Aptamer-conjugated upconversion nanoprobes assisted by magnetic separation for effective isolation and sensitive detection of circulating tumor cells

Fang, Shuai; Wang, Chao; Xiang, Jian; Cheng, Liang; Song, Xuejiao; Xu, Ligeng; Peng, Rui; Liu, Zhuang

doi:10.1007/s12274-014-0497-9

Cited by 63 publications

(42 citation statements)

References 36 publications

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“…Prior to the luminescent bioassay, the OA-capped Lu 6 O 5 F 8 :Eu 3+ NPs were surface-modified via ligand exchange with citrate, and then coupled with avidin following the EDC/NHS protocol 32,33. The successful conjugation of avidin to the surface of the NPs was corroborated by the appearance of amide bands in the FTIR spectrum, the increase in dynamic light scattering (DLS) size and the decrease of the zeta-potential for the NPs after surface modification (ESI Fig.…”

Section: Resultsmentioning

confidence: 99%

Sub-5 nm lanthanide-doped lutetium oxyfluoride nanoprobes for ultrasensitive detection of prostate specific antigen

Zhou

et al. 2016

Chem. Sci.

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Section: Resultsmentioning

confidence: 99%

Sub-5 nm lanthanide-doped lutetium oxyfluoride nanoprobes for ultrasensitive detection of prostate specific antigen

Zhou

et al. 2016

Chem. Sci.

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“…Molecular imaging techniques have been developed to visualize the structure of biological tissues, which is crucial for guiding oncotherapies . Upconversion nanoparticles (UCNP) are ideal fluorescent probes for upconversion luminescence (UCL) imaging because of their splendid sensitivity and depth of penetration, and lack of autofluorescence interference . NaLuF 4 nanocrystals doped with Yb 3+ and Er 3+ ions are one of the most‐studied upconversion nanomaterials .…”

Section: Introductionmentioning

confidence: 99%

Cypate‐Conjugated Porous Upconversion Nanocomposites for Programmed Delivery of Heat Shock Protein 70 Small Interfering RNA for Gene Silencing and Photothermal Ablation

Wang

Gao

Liu

et al. 2016

Adv Funct Materials

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wileyonlinelibrary.comtoxic chemicals, and especially by heat stress, thus protecting cells from hyperthermic damage. [ 8 ] Small interfering RNA (siRNA) against HSP70 (HSP70-siRNA) can inhibit HSP70 synthesis and protein levels, [ 9 ] thereby lowering the temperature required to kill cancer cells during hyperthermic treatment. That is, the therapeutic effi cacy of PTT should be enhanced by HSP70-siRNA gene silencing. [ 10 ] Molecular imaging techniques have been developed to visualize the structure of biological tissues, which is crucial for guiding oncotherapies. [ 11 ] Upconversion nanoparticles (UCNP) are ideal fl uorescent probes for upconversion luminescence (UCL) imaging [ 12 ] because of their splendid sensitivity and depth of penetration, [ 13 ] and lack of autofl uorescence interference. [ 14 ] NaLuF 4 nanocrystals doped with Yb 3+ and Er 3+ ions are one of the most-studied upconversion nanomaterials. [ 15 ] However, UCL imaging is unable to provide detailed anatomical and physiological images in vivo. In contrast, magnetic resonance imaging (MRI) is an effective non-invasive technique for in vivo imaging and 3D tomography. [ 16 ] A combination of MRI and UCL is therefore needed to combine the merits of both these imaging modalities. [ 17 ] Therefore, UCNP doped with Gd 3+ also show magnetic resonance performance making MRI possible. [ 18 ] In this study, we prepared NaLuF 4 :Gd,Yb,Er UCNP by a one-step microemulsion method, which were further linked with cypate through a hydrazide bond. Based on their UCL and magnetic properties, the obtained nanocomposites were applied as a dual-modality contrast agent for UCL and MRI to guide oncotherapy. We also attached HSP70-siRNA to the porous UCNP (UCNP-cy-siRNA). The combinational effects of gene silencing and PTT have been investigated on a small-animal model. Moreover, the poisonousness of the UCNP-cy-siRNA has also been evaluated. Results and Discussion Design Strategy and CharacterizationsNaLuF 4 -based upconversion nanoparticles (UCNP-COOH) were fi rst prepared by a modifi ed reverse microemulsion method ( Figure 1 a), using glutarate containing carboxyl groups Synergistic therapy is an accepted method of enhancing the effi cacy of cancer therapies. In this study, cypate-conjugated porous NaLuF 4 doped with Yb 3+ , Er 3+ , and Gd 3+ is synthesized and its potential for upconversion luminescence/magnetic resonance dual-modality molecular imaging for guiding oncotherapy is tested. Loading cypate-conjugated upconversion nanoparticles (UCNP-cy) with small interfering RNA gene against heat shock protein 70 (UCNP-cy-siRNA) enhances the cell damage. UCNP-cy-siRNA exhibits remarkable antitumor effi cacy in vivo as a result of the synergistic effects of gene silencing and photothermal therapy, with low drug dose and minimal side effects. This result thus provides an explicit strategy for developing next-generation multifunctional nanoplatforms for multimodal imaging-guided synergistic oncotherapy.

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“…Aptamer–UCNP‐based targeted bioimaging and photodynamic therapy have been recently developed by Yuan et al by using an aptamer‐guided G‐Quadruplex DNA carrier and NIR light. Another example came from Fang et al who utilized the aptamer‐conjugated UCNPs for effective isolation and sensitive detection of CTCs assisted by magnetic separation. Another exciting application of aptamer–UCNPs has been reported by Wu et al, in which profiling cell surface protein‐specific glycoforms was realized based on a single excitation‐dual LRET (D‐LRET) system that consists of UCNPs as a donor and Alexa Fluor 555/660 as two different fluorescence acceptors (Figure C).…”

Section: Molecular Engineering Of Aptamer‐based Nanomaterials Toward mentioning

confidence: 99%

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

Zhang

Lan

2019

Adv Healthcare Materials

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equally exciting and perhaps more challenging field of application is toward their in vivo applications, including living animals and human bodies, in diverse areas, [2] such as sensing, drug delivery, medical imaging, and cancer therapy. However, most of these nanomaterials lack selectivity toward targets of interests. Therefore, to employ these nanomaterials for a wider range of in vivo applications, various molecular engineering approaches have been employed to obtained nanomaterials functionalized with biomolecules to enable selective targeting. [3][4][5] Among these biomolecules, functional nucleic acids, or FNAs, have shown the most promise.FNAs are DNA or RNA molecules that can interact with or bind to a specific analyte, resulting in a conformational change and/or a catalytic reaction. [6] As their names suggested, ribozymes and deoxyribozymes (called DNAzyme hereafter) can act as enzymes in the presence of cofactors to catalyze various reactions, including cleavage and ligation of RNA/DNA, and phosphorylation and peroxidation of DNA. On the other hand, riboswitches and DNA aptamers are antibody-like receptors that can bind target molecules with high affinity and selectivity. Furthermore, the binding abilities of riboswitches and aptamers can be combined with the enzymatic function of ribozymes or DNAzymes to form aptazymes so that the binding of targets can inhibit or enhance the catalytic activities. These nucleic acids, including DNAzymes, aptamers, and aptazymes, are collectively known as FNAs to emphasize their functions beyond the traditional genetic storage and transformations roles for DNA and RNA. Unlike DNA and RNA inside biological systems, FNAs are isolated via a combinatorial technique known as in vitro selection, or a process also known as systematic evolution of ligands by exponential enrichment (SELEX). The discovery of new functions of nucleic acids has not only resulted in major advances in the fields of molecular biology and biochemistry, but also revolutionized sensors designs for both in vitro and in vivo applications. [7,8] Over the past decade, numerous FNA-based nanomaterials have been developed. [9][10][11][12] Among these FNA-based nanosystems, the functions of FNAs can be categorized into two types: diagnostic function and therapeutic function. For the diagnostic function, the FNAs serve either as the biorecognition ligands for direct sensing and imaging of the Recent advances in nanotechnology and engineering have generated many nanomaterials with unique physical and chemical properties. Over the past decade, numerous nanomaterials are introduced into many research areas, such as sensors for environmental monitoring, food safety, point-ofcare diagnostics, and as transducers for solar energy transfer. Meanwhile, functional nucleic acids (FNAs), including nucleic acid enzymes, aptamers, and aptazymes, have attracted major attention from the biomedical community due to their unique target recognition and catalytic properties. Benefiting from the recent progress of molecular engine...

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Aptamer-conjugated upconversion nanoprobes assisted by magnetic separation for effective isolation and sensitive detection of circulating tumor cells

Cited by 63 publications

References 36 publications

Sub-5 nm lanthanide-doped lutetium oxyfluoride nanoprobes for ultrasensitive detection of prostate specific antigen

Sub-5 nm lanthanide-doped lutetium oxyfluoride nanoprobes for ultrasensitive detection of prostate specific antigen

Cypate‐Conjugated Porous Upconversion Nanocomposites for Programmed Delivery of Heat Shock Protein 70 Small Interfering RNA for Gene Silencing and Photothermal Ablation

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

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