Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy

Chen, Dan; Li, Bowen; Cai, Songhua; Wang, Peng; Peng, Shuwen; Sheng, Yuanzhi; He, Yuanyuan; Gu, Yueqing; Chen, Haiyan

doi:10.1016/j.biomaterials.2016.05.017

Cited by 123 publications

(115 citation statements)

References 42 publications

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“…To overcome the drawback of single‐targeting delivery systems, dual ligand conjugated nanoparticles were developed. For example, graphene oxide (nGO) modified with folic acid (FA) and cyclic RGD peptide (cRGD) was developed for tumor targeting . We can choose two different ligands, one for tumor cell membrane‐targeting, and the other for membrane penetration to delivery drugs to the perinuclear.…”

Section: Introductionmentioning

confidence: 99%

A Smart Responsive Dual Aptamers‐Targeted Bubble‐Generating Nanosystem for Cancer Triplex Therapy and Ultrasound Imaging

Zhao

Zhou

et al. 2017

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The absence of targeted, single treatment methods produces low therapeutic value for treating cancers. To increase the accumulation of drugs in tumors and improve the treatment effectiveness, near-infrared 808 nm photothermal responsive dual aptamers-targeted docetaxel (DTX)-containing nanoparticles is proposed. In this system, DTX and NH HCO are loaded in thermosensitive liposomes. The surface of liposomes is coated with gold nanoshells and connected with sulfydryl (SH) modified AS1411 and S2.2 aptamers. The nanosystem has good biocompatibility and uniform size (diameter about 200 nm). The drug is rapidly released, reaching a maximum amount (84%) at 4 h under 808 nm laser irradiation. The experiments conducted in vitro and in vivo demonstrate the nanosystem can synergistically inhibit tumor growth by combination of chemotherapy, photothermal therapy, and biological therapy. Dual ligand functionalization significantly increases cellular uptake on breast cancer cell line (MCF-7) cells and achieves ultrasound imaging (USI) at tumor site. The results indicate that this drug delivery system is a promising theranostic agent involving light-thermal response at tumor sites, dual ligand targeted triplex therapy, and USI.

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Section: Introductionmentioning

confidence: 99%

A Smart Responsive Dual Aptamers‐Targeted Bubble‐Generating Nanosystem for Cancer Triplex Therapy and Ultrasound Imaging

Zhao

Zhou

et al. 2017

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“…In addition to its selectivity, the possibility to effectively reverse the functional effect of the complex using an antisense of the polyvalent aptamers was demonstrated. AuNP-based dual targeting was also obtained by designing a novel nano-platform containing cyclic Arg-Gly-Asp (cRGD) that is specific for αvβ3integrins, and the AS1411 aptamer [65]. The complex was further functionalized with near infrared fluorescence dye or DOX, to produce a dual-targeting NIR fluorescent probe or pro-drug with a favorable tumor-targeting both in vitro and in vivo.…”

Section: Aptamer-nanoparticles Systemsmentioning

confidence: 99%

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

2016

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The selective delivery of drugs in a cell- or tissue-specific manner represents the main challenge for medical research; in order to reduce the occurrence of unwanted off-target effects. In this regard, nucleic acid aptamers have emerged as an attractive class of carrier molecules due to their ability to bind with high affinity to specific ligands; their high chemical flexibility; as well as tissue penetration capability. To date, different aptamer-drug systems and aptamer–nanoparticles systems, in which nanoparticles function together with aptamers for the targeted delivery, have been successfully developed for a wide range of therapeutics, including toxins; peptides; chemotherapeutics and oligonucleotides. Therefore, aptamer-mediated drug delivery represents a powerful tool for the safe and effective treatment of different human pathologies, including cancer; neurological diseases; immunological diseases and so on. In this review, we will summarize recent progress in the field of aptamer-mediated drug delivery and we will discuss the advantages, the achieved objectives and the challenges to be still addressed in the near future, in order to improve the effectiveness of therapies.

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“…NCL targeting ligands, including the oligonucleotide aptamer AS-1411 [32] and the F3 peptide [33], have been used to direct antisense oligonucleotides [34], nanoparticles [35–39], and liposomes [40, 41] to tumor blood vessels for imaging [35, 36, 38, 39] and therapeutic applications [34, 37–39, 41]. AS-1411 is a 29-mer oligonucleotide aptamer (molecular weight (MW) ~14,500) and F3 is a 34-mer peptide (MW ~3500).…”

Section: Introductionmentioning

confidence: 99%

In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

et al. 2017

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Nucleolin (NCL) plays an important role in tumor vascular development. An increased endothelial expression level of NCL has been related to cancer aggressiveness and prognosis and has been detected clinically in advanced tumors. Here, with a peptide targeted to NCL (F3 peptide), we created an NCL-targeted microbubble (MB) and compared the performance of F3-conjugated MBs with non-targeted (NT) MBs both in vitro and in vivo. In an in vitro study, F3-conjugated MBs bound 433 times more than NT MBs to an NCL-expressing cell line, while pretreating cells with 0.5 mM free F3 peptide reduced the binding of F3-conjugated MBs by 84%, n=4, p<0.001. We then set out to create a method to extract both the tumor wash-in and wash-out kinetics and tumor accumulation following a single injection of targeted MBs. In order to accomplish this, a series of ultrasound frames (a clip) was recorded at the time of injection and subsequent time points. Each pixel within this clip was analyzed for the minimum intensity projection (MinIP) and average intensity projection (AvgIP). We found that the MinIP robustly demonstrates enhanced accumulation of F3-conjugated MBs over the range of tumor diameters evaluated here (2 to 8 mm), and the difference between the AvgIP and the MinIP quantifies inflow and kinetics. The inflow and clearance were similar for unbound F3-conjugated MBs, control (non-targeted) and scrambled control agents. Targeted agent accumulation was confirmed by a high amplitude pulse and by a two-dimensional Fourier Transform technique. In summary, F3-conjugated MBs provide a new imaging agent for ultrasound molecular imaging of cancer vasculature, and we have validated metrics to assess performance using low mechanical index strategies that have potential for use in human molecular imaging studies.

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Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy

Cited by 123 publications

References 42 publications

A Smart Responsive Dual Aptamers‐Targeted Bubble‐Generating Nanosystem for Cancer Triplex Therapy and Ultrasound Imaging

A Smart Responsive Dual Aptamers‐Targeted Bubble‐Generating Nanosystem for Cancer Triplex Therapy and Ultrasound Imaging

Aptamer-Mediated Targeted Delivery of Therapeutics: An Update

In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

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