Peptide targeting of quantum dots to human breast cancer cells

Haglund, Emily; Seale-Goldsmith, Mary-Margaret; Dhawan, Deepika; Stewart, Janet; Ramos‐Vara, José A.; Cooper, Carlton R.; Reece, Lisa M.; Husk, Timothy; Bergstrom, Donald A.; Knapp, Deborah W.; Leary, James F.

doi:10.1117/12.764107

Cited by 8 publications

(12 citation statements)

References 6 publications

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“…The quantum dots in this image are dramatically incorporated into the tumor tissue compared to the peritumoral injection image. 42 …”

Section: Peptide Guided Quantum Dotsmentioning

confidence: 97%

“…The LTVSPWY peptide specific Qdots were successful at targeting and entering the SkBr3 cells. 42 was injected directly into the tumor tissue. This is illustrated in Fig.…”

Section: Peptide Guided Quantum Dotsmentioning

confidence: 99%

“…Panel b: Image of tumor tissue from a peritumoral injection. Panel c: Image of tumor tissue from a tail vein injection 42. …”

mentioning

confidence: 99%

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Design of Multifunctional Nanomedical Systems

2009

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Multifunctional nanoparticles hold great promise for drug/gene delivery and simultaneous diagnostics and therapeutics ("theragnostics") including use of core materials that provide in vivo imaging and opportunities for externally modulated therapeutic interventions. Multilayered nanoparticles can act as nanomedical systems with on-board molecular programming done through the chemistry of highly specialized layers to accomplish complex and potentially decision-making tasks. The targeting process itself is a multi-step process consisting of initial cell recognition through cell surface receptors, cell entry through the membrane in a manner to prevent undesired alterations of the nanomedical system, re-targeting to the appropriate sub-region of the cell where the therapeutic package can be localized, and potentially control of that therapeutic process through feedback systems using molecular biosensors. This paper describes a bionanoengineering design process in which sophisticated nanomedical platform systems can be designed for diagnosis and treatment of disease. The feasibility of most of these subsystems has been demonstrated, but the full integration of these interacting sub-components remains a challenge for the field. Specific examples of sub-components developed for specific applications are described.

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“…The quantum dots in this image are dramatically incorporated into the tumor tissue compared to the peritumoral injection image. 42 …”

Section: Peptide Guided Quantum Dotsmentioning

confidence: 97%

“…The LTVSPWY peptide specific Qdots were successful at targeting and entering the SkBr3 cells. 42 was injected directly into the tumor tissue. This is illustrated in Fig.…”

Section: Peptide Guided Quantum Dotsmentioning

confidence: 99%

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Design of Multifunctional Nanomedical Systems

2009

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“…Visualization of nanobiosystems in vivo represents a number of challenges even to visualize fairly large groups of nanobiosystems. Peptide‐guided quantum dot nanobiosystems targeting human cells in nude mice can be visualized in tissue sections64 as shown in Figure 4. However, even these visualizations showing excellent homing of these nanobiosystems to tumors in vivo involve thousands of agglomerated peptide‐guided quantum dots per cell.…”

Section: How Do We See and Measure Nanobiosystems?mentioning

confidence: 99%

Nanobiosystems

Seale-Goldsmith

Leary

2009

WIREs Nanomed Nanobiotechnol

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'Nanobiosystems' is a relatively new term describing objects in the size range below 150 nm and having structures or functions that link to biological functions. Key features are that these nanosized objects typically self-assemble, are not capable of self-replication, and have functions that take advantage of its size. Nanobiosystems can be made entirely of biological or organic molecules that are organized into nanoparticles (e.g., liposomes, dendrimers) or be totally inorganic (with the exception of surface coatings used for biocompatibility) nanoparticles (e.g., gold, iron oxide, quantum dot nanocrystals). More complex nanobiosystems are inorganic/biologic hybrid composites that may include complex multilayered structures with targeting molecules (e.g., peptides, antibodies, aptamers), cell entry-promoting molecules (e.g., HIV-tat peptide sequence), drugs (small molecules), genes (therapeutic genes, reporter genes), and core nanomaterials (e.g., gold, quantum dot, iron oxide) that give the nanobiosystems sometimes unique detection capabilities by a variety of optical and non-optical modalities (fluorescence, surface plasmon resonance, magnetic resonance imaging).

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“…12 In another approach, Haglund et al prepared peptide-targeted fluorescent quantum dots, directly injected them into SkBr3 breast cancer tumors in athymic mice, and analyzed histological tissue sections by fluorescence microscopy. 13 In both instances, NPs can only be detected when they are present in large aggregates/agglomerates, or in other words, above the detection threshold of the fluorescence microscope, which is bound by the wavelength of light. Individual NPs are suboptical and can only be detected when they are aggregated or agglomerated in large numbers.…”

Section: Introductionmentioning

confidence: 99%

Nanobarcoding: detecting nanoparticles in biological samples using in situ polymerase chain reaction

Eustaquio¹,

Leary²

2012

IJN

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Background: Determination of the fate of nanoparticles (NPs) in a biological system, or NP biodistribution, is critical in evaluating an NP formulation for nanomedicine. Current methods to determine NP biodistribution are greatly inadequate, due to their limited detection thresholds. Herein, proof of concept of a novel method for improved NP detection based on in situ polymerase chain reaction (ISPCR), coined "nanobarcoding," is demonstrated. Methods: Nanobarcoded superparamagnetic iron oxide nanoparticles (NB-SPIONs) were characterized by dynamic light scattering, zeta potential, and hyperspectral imaging measurements. Cellular uptake of Cy5-labeled NB-SPIONs (Cy5-NB-SPIONs) was imaged by confocal microscopy. The feasibility of the nanobarcoding method was first validated by solution-phase PCR and "pseudo"-ISPCR before implementation in the model in vitro system of HeLa human cervical adenocarcinoma cells, a cell line commonly used for ISPCR-mediated detection of human papilloma virus (HPV). Results: Dynamic light-scattering measurements showed that NB conjugation stabilized SPION size in different dispersion media compared to that of its precursor, carboxylated SPIONs (COOHSPIONs), while the zeta potential became more positive after NB conjugation. Hyperspectral imaging confirmed NB conjugation and showed that the NB completely covered the SPION surface. Solution-phase PCR and pseudo-ISPCR showed that the expected amplicons were exclusively generated from the NB-SPIONs in a dose-dependent manner. Although confocal microscopy revealed minimal cellular uptake of Cy5-NB-SPIONs at 50 nM over 24 hours in individual cells, ISPCR detected definitive NB-SPION signals inside HeLa cells over large sample areas. Conclusion: Proof of concept of the nanobarcoding method has been demonstrated in in vitro systems, but the technique needs further development before its widespread use as a standardized assay.

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Peptide targeting of quantum dots to human breast cancer cells

Cited by 8 publications

References 6 publications

Design of Multifunctional Nanomedical Systems

Design of Multifunctional Nanomedical Systems

Nanobiosystems

Nanobarcoding: detecting nanoparticles in biological samples using in situ polymerase chain reaction

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