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Gold nanoplatform for near-infrared light-activated radio-photothermal gas therapy in breast cancer.

ABSTRACT: Although radiotherapy is one of the most common treatments for triple-negative breast cancer (TNBC), it frequently has unsatisfactory therapeutic outcomes due to the radiation resistance of tumor tissues. Therefore, a synergistic strategy is urgently needed to increase therapeutic responses and prolong patient survival. Herein, we constructed gold nanocages (GNCs) loaded with a hyperpyrexia-sensitive nitric oxide (NO) donor (thiolate cupferron) to integrate extrinsic radiosensitization, local photothermal therapy, and near-infrared-activated NO gas therapy. The resulting nanoplatform (GNCs@NO) showed a high photothermal conversion efficiency, which induced the death of cancer cells and facilitated rapid NO release in tumor tissues. The radiosensitizing efficacy of GNCs@NO was further demonstrated in vitro and in vivo. Importantly, the released NO reacted with the reactive oxide species induced by radiotherapy to produce more toxic reactive nitrogen species, exerting a synergistic effect to improve anticancer efficacy. Thus, GNCs@NO demonstrated excellent effects as a combination therapy with few adverse effects. Our work proposes a promising nanoplatform for the radio/photothermal/gas treatment of TNBC.

SUBMITTER: Zuo S

PROVIDER: S-EPMC9853036 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Gold nanoplatform for near-infrared light-activated radio-photothermal gas therapy in breast cancer.

Zuo Shuting S Wang Zhenyu Z Zhao Liping L Wang Jing J

Frontiers in bioengineering and biotechnology 20230106

Although radiotherapy is one of the most common treatments for triple-negative breast cancer (TNBC), it frequently has unsatisfactory therapeutic outcomes due to the radiation resistance of tumor tissues. Therefore, a synergistic strategy is urgently needed to increase therapeutic responses and prolong patient survival. Herein, we constructed gold nanocages (GNCs) loaded with a hyperpyrexia-sensitive nitric oxide (NO) donor (thiolate cupferron) to integrate extrinsic radiosensitization, local ph ...[more]

PMID: 36686245

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Project description:Photodynamic therapy (PDT) is a treatment in which photoactive compounds delivered to cancerous tissues are excited with light and then transfer the absorbed energy to adjacent tissue oxygen molecules to generate toxic singlet oxygen (1O2). As 1O2 is produced only where light and photosensitizers (PSs) are combined, PDT holds promise as a minimally invasive, highly selective treatment for certain cancers. The practical application of PDT requires easily synthesized, water-soluble PSs that have low dark toxicities, high 1O2 quantum yields, and efficient absorption of 650-850 nm near-infrared (NIR) light, which deeply penetrates tissue. We recently developed a linear tetrapyrrole metal complex, Pd[DMBil1]-PEG750, that meets most of these criteria. This complex is remarkably effective as a PS for PDT against triple-negative breast cancer (TNBC) cells but, critically, it does not absorb NIR light, which is necessary to treat deeper tumors. To enable NIR activation, we synthesized a new derivative, Pd[DMBil1]-PEG5000-SH, which bears a thiol functionality that facilitates conjugation to NIR-absorbing gold nanoshells (NSs). Upon excitation with pulsed 800 nm light, NSs emit two-photon-induced photoluminescence spanning 500-700 nm, which can sensitize the attached PSs to initiate PDT. Additionally, NSs produce heat upon 800 nm irradiation, endowing the NS-PS conjugates with an auxiliary photothermal therapeutic (PTT) capability. Here, we demonstrate that NS-PS conjugates are potent mediators of NIR-activated tandem PDT/PTT against TNBC cells in vitro. We show that Pd[DMBil1]-PEG5000-SH retains the photophysical properties of the parent Pd[DMBil1] complex, and that NS-PS generate 1O2 under pulsed 800 nm irradiation, confirming activation of the PSs by photoluminescence emitted from NSs. TNBC cells readily internalize NS PS conjugates, which generate reactive oxygen species in the cells upon pulsed NIR irradiation to damage DNA and induce apoptosis. Together, these findings demonstrate that exploiting photoluminescent NSs as carriers of efficient Pd[DMBil1] PSs is an effective strategy to enable NIR light-activated tandem PDT/PTT.

Dataset Information

Gold nanoplatform for near-infrared light-activated radio-photothermal gas therapy in breast cancer.

Publications

Gold nanoplatform for near-infrared light-activated radio-photothermal gas therapy in breast cancer.

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