TABLE 2.

A selection of publications citing non-clinical experiments using AS1411 conjugated to (a) nanoparticle(s). Each of these studies has an application in treatment, or detection of a disease state in humans..

Conjugate	Target Disease	Diagnostic/ Therapeutic	Notes	Source
Doxorubicin-Bovine serum albumin	Breast Adenocarcinoma	Treatment	AS1411 was attached to Doxorubicin, this conjugate was then loaded onto Bovine serum albumin. This complex localized to cells overexpressing nucleolin leading to the downregulation of anti-apoptotic protein B-cell leukemia/lymphoma 2 protein (Bcl-2) and proliferating cell nuclear antigen (PCNA). It led to the upregulation of proto-oncogenic tumor suppressor retinoblastoma protein (pRB), DNA repair protein poly ADP-ribose polymerase (PARP), and an inducer of apoptotic cell death Bcl-2-associated X protein (Bax)	Xu et al. (2018)
miR-145 - Dextran	Breast Adenocarcinoma	Treatment	AS1411 was decorated on the surface of miR-145 (tumor suppressive) conjugated thiolated dextran. This complex specifically targeted nucleolin-expressing MCF7 Breast Adenocarcinoma cells and delivered the cargo to the cytoplasm.	Tekie et al. (2018)
C8 ligand	Malignant Melanoma	Treatment	In a murine model, AS1411 conjugated with C8 ligand increased cytotoxicity in the murine melanoma B16 cell line. C8 increased the thermostability of AS1411 without affecting its G4 topology.	Lopes-Nunes et al. (2020)
Doxorubicin	Breast Adenocarcinoma	Treatment	Doxorubicin was loaded onto α-PCNA and then condensed and coated with AS1411. This complex accumulated and is internalized at the tumor site. The targeted cells showed enhanced anticancer activity compared to doxorubicin alone.	Taghdisi et al. (2020)
Polyethylene glycol-manganese oxide	Renal Carcinoma	Diagnostic	AS1411 was conjugated with polyethylene glycol-MnO for imaging with T1 weighted MRI. This complex was able to clearly visualize renal carcinoma cells in vitro.	Li et al. (2018)
Streptavidin	Wilson’s/Alzheimer’s/Diabetes Mellitus	Diagnostic	AS1411-Streptavidin conjugate was able to detect Cu++ levels of .01 µM in serum samples of healthy patients compared to those with Wilson’s, Alzheimer’s, and Diabetes Mellitus. AS1411-Streptavidin conjugate, when applied topically to the cornea, could be delivered to the nucleus and cytoplasm of corneal endothelial cells.	Bahreyni et al. (2019)
Doxorubicin-poly D,L-lactic-co-glycolic acid-poly N-vinylpyrrolidone	Lung Adenocarcinoma	Treatment	This complex was able to trigger cell death by activating apoptosis related proteins without harming normal cells in a mouse model. The mice that received the treatment significantly recovered from lung cancer compared to control.	Saravanakumar et al. (2019)
360A	In vitro drug at this time	Treatment	360A (a telomerase inhibitor) was found to be the most promising affinity ligand for both AS1411 and AS1411-N6	Miranda et al. (2021)
Gemcitabine	Non-small cell lung cancer (NSCLC)	Treatment	Gemcitabine loaded AS1411 was decorated with polyethylene glycol-poly (lactic-co-glycolic acid) nanopolymersome. This complex targeted nucleolin-overexpressing NSCLC cells and exhibited a controlled release pattern and internalization of gemcitabine.	Alibolandi et al. (2016)
Doxorubicin	Breast Adenocarcinoma	Treatment	A multifunctional composite micelle was surface loaded with AS1411 modified Pluronic F127 and beta-cyclodextrin-linked poly (ethylene glycol)-b-polyacitide. This complex increased micelle stability, doxorubicin loading ability, micelle uptake, circulation time in blood, accumulation in tumor, antitumor activity, and decreased cardiotoxicity.	Li et al. (2015)
TGN peptide modified nanoparticles (AsTNPs)	Gliomas	Treatment	A system was developed consisting of AS1411 and AsTNPs that allowed for penetration of the blood-brain-barrier and glioma targeting in microenvironmental assays.	Gao et al. (2014)
Doxorubicin-MUC1 aptamer	Breast Adenocarcinoma	Diagnostic/ Treatment	AS1411 was loaded with Doxorubicin as well as an anti-mucin short variant S1 (MUC1) protein aptamer with a fluorophore domain for real-time imaging. This complex showed lower cytotoxicity to normal liver cells than doxorubicin alone.	Liu et al. (2018)
Paclitaxel	Gliobastoma	Treatment	A nanoconjugate system comprising of AS1411-poly (l-γ-glutamyl-glutamine)-paclitaxel was developed that optimizes the solubilization of paclitaxel. In vivo models show that the cellular uptake of paclitaxel was increased, and the median survival time increased in this system compared to paclitaxel in isolation.	Luo et al. (2017)
Doxorubicin-Au nanocluster-cyclic RGD-near infrared fluorescent dye MPA	αvβ3 integrins on tumor cells	Diagnostic/ Treatment	This cyclic RGD conjugate (which binds to αvβ3 integrins), when attached to AS1411 localizes to tumor cells as both αvβ3 integrins and nucleolin are over expressed on tumor cells. The complex penetrates deep tumors and delivers doxorubicin resulting in improved anti-tumor activity in a mouse model. The infrared MPA, as well as the Au nanocluster allows for tumor imaging both in vitro and in vivo.	Chen et al. (2016)
6-mercapto-1-hexanol	Nucleolin- expressing tumor cells	Diagnostic	AS1411 was fashioned into a microcantilever and then modified with 6-mercapto-1-hexanol. When AS1411 binds nucleolin there is induced surface stress leading to a deflection that can be detected by a sensor. This system allows detection of nucleolin at a limit concentration of 1.0 nM.	Li et al. (2016)
5-Flurouracil	Basal Cell Carcinoma	Treatment	A gel formulation containing AS1411 aptamer-functionalized polymeric nanocapsules loaded with 5-Flurouracil was developed for topical use. The complex was determined to have favorable biosafety as well as increased antitumor effects compared to 5-flurouracil alone.	Rata et al. (2021)
Erlotinib	Non-Small-Cell Lung Carcinoma	Treatment	Chitosan nanoparticles were loaded with erlotinib and then decorated with AS1411 to target non-small-cell lung cancer cells in a pH dependent manor. This complex improved uptake of erlotinib and induced apoptosis through release of reactive oxidative species.	Saravanakumar et al. (2020)
Docetaxel-TGN	Gliomas	Treatment	AS1411 was conjugated with the TGN peptide to form a drug delivery system that can penetrate the endothelial monolayer and the core of tumor spheroids of gliomas. When this system is loaded with an antineoplastic agent Docetaxel, there was high distribution of tumor distribution without much off site delivery as measured by the tumor/normal brain ratio.	Tekie et al. (2018)
Dextran-Graphene Oxide-Curcumin	Mammary Carcinoma/ Breast Adenocarcinoma	Treatment	When AS1411 was conjugated on Graphene Oxide, Dextran, and Curcumin, the complex can effectively enter breast cancer tissue and exert higher cytotoxicity than Graphene Oxide-Dextran alone.	Tekie et al. (2018)
Au@luminol nanoparticles	Circulating Tumor Cells	Diagnostic	AS1411 was added to magnetic nanoparticles in a manner that allowed a hybridization chain reaction to take place. This system results in a response signal that can be sensed at concentrations as low as 3 cells/mL in whole blood samples.	Cao et al. (2020)
.9% NaCl for Solubilization	Wet Age-Related Macular Degeneration	Treatment	AS1411 was solubilized in normal saline for both intravitreal injection, and topical application in mice with wet age-related macular degeneration. Both treatment groups of mice saw a significant decrease in the amount of choroidal neovascularization.	Leaderer et al. (2015)
Rox	Nucleolin-expressing tumors in situ	Diagnostic	Rox, a fluorescent dye, is attached to AS1411 and allowed to form a G4 complex by passing through plasmonic metamaterial decorated with cDNA in a plasmon enhanced Raman scattering detection device (PERS). In the presence of nucleolin in situ, the AS1411-Rox will dissociate and the change in signal can be sensed at a limit as low as 71pM in under 10 min.	Shi et al. (2021)