Aptamer imaging with Cu-64 labeled AS1411: Preliminary assessment in lung cancer

Li, Junling; Zheng, Huiyuan; Bates, Paula J.; Malik, Tariq Masood; Li, Xiaofeng; Trent, John O.; Ng, Chin K.

doi:10.1016/j.nucmedbio.2013.10.008

Cited by 64 publications

(54 citation statements)

References 25 publications

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“…The widely demonstrated role of NCL in tumorigenesis suggests that inhibition of its oncogenic actions reduces tumor aggressiveness (9,13,19,24,32,34,47), and several studies have proposed NCL as an ideal target for antineoplastic therapies in different solid and hematological malignancies (9,19,25,34,37,38,41,42,48,49). Given the selective presence of NCL on cancer cells and cancer-associated endothelial cells, but not on normal cells, molecules targeting NCL might represent an effective approach for the selective delivery of drugs or toxins to tumors while minimizing side effects (25,41).…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have shown that NCL inhibition by siRNAs or anti-NCL aptamers affects cell viability, proliferation, and migration (14,19,(37)(38)(39)(40)(41)(42)(43). To assess the effects of 4LB5 on cell viability and proliferation, we performed a dose-response (0.9-240 nM) experiment using the scFv on MDA-MB-231 triple-negative breast cancer (TNBC) cells at different time points (24,48, and 72 h). As shown in Fig.…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Human anti-nucleolin recombinant immunoagent for cancer therapy

Palmieri

Richmond

Piovan

et al. 2015

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

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Nucleolin (NCL) is a nucleocytoplasmic protein involved in many biological processes, such as ribosomal assembly, rRNA processing, and mRNA stabilization. NCL also regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and aggressiveness. Interestingly, NCL is expressed on the surface of actively proliferating cancer cells, but not on their normal counterparts. Therefore, NCL is an attractive target for antineoplastic treatments. Taking advantage of phage-display technology, we engineered a fully human single-chain fragment variable, named 4LB5. This immunoagent binds NCL on the cell surface, it is translocated into the cytoplasm of target cells, and it abrogates the biogenesis of NCLdependent miRNAs. Binding of 4LB5 to NCL on the cell surface of a variety of breast cancer and hepatocellular carcinoma cell lines, but not to normal-like MCF-10a breast cells, dramatically reduces cancer cell viability and proliferation. Finally, in orthotopic breast cancer mouse models, 4LB5 administration results in a significant reduction of the tumor volume without evident side effects. In summary, here we describe, to our knowledge, the first anti-NCL single-chain fragment variable displaying antineoplastic activity against established solid tumors, which could represent the prototype of novel immunebased NCL-targeting drugs with clinical potential as diagnostic and therapeutic tools in a wide variety of human cancers.is one of the most abundant nonribosomal proteins in the nucleolus (1), first identified in ribosomal RNA processing (2). Additional studies have demonstrated that NCL is a multifunctional nucleocytoplasmic protein, involved in ribosomal assembly, chromatin decondensation, transcription, nucleo-cytoplasmic import/export, and chromatin remodeling (3, 4). NCL is frequently up-regulated in cancer and in cancerassociated endothelial cells compared with normal tissues (5, 6), where it is also present on the cell surface (7,8). Altered NCL expression and localization results in oncogenic effects, such as stabilization of AKT, Bcl-2, Bcl-XL, and IL-2 mRNAs (9-11). Moreover, surface-NCL acts as a receptor for several oncogenic ligands (12-15) and viruses (16). Recently, we reported that NCL has a critical protumorigenic function regulating the biogenesis of selected microRNAs (miRNAs), a class of noncoding single-stranded RNAs 19-22 nt in length (17) that regulate gene expression at the posttranscriptional level by targeting mRNAs in a sequence-specific manner (18). In fact, NCL enhances the maturation of specific miRNAs (including miR-21, miR-221, and miR-222) causally involved in cancer pathogenesis and resistance to several antineoplastic treatments (19-23). Our findings demonstrated that NCL modulates the biogenesis of these miRNAs at the posttranscriptional level, enhancing their maturation from pri-to premiRNAs, identifying a novel NCL-dependent oncogenic mechanism (19).Because of its oncogenic role and specific expression on cancer cells surface, NCL represents an attractive target f...

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Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Human anti-nucleolin recombinant immunoagent for cancer therapy

Palmieri

Richmond

Piovan

et al. 2015

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

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“…In our design, hybridization with a photo-cleavable complementary oligonucleotide (A 1411 /OliP) blocked the aptamer's tumor-targeting capability, which was restored when the aptamer was released by photo-triggering. Hybridization also changed the aptamer's biodistribution, possibly by two phenomena: (i) enhanced binding to tumor upon irradiation in relation to nonspecific tissue binding, and (ii) A 1411 [and some other aptamers (7)] has a configuration that protects it from nuclease digestion (42) and is reported to have very different biodistribution from other DNA molecules that undergo rapid organ uptake followed by rapid degradation and renal clearance of breakdown products (10,43,44). The stability of A 1411 is greatly diminished by hybridization in A 1411 /OliP (Fig.…”

Section: Discussionmentioning

confidence: 99%

Aptamer photoregulation in vivo

Tong

Chu

et al. 2014

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

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The in vivo application of aptamers as therapeutics could be improved by enhancing target-specific accumulation while minimizing off-target uptake. We designed a light-triggered system that permits spatiotemporal regulation of aptamer activity in vitro and in vivo. Cell binding by the aptamer was prevented by hybridizing the aptamer to a photo-labile complementary oligonucleotide. Upon irradiation at the tumor site, the aptamer was liberated, leading to prolonged intratumoral retention. The relative distribution of the aptamer to the liver and kidney was also significantly decreased, compared to that of the free aptamer.aptamer | light triggering | cancer targeting

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“…AS1411 aptamer was bound to 64 Cu and various chelators for the early detection of lung cancer based on imaging. Li et al [112] used mouse H460 tumor xenograft model to assess the in vivo characteristics of 64 Cu-bound aptamer using PET imaging at frequent intervals. The imaging study confirmed the presence of tumor, and the higher tumor contrast ratio was achieved within anhour.…”

Section: Aptamer-based Diagnosismentioning

confidence: 99%

Aptamers and Their Significant Role in Cancer Therapy and Diagnosis

Prakash

Rajamanickam

2015

Biomedicines

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Aptamers are nucleic acid/peptide molecules that can be generated by a sophisticated, well-established technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers can interact with their targets through structural recognition, as in antibodies, though with higher specificity. With this added advantage, they can be made useful for clinical applications such as targeted therapy and diagnosis. In this review, we have discussed the steps involved in SELEX process and modifications executed to attain high affinity nucleic acid aptamers. Moreover, our review also highlights the therapeutic applications of aptamer functionalized nanoparticles and nucleic acids as chemo-therapeutic agents. In addition, we have described the development of “aptasensor” in clinical diagnostic application for detecting cancer cells and the use of aptamers in different routine imaging techniques, such as Positron Emission Tomography/Computed Tomography, Ultrasound, and Magnetic Resonance Imaging.

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Aptamer imaging with Cu-64 labeled AS1411: Preliminary assessment in lung cancer

Cited by 64 publications

References 25 publications

Human anti-nucleolin recombinant immunoagent for cancer therapy

Human anti-nucleolin recombinant immunoagent for cancer therapy

Aptamer photoregulation in vivo

Aptamers and Their Significant Role in Cancer Therapy and Diagnosis

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