Dataset Information

CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

ABSTRACT: Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.

SUBMITTER: Liang S

PROVIDER: S-EPMC4493535 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

Liang Shujing S Li Chao C Zhang Chunlei C Chen Yunsheng Y Xu Liang L Bao Chenchen C Wang Xiaoyong X Liu Gang G Zhang Fengchun F Cui Daxiang D

Theranostics 20150601 9

Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon n ...[more]

PMID: 26155313

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Project description:Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells have an unsettled capacity to uptake, retain, release, and re-uptake gold nanoparticles, thus offering enormous versatility for research. In this work, we have studied such cell capabilities for nanoparticle trafficking and its impact on the effect of photothermal treatments. As our model system, we chose uveal (eye) melanoma cells, since laser-assisted eye surgery is routinely used to treat glaucoma and cataracts, or vision correction in refractive surgery. As nanostructure, we selected gold nanostars (Au NSs) due to their high photothermal efficiency at the near-infrared (NIR) region of the electromagnetic spectrum. We first investigated the photothermal effect on the basis of the dilution of Au NSs induced by cell division. Using this approach, we obtained high PPTT efficiency after several cell division cycles at an initial low Au NS concentration (pM regime). Subsequently, we evaluated the photothermal effect on account of cell division upon mixing Au NS-loaded and non-loaded cells. Upon such mixing, we observed trafficking of Au NSs between loaded and non-loaded cells, thus achieving effective PPTT after several division cycles under low irradiation conditions (below the maximum permissible exposure threshold of skin). Our study reveals the ability of uveal melanoma cells to release and re-uptake Au NSs that maintain their plasmonic photothermal properties throughout several cell division cycles and re-uptake. This approach may be readily extrapolated to real tissue and even to treat in situ the eye tumor itself. We believe that our method can potentially be used as co-therapy to disperse plasmonic gold nanostructures across affected tissues, thus increasing the effectiveness of classic PPTT.

Project description:BackgroundApplied nanomaterials in targeted drug delivery have received increased attention due to tangible advantages, including enhanced cell adhesion and internalization, controlled targeted release, convenient detection in the body, enhanced biodegradation, etc. Furthermore, conjugation of the biologically active ingredients with the drug-containing nanocarriers (nanobioconjugates) has realized impressive opportunities in targeted therapy. Among diverse nanostructures, halloysite nanotubes (NHTs) with a rolled multilayer structure offer great possibilities for drug encapsulation and controlled release. The presence of a strong hydrogen bond network between the rolled HNT layers enables the controlled release of the encapsulated drug molecules through the modulation of hydrogen bonding either in acidic conditions or at higher temperatures. The latter can be conveniently achieved through the photothermal effect via the incorporation of plasmonic nanoparticles.ResultsThe developed nanotherapeutic integrated natural halloysite nanotubes (HNTs) as a carrier; gold nanoparticles (AuNPs) for selective release; docetaxel (DTX) as a cytotoxic anticancer agent; human IgG1 sortilin 2D8-E3 monoclonal antibody (SORT) for selective targeting; and 3-chloropropyltrimethoxysilane as a linker for antibody attachment that also enhances the hydrophobicity of DTX@HNT/Au-SORT and minimizes DTX leaching in body's internal environment. HNTs efficiently store DTX at room temperature and release it at higher temperatures via disruption of interlayer hydrogen bonding. The role of the physical expansion and disruption of the interlayer hydrogen bonding in HNTs for the controlled DTX release has been studied by dynamic light scattering (DLS), electron microscopy (EM), and differential scanning calorimetry (DSC) at different pH conditions. HNT interlayer bond disruption has been confirmed to take place at a much lower temperature (44 °C) at low pH vs. 88 °C, at neutral pH thus enabling the effective drug release by DTX@HNT/Au-SORT through plasmonic photothermal therapy (PPTT) by light interaction with localized plasmon resonance (LSPR) of AuNPs incorporated into the HNT pores.ConclusionsSelective ovarian tumor targeting was accomplished, demonstrating practical efficiency of the designed nanocomposite therapeutic, DTX@HNT/Au-SORT. The antitumor activity of DTX@HNT/Au-SORT (apoptosis of 90 ± 0.3%) was confirmed by in vitro experiments using a caov-4 (ATCC HTB76) cell line (sortilin expression > 70%) that was successfully targeted by the sortilin 2D8-E3 mAb, tagged on the DTX@HNT/Au.

Dataset Information

CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

Publications

CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

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