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Construction and application of a liver cancer-targeting drug delivery system based on core-shell gold nanocages.

ABSTRACT: In order to achieve drug targeting and controlled release, we have successfully developed a novel drug release system DOX/AuNCs-PM-HA with gold nanocages (AuNCs) as photothermal cores, thermally responsive copolymer P(NIPAM-co-Am) (PM) as the near-infrared (NIR) stimuli gatekeeper and hyaluronic acid as a targeting ligand as well as a capping agent.Cell uptake and cell viability were investigated. In vivo photoacoustic tomography imaging in H22 tumor bearing mice was analyzed for the tumor targeting effect of the nanocomplexes. Antitumor efficacy and the tissue distribution in vivo were investigated.In vitro results demonstrated that the DOX/AuNCs-PM-HA had significant anticancer activity against SMMC-7721 cells under NIR irradiation. Furthermore, in vivo photoacoustic tomography imaging of the nanocomplexes in H22 tumor bearing mice could indicate effective tumor targeting. Our studies on antitumor efficacy and the tissue distribution in vivo showed that many DOX/AuNCs-PM-HA nanocomplexes could efficiently accumulate at the tumor site so that they could inhibit the tumor growth effectively with limited side effects. The in vitro and in vivo results confirmed that the tumor-targeting and controlled-release drug system DOX/AuNCs-PM-HA with the combination of chemotherapy and photothermal therapy showed strong anti-tumor effect and would have great potential for future cancer therapy.This tumor targeting DOX/AuNCs-PM-HA nanocomplex responded not only to the external stimuli of NIR, but also the internal stimuli of hyaluronidase, providing the potential for pinpointed and multi-stimuli responsive intracellular drug release.

SUBMITTER: Ji M

PROVIDER: S-EPMC5868592 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Construction and application of a liver cancer-targeting drug delivery system based on core-shell gold nanocages.

Ji Mengfei M Qiu Xiaojing X Hou Lin L Huang Shengnan S Li Yuanmin Y Liu Yang Y Duan Shaofeng S Hu Yurong Y

International journal of nanomedicine 20180321

<h4>Background</h4>In order to achieve drug targeting and controlled release, we have successfully developed a novel drug release system DOX/AuNCs-PM-HA with gold nanocages (AuNCs) as photothermal cores, thermally responsive copolymer P(NIPAM-co-Am) (PM) as the near-infrared (NIR) stimuli gatekeeper and hyaluronic acid as a targeting ligand as well as a capping agent.<h4>Methods</h4>Cell uptake and cell viability were investigated. In vivo photoacoustic tomography imaging in H22 tumor bearing mi ...[more]

PMID: 29606870

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Project description:One of the challenges in designing a successful drug-delivery vehicle is the control over drug release. Toward this, a number of multifunctional nanoparticles with multiple triggers and complex chemistries have been developed. To achieve an efficient and maximum therapeutic effect, a trigger dependent drug-delivery system with sustained release is desirable. In this paper, we report the use of a combination of thermoresponsive gold core and polymeric shell nanoparticles that can provide a sustained, triggered release of doxorubicin, making the system more efficient compared to individual nanoparticles. The selection of the system was dependent on the best trigger applicable in biological systems and a component responsive to that trigger. Because of the best tissue penetration depth observed for radiofrequency (rf), we chose rf as a trigger. Whereas the gold nanoparticles (AuNPs) provided hyperthermia trigger on exposure to rf fields, the thermoresponsiveness was endowed by poly(N-isopropylacrylamide) (pNIPAm)-based polymer shells. AuNPs with three different compositions of shells, only pNIPAm and p(NIPAm-co-NIPMAm) with the ratio of NIPAm/N-(isopropylmethacrylamide) (NIPMAm) 1:1 (pNIPMAm50) and 1:3 (pNIPMAm75), were synthesized. We observed that the polymer coating on the AuNPs did not affect the heating efficiency of AuNPs by rf and exhibited a temperature-dependent release of the chemotherapeutic drug, doxorubicin. The nanoparticles were biocompatible, stable in biologically relevant media, and were able to show a burst as well as a sustained release, which was rf-dependent. Interestingly, we observed that when HeLa cells were treated with doxorubicin-loaded gold core-polymeric shell NPs and exposed to rf for varying times, the mixture of the two polymeric shell nanoparticles induced more cell death as compared to the cells treated with single nanoparticles, suggesting that such multi-nanoparticle systems can be more efficacious delivery systems instead of a single multicomponent system.

Dataset Information

Construction and application of a liver cancer-targeting drug delivery system based on core-shell gold nanocages.

Publications

Construction and application of a liver cancer-targeting drug delivery system based on core-shell gold nanocages.

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