appropriately complexed (?^-) radionuclide are proposed as a potential strategy for effective local therapy of various cancers.

SUBMITTER: Cytryniak A

PROVIDER: S-EPMC7696353 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with 177Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers.

Cytryniak Adrianna A Nazaruk Ewa E Bilewicz Renata R Górzyńska Emilia E Żelechowska-Matysiak Kinga K Walczak Rafał R Mames Adam A Bilewicz Aleksander A Majkowska-Pilip Agnieszka A

Nanomaterials (Basel, Switzerland) 20201116 11

Lipid liquid-crystalline nanoparticles (cubosomes) were used for the first time as a dual-modality drug delivery system for internal radiotherapy combined with chemotherapy. Monoolein (GMO)-based cubosomes were prepared by loading the anticancer drug, doxorubicin and a commonly used radionuclide, low-energy beta (β-)-emitter, 177Lu. The radionuclide was complexed with a long chain derivative of DOTAGA (DOTAGA-OA). The DOTAGA headgroup of the chelator was exposed to the aque ...[more]

PMID: 33207760

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Project description:BackgroundSolid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O2 production, which in turn serves as a "radiosensitizer" to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy.ResultsHuman epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O2. ZHer2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of ZHer2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization.ConclusionsThe nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics.

Dataset Information

Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with ¹⁷⁷Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers.

Publications

Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with <sup>177</sup>Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers.

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