Tumor Targeting and Imaging Using Cyclic RGD‐PEGylated Gold Nanoparticle Probes with Directly Conjugated Iodine‐125

Kim, Young-Hwa; Jeon, Jongho; Hong, Su Hyun; Rhim, Won‐Kyu; Lee, Yun Sang; Youn, Hyewon; Chung, June‐Key; Lee, Myung Chul; Lee, Dong Hoon; Kang, Keon Wook; Nam, Jwa‐Min

doi:10.1002/smll.201100927

Cited by 178 publications

(151 citation statements)

References 42 publications

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“…The human oral squamous cell carcinoma (HSC-3) cells were incubated with 2.5 nM of AuNRs for 24 h. For AuNRs@RGD, clear scattering light of AuNRs was observed, whereas AuNRs@PEG did not show high uptake compared with the AuNRs@RGD. The difference in uptake of these two types of AuNRs is due to the binding of RGD to the surface integrin that enhances the endocytosis of AuNRs (54). For further confirmation, the internalization of AuNRs was also measured by UV-Vis spectra ( Fig.…”

Section: Resultsmentioning

confidence: 93%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

162

113

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Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e., lamellipodia and filopodia-were reduced after treatment. The Western blot analysis indicates the downstream effectors of integrin were attracted toward the antimigration direction. Proteomics results indicated broad perturbations in four signaling pathways, Rho GTPases, actin, microtubule, and kinases-related pathways, which are the downstream regulators of integrins. Due to the dominant role of integrins in controlling cytoskeleton, focal adhesion, actomyosin contraction, and actin and microtubule assembly have been disrupted by targeting integrins. PPTT further enhanced the remodeling of cytoskeletal proteins and decreased migration. In summary, the ability of targeting AuNRs to cancer cell integrins and the introduction of PPTT stimulated broad regulation on the cytoskeleton, which provides the evidence for a potential medical application for controlling cancer metastasis.gold nanorods | cytoskeleton | integrin | metastasis | plasmonic photothermal therapy

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Section: Resultsmentioning

confidence: 93%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

162

113

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“…Recently, RGD-coupled dual-modality nanoparticles such as iron oxide nanoparticles with radioisotopes (4), fluorescent dye-conjugated silica nanoparticles with radioisotopes (19), and gold nanoparticles with radioisotopes (20,25) have been used for tumor-specific imaging. Dual-modality imaging with nanoparticles can provide high-spatial-resolution anatomic information and quantitative information to target concentration.…”

Section: Discussionmentioning

confidence: 99%

“…RGD peptide has been known to specifically bind to integrin a v b 3 , which is overexpressed on both tumor and vasculature in many cancer types. RGD peptidecoupled nanoparticles were extensively studied in cancerspecific targeted imaging using quantum dots (18), iron oxide nanoparticles (4,19), and UCNPs (20).…”

mentioning

confidence: 99%

RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

et al. 2012

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Multimodal nanoparticles have been extensively studied for target-specific imaging and therapy of various diseases, including cancer. In this study, radiolabeled arginine-glycine-aspartic acid (RGD)-functionalized Er 31 /Yb 31 co-doped NaGdF 4 upconversion nanophosphors (UCNPs) were synthesized and evaluated as a multimodal PET/MR/optical probe with tumor angiogenesisspecific targeting properties. Methods: A dimeric cyclic RGDyk ((cRGDyk) 2 ) peptide was conjugated to polyacrylic acid-coated NaGdF 4 :Yb 31 /Er 31 UCNPs along with polyethylene glycol molecules and was consecutively radiolabeled with 124 I. In vitro cytotoxicity testing was performed for 3 d. Upconversion luminescence imaging of (cRGDyk) 2 -UCNP was performed on U87MG cells with a laboratory-made confocal microscope. In vivo small-animal PET and clinical 3-T T1-weighted MR imaging of 124 I-labeled RGD-functionalized UCNPs was acquired with or without blocking of cyclic RGD peptide in a U87MG tumor model. Inductively coupled plasma mass spectrometry and biologic transmission electron microscopy were done to evaluate gadolinium concentration and UCNP localization, respectively. Results: Polymer-coated UCNPs and dimeric RGD-conjugated UCNPs were monodispersely synthesized, and those of hydrodynamic size were 30 6 8 nm and 32 6 9 nm, respectively. (cRGDyk) 2 -UCNPs have a low cytotoxic effect on cells. Upconversion luminescence signals of (cRGDyk) 2 -UCNP were specifically localized on the surface of U87MG cells. 124 I-c(RGDyk) 2 -UCNPs specifically accumulated in U87MG tumors (2.8 6 0.8 vs. 1.3 6 0.4 percentage injected dose per gram in the blocking experiment), and T1-weighted MR images showed significant positive contrast enhancement in U87MG tumors. Tumor localization of 124 I-c(RGDyk) 2 -UCNPs was confirmed by inductively coupled plasma mass spectrometry and biologic transmission electron microscopy analysis. Conclusion: These results suggest that 124 Ilabeled RGD-functionalized UCNPs have high specificity for a v b 3 integrin-expressing U87MG tumor cells and xenografted tumor models. Multimodal UCNPs can be used as a platform nanoparticle with multimodal imaging for cancer-specific diagnoses.

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“…Inorganic cargos that would be useful candidates for this system include ultrasmall superparamagnetic iron oxide nanoparticles, which have been used to image lymph nodes containing micrometastases in patients with prostate cancer, 55 and Aunanoparticles, which can act as highly sensitive contrast agents for single-proton emission computed tomography imaging. 56 Other studies combined magnetic resonance imaging with biological targeting 57 using gadolinium or iron oxide based nanoparticles with a fluorescent dye. These multifunctional "nanoclinic" nanoparticles consist of a thin silica shell encapsulating magnetic iron oxide and fluorescent dyes for enhanced magnetic resonance and optical imaging.…”

Section: ■ Discussionmentioning

confidence: 99%

The Packaging of Different Cargo into Enveloped Viral Nanoparticles

Fan

Tsvetkova²,

Khuong³

et al. 2012

Mol. Pharmaceutics

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Viral nanoparticles used for biomedical applications must be able to discriminate between tumor or virus-infected host cells and healthy host cells. In addition, viral nanoparticles must have the flexibility to incorporate a wide range of cargo, from inorganic metals to mRNAs to small molecules. Alphaviruses are a family of enveloped viruses for which some species are intrinsically capable of systemic tumor targeting. Alphavirus virus-like particles, or viral nanoparticles, can be generated from in vitro self-assembled core-like particles using nonviral nucleic acid. In this work, we expand on the types of cargo that can be incorporated into alphavirus core-like particles and the molecular requirements for packaging this cargo. We demonstrate that different core-like particle templates can be further enveloped to form viral nanoparticles that are capable of cell entry. We propose that alphaviruses can be selectively modified to create viral nanoparticles for biomedical applications and basic research.

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Tumor Targeting and Imaging Using Cyclic RGD‐PEGylated Gold Nanoparticle Probes with Directly Conjugated Iodine‐125

Cited by 178 publications

References 42 publications

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

The Packaging of Different Cargo into Enveloped Viral Nanoparticles

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Tumor Targeting and Imaging Using Cyclic RGD‐PEGylated Gold Nanoparticle Probes with Directly Conjugated Iodine‐125

Cited by 178 publications

References 42 publications

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

RGD Peptide–Conjugated Multimodal NaGdF4:Yb3+/Er3+ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

The Packaging of Different Cargo into Enveloped Viral Nanoparticles

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RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis