Aptamer-Based Probes for Cancer Diagnostics and Treatment
Abstract
:1. Introduction
2. Aptamer-Based Probes for Cancer Diagnosis
2.1. Cancer Surface Membrane Biomarkers
2.1.1. Receptors
2.1.2. Cell Adhesion Molecules
2.1.3. Cell Membrane-Associated Enzymes
2.1.4. Other Membrane-Associated Proteins
2.2. Extracellular Cancer Biomarkers
3. Aptamer-Based Cancer Therapy
3.1. Aptamer as Therapeutic Agent
3.1.1. Cancer Surface Membrane Biomarkers-Based Therapy
3.1.2. Other Biomarkers-Based Therapy
3.2. Aptamer as Delivery Agents
3.2.1. Cancer Surface Biomarkers-Targeted Delivery Therapy
3.2.2. Intracellular Targeted Therapy
4. Conclusions and Future Prospects
Aptamer Name | DNA/RNA | Target | Targeted Disease | Clinical Status | Ref. |
---|---|---|---|---|---|
Pegaptanib (PEGylated), VEap121 | RNA | VEGF165 | Age-related macular degeneration (AMD) Diabetic macular edema Diabetic retinopathy | In market | [245] |
AS1411 | DNA | Nucleolin | Acute myeloid leukemia Metastatic renal cell carcinoma | Phase II (NCT01034410) Phase II (NCT00740441) Phase I (NCT00881244) | [246] |
68Ga-Sgc8 | DNA | PTK7/ CCk-4 | Colorectal cancer | Early Phase 1 (NCT03385148) | [247] |
ARC1905 (Zimura) | RNA | C5 | Dry AMD Idiopathic polypoidal choroidal vasculopathy (IPCV) | Phase I completed, Phase II and III recruiting (NCT02686658) Zimura in Combination with Anti-VEGF Therapy in Subjects with IPCV (NCT02397954) | [149] |
E-10030 (Fovista) | DNA | PDGF | Neovascular AMD | Phase II (NCT02214628) Anti-PDGF Pegylated Aptamer with Lucentis (NCT01089517) for neovascular AMD Fovista in Combination with Lucentis as compared to Lucentis monotherapy (NCT01940900) | [248] |
REG1 anticoagulation system (RB006 and RB007) (RB006) Antidote (RB007) | RNA | Coagulation factor IXa | Acute coronary syndrome Coronary artery disease Percutaneous coronary intervention | Phase I and II completed (NCT00113997, NCT00932100, NCT01872572) | [249] |
ARC1779 | DNA | Von Willebrand factor (A1 domain) | Purpura, Thrombotic Thrombocytopenic von Willebrand disease Acute myocardial infarction | Phase II (NCT00632242) Phase II (NCT00507338) | [250] |
NU172 | DNA | Thrombin | Heart disease | Phase II (NCT00808964) | [251] |
NOX-A12 | RNA | CXCL12 | Chronic lymphocytic leukemia Multiple myeloma Colorectal cancer Pancreatic cancer | Phase II (NCT01486797) NOX-A12 in Combination with Bortezomib and Dexamethasone Phase II (NCT01521533) | [252] |
NOX-E36 | RNA | MCP-1 | Chronic Inflammatory Diseases Type 2 diabetes Mellitus Systemic Lupus Erythematosus | Phase I (NCT00976729) | [253] |
NOX-H94 (lexaptepid pegol) | RNA | Human Hepcidin | Anemia of chronic disease End-stage renal disease | Phase I and II (NCT02079896) | [254] |
ApTOLL | DNA | Toll-like receptor (TLR4) | Acute ischemic stroke Acute myocardial infarction | Phase I (NCT04742062) | [255] |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Biomarkers | Aptamer Name | Diagnosis Mechanism | DNA/RNA | Limit of Detection (LOD) | Cancer Type | Ref. |
---|---|---|---|---|---|---|
EGFR | Anti-EGFR aptamer | Aptamer/antibody based immunosensor. | DNA | 50 pg/mL | Human epidermal squamous cell carcinoma | [22] |
Anti-EGFR aptamer | Origami-paper-based graphene-modified aptasensor. | DNA | 5 pg/mL | Nonsmall-cell lung cancer | [23] | |
MinE07 | 18F-labeled RNA aptamer for PET imaging. | RNA | - | Lung cancer | [24] | |
VEGFR2 | Anti-VEGFR2 aptamer | Aptamers-modified magnetic nanoparticles for MR imaging | DNA | - | Breast cancer | [27] |
HER2 | HB5 | Proximity-induced fluorescence activation of aptamers and G-rich sequences templated AgNCs. | DNA | 0.0904 fM | Breast cancer | [28] |
LC-MS/MS-based quasi-targeted proteomics strategy coupled with aptamers-triggered hybridization chain reactions. | DNA | - | Breast cancer | [29] | ||
Proximity-induced fluorescence activation of aptamer-templated AgNCs. | DNA | 220 pM | Breast cancer | [32] | ||
PTK7 | Sgc8 | 18F labeled aptamer for PET imaging. | DNA | - | Malignant melanoma | [33] |
Electrochemical aptamer-based determination by toehold-mediated strand displacement amplification on AuNPs and GOs. | DNA | 1.8 fM | Colon cancer | [34] | ||
CD4 | Anti-CD4 aptamer | Aptamers containing surfaces for capture of CD4 expressing cells. | RNA | - | HIV/AIDS | [37] |
CD30 | CD30 | Aptamer conjugated IRD800CW reporter for imaging. | RNA | - | Lymphoma | [39] |
Cyanine dye (Cy5) labeled aptamers for flow cytometry detection of CD30 -expressing cells. | RNA | 0.3 nM | Lymphoma | [40] | ||
CD63 | CD63 | Aptamer accelerated intrinsic peroxidase-like activity of g-C3N4 nanosheets for detection of exosomes. | DNA | 13.52 × 105 particles/μL | Breast cancer | [41] |
Aptamer capped single-wall carbon nanotubes based colorimetric aptasensor for detection of exosomes. | DNA | 5.2 × 102 particles/μL | Breast cancer | [42] | ||
Aptamer and G-quadruplex/hemin DNAzyme modified ECL sensor for detection of exoxomes. | DNA | 7.41 × 104 particles/mL | Breast cancer | [43] | ||
Aptamer linked dual AuNPs based sensor for detection of exosomes by surface plasmon resonance. | DNA | 5 × 103 particles/mL | Breast cancer | [44] | ||
Aptamer-based fluorescence polarization for separation of free exosomes quantification. | DNA | 500 particles/μL | Breast cancer | [45] |
Biomarkers | Aptamer Name | Diagnosis Mechanism | DNA/RNA | LOD | Cancer Type | Ref. |
---|---|---|---|---|---|---|
EpCAM | EpCAM | Aptamer-based graphene quantum dots and MoS2 nanosheets for detection of target through FRET. | DNA | 450 pM | Breast cancer | [48] |
Enzyme-free fluorescence detection of EpCAM by a combined aptamer-based recognition and toehold-aided DNA recycling amplification strategy. | DNA | 0.1 ng/mL | Breast cancer | [49] | ||
Aptamer conjugated maleimidyl magnetic nanoplatform for facile MRI. | DNA | - | Breast cancer | [50] | ||
Graphene oxide and fluorescent labeled aptamers for detection of exosomes. | DNA | 2.1 × 104 particles/µL | Colorectal cancer | [51] | ||
Aptamer modified Ti3C2 MXenes nanosheets based chemiluminescence biosensor for detection of exosomes. | DNA | 125 particles/µL | Breast cancer | [53] | ||
EpCAM and CD63 aptamer-based 3D DNA walker amplification and Exo III-assisted electrochemical ratiometric detection of exosomes. | DNA | 1.3 × 104 particles/mL | Breast cancer | [55] | ||
Aptamer-based gold nanostars for detection of EpCAM overexpressed-CTCs by RCA coupled with the hemin/G-quadruplex complex. | DNA | 1 cell/mL | Breast cancer | [56] | ||
Integrins | Aptαvβ3 | Aptamer conjugated magnetic nanoparticles for detection of integrin ανβ3 by MRI. | DNA | - | Glioblastoma | [57] |
H02 | Aptamer as probes for cyto- and histofluorescence. | RNA | - | Glioblastoma | [58] |
Biomarkers | Aptamer Name | Diagnosis Mechanism | DNA/RNA | LOD | Cancer Type | Ref. |
---|---|---|---|---|---|---|
PSMA | xPSM-A9 xPSM-A10 | Aptamer as probes and processed the ability to inhibit N-acetyl-α-inked acid dipeptidase. | RNA | 2.1 nM 11.9 nM | Prostatic cancer | [61] |
xPSM-A10 | Aptamer conjugated AuNPs for detection of target by utilizing tissue microarrays. | RNA | - | Prostatic cancer | [62] | |
A10-3.2 | Aptamer-oriented lipid nanobubbles as ultrasound contrast agent. | RNA | - | Prostatic cancer | [63] | |
A10 | Aptamer conjugated multi-walled carbon nanotubes as ultrasound contrast agent. | RNA | - | Prostatic cancer | [64] | |
RNA/peptide dual-aptamer probe based electrochemical detection. | RNA | - | Prostatic cancer | [66] | ||
MMP-9 | F3B | 99mTc labeled aptamer for ex vivo imaging slices of human brain tumors. | RNA | 20 nM | Glioblastoma | [68] |
Dual aptamer-based piezoelectric biosensor for the detection of target. | RNA | 1.2 pM | - | [69] | ||
Programmed hybridization/dehybridization of aptamers on the surface of AuNSs based photoacoustic contrast agent. | RNA | - | Breast cancer | [70] |
Biomarkers | Aptamer Name | Diagnosis Mechanism | DNA/RNA | LOD | Cancer Type | Ref. |
---|---|---|---|---|---|---|
MUC1 | MUC1 | Fluorescence aggregation assay by carbon dot-labeled antibodies and aptamers. | DNA | 2 nM | - | [74] |
Aptamer-tagged AgNCs for fluorescent imaging. | DNA | 0.05 nM | Breast cancer | [75] | ||
Four-way branch migration-based strategy for amplified aptamer detection of MUC1. | DNA | 2.8 nM | - | [76] | ||
Dual-aptamer (VEGF and MUC1 aptamers) nanoparticle-mediated signal amplification strategy for cancer cells colorimetric detection. | DNA | 10 cells/mL | Breast cancer | [77] | ||
Aptamer conjugated carbon nanospheres for electrochemical detection of target. | DNA | 40 cells/mL | Colon cancer | [78] | ||
Label free aptasensor for electrochemical detection of target by combining hemin/G-quadruplex system and RCA. | DNA | 9.54 × 102 particles/mL | Gastric cancer | [80] | ||
Nucleolin | AS1411 | Aptamer-based microcantilever biosensor for the detection of target. | DNA | 1.0 nM | - | [82] |
64Cu labeled aptamer for tumor-targeted imaging by microPET/CT. | DNA | - | Lung cancer | [83] | ||
Aptamer conjugated with HYNIC and 99mTc for thin layer chromatography. | DNA | - | Prostate cancer | [84] | ||
Cobalt-ferrite nanoparticle surrounded by fluorescent rhodamine within silica shell matrix conjugated with aptamer for multimodal cancer-targeted imaging. | DNA | - | Glioma | [85] | ||
AS1411 aptamer-based phosphorescent nanoprobe for tumor imaging. | DNA | - | Breast cancer | [86] | ||
Dual aptamer (AS1411 and CD63 aptamer) recognition-based G-quadruplex nanowires for the detection of exosomes. | DNA | 1.85 × 103 particles/mL | Cervical carcinoma | [87] | ||
MUC1 aptamer functionalized magnetic beads and AS1411 modified quantum dots based nano-bio-probes for the multimode detection of target. | DNA | 201 cells/mL 85 cells/mL | Breast cancer | [88] | ||
Sandwich-type cytosensor based on MOF and DNA tetrahedron linked dual aptamer (AS1411 and MUC1) for electrochemical detection of target. | DNA | 6 cells/mL | Breast cancer | [89] | ||
VEGF165 | VEGF165 | Bivalent aptamer-Cu nanocluster for fluorescent detection of target. | DNA | 12 pM | Colorectal cancer | [92] |
Nicking endonuclease-assisted signal amplification of a split aptamer beacon for detection of target. | DNA | 1 pM | Breast cancer | [93] | ||
AgNPs-enhanced time resolved fluorescence sensor for VEGF165 detection by using long-lived fluorescent Mn-doped ZnS QDs. | DNA | - | - | [94] | ||
Aptamer conjugated USPIO nanoparticles for MRI imaging of VEGF165-expressing tumors in vivo. | DNA | - | Liver cancer | [95] |
Biomarkers | Aptamer Name | Diagnosis Mechanism | DNA/RNA | LOD | Cancer Type | Ref. |
---|---|---|---|---|---|---|
PDGF-BB | PDGF-BB | Aptamer modified AuNPs for colorimetric detection of target. | DNA | 32 nM | - | [100] |
Aptamer-based DNA enzyme-catalyzed colorimetric reaction coupled with RCA for colorimetric detection of target. | DNA | 8.2 fM | Breast cancer | [101] | ||
AuNPs labeled and target-triggered strand displacement amplification for colorimetric detection of target. | DNA | 1.1 nM | Breast cancer | [102] | ||
Aptamer-based cascade amplification SERS method for the detection of target. | DNA | 0.42 pM | - | [103] | ||
Aptamer conjugated hydrophobic Ru (II) complex for label-free luminescent detection of target. | DNA | 0.8 pM | - | [104] | ||
Target-triggered hybridization chain reaction amplification and GO-based selective fluorescence quenching. | DNA | 1.25 pM | - | [105] | ||
Photo-induced electron transfer between aptamer-AgNCs and G-quadruplex/hemin complexes. | DNA | 1 × 10−13 M | - | [106] | ||
FRET based aptasensor using UCNPs as donor and AuNPs as acceptor for the detection of target. | DNA | 10 nM | Lymphoma | [107] | ||
The precipitates’ electrochemical aptasensing between the reaction of phosphate group in both HAP-NPs and the aptamer reacted with molybdate. | DNA | 50 fg/mL | - | [110] | ||
AFP | AFP | Target-induced aptamer switched mode for label-free fluorescent detection of target. | DNA | 1.76 nM | - | [115] |
Sandwich binding type based fluorescent aptasensor for detection of target. | DNA | 400 pM | Hepatocellular carcinoma | [116] | ||
CEA | CEA | Fluorophore-labeled aptamer-absorbed MoS2 nanosheets for detection of target. | DNA | 34 pg/mL | Gastrointestinal neoplasms | [118] |
Aptamer linking AgNCs with AuNPs for fluorescent detection of target. | DNA | 3 pg/mL | - | [119] | ||
Aptamer-based FRET sensor between NIR-CDs and AuNRs for fluorescent detection of target. | DNA | 0.02 pg/mL | Lung cancer | [121] | ||
Aptamer-based dsDNA templated copper nanoparticles for label-free fluorescent detection of target. | DNA | 6.5 pg/mL | - | [122] | ||
Exonuclease III-assisted target recycling and DNA walker amplification strategy for fluorescent detection of target. | DNA | 1.2 pg/mL | - | [123] | ||
8-OHdG | 8-OHdG | Aptamer combined with NMM fluorophore to form a fluorescent switch to detect target. | DNA | 1.19 nM | - | [126] |
Aptamer-based 3D DNA nanomachine for fluorescent detection of target. | DNA | 4 pM | - | [127] | ||
Target-triggered polyaniline deposition on aptamer-based tetrahedral DNA nanostructure for electrochemical detection of target. | DNA | 1 pM | Bladder cancer | [128] | ||
Fe3O4-aptamer magnetic nanoparticles for the detection of target by HPLC-MS. | DNA | 0.01 nM | - | [129] |
Biomarkers | Aptamer Name | Delivery Mechanism | DNA/RNA | Cancer Type | Ref. |
---|---|---|---|---|---|
PSMA | A10 | Dtxl-encapsulated nanoparticles formulated with PLGA-b-PEG copolymer and surface functionalized with aptamers. | RNA | Prostate cancer | [158] |
DNA-RNA hybrid aptamer coupled SPION to delivery DOX. | RNA | Prostate cancer | [159] | ||
Aptamers anchored nanoparticles to encapsulate docetaxel for tumor delivery | RNA | Prostate cancer | [160] | ||
Aptamers-siRNA chimera for in vivo delivery for targeted gene silencing therapy | RNA | Prostate cancer | [161] | ||
Aptamer-conjugated cationic liposomes to deliver therapeutic CRISPR/Cas9 | RNA | Prostate cancer | [162] | ||
Dual aptamer-modified gold nanostars for generating heat to induce apoptosis. | RNA | Prostate cancer | [164] | ||
DOX carried aptamer conjugated with DTX loaded PLGA-b-PEG nanoparticles for targeted chemotherapy. | RNA | Prostate cancer | [166] | ||
DOX carried aptamer conjugated with shRNA loaded PEG-PEI polyplexes for targeted chemogene therapy. | RNA | Prostate cancer | [167] | ||
PTK7 | Sgc8 | Daunorubicin-carried aptamer for targeted chemotherapy. | DNA | Lymphoblastic leukemia | [168] |
DOX-carried aptamer for targeted chemotherapy. | DNA | Lymphoblastic leukemia | [169] | ||
DOX-loaded aptamer-tethered DNA nanotrains for targeted chemotherapy. | DNA | Lymphoblastic leukemia | [170] | ||
Aptamers modified MSN to deliver DOX to tumors. | DNA | Lymphoblastic leukemia | [171] | ||
Aptamer-DNAzyme conjugate for targeted gene therapy. | DNA | Cervical carcinoma | [172] | ||
Aptamer modified composite drug nanocarrier based on black phosphorus nanosheets for targeted chemophotothermal therapy. | DNA | Lymphoblastic leukemia | [173] | ||
Nucleolin | AS1411 | DOX-carried aptamer for targeted chemotherapy. | DNA | Hepatocellular carcinoma | [174] |
Melittin conjugated aptamer for targeted chemotherapy. | DNA | Human non-small cell lung cancer | [175] | ||
Dual aptamer modified dendrigraft poly-L-lysin nanoparticles for targeted delivery of DOX. | DNA | Cervical carcinoma | [186] | ||
Aptamer-decorated dextran coated nano-graphene oxide for targeted dextran delivery. | DNA | Breast cancer | [187] | ||
Aptamer-functionalized liposomes loaded with DOX for in vitro and in vivo targeted delivery. | DNA | Breast cancer | [189] | ||
Dual targeting DNA tetrahedron nanocarrier (MUC1-Td-AS1411) for targeted delivery of DOX. | DNA | Breast cancer | [194] | ||
Anti-miR-155-loaded MSNs modified with polymerized dopamine and aptamer for targeted gene therapy. | DNA | Rectal cancer | [200] | ||
Lipophilic aptamer-CpG fused sequences conjugated lipoprotein for targeted delivery of DOX. | DNA | Lung cancer | [202] | ||
Aptamer modified ZnO-gated porMOF-based drug delivery system for targeted delivery for targeted bimodal cancer therapy. | DNA | Cervical carcinoma | [203] | ||
MUC1 | MUC1 | PEGylated aptamer-DOX complex for targeted chemotherapy. | DNA | Breast cancer | [204] |
Aptamer modified and vinorelbine loaded lipid-polymer hybrid nanoparticles for targeted chemotherapy. | DNA | Breast cancer | [206] | ||
Aptamer-conjugated DNA icosahedral nanoparticles as a DOX carrier for targeted chemotherapy. | DNA | Epithelial cell carcinoma | [207] | ||
Quantum dots-aptamer -DOX conjugates for targeted chemotherapy. | RNA | Ovarian cancer | [210] | ||
Epirubicin loaded super paramagnetic iron oxide nanoparticle-aptamer bioconjugate for targeted chemotherapy. | DNA | Colorectal cancer | [211] | ||
Aptamer conjugated chitosan nanoparticles as an anticancer SN38 carrier for targeted chemotherapy. | DNA | Colon cancer | [212] | ||
Aptamer-C1q protein conjugates for targeted immunotherapy. | DNA | Breast cancer | [215] | ||
Mono- and multimeric targeted radiopharmaceuticals based on cyclen ligands coupled with aptamer for targeted radiotherapy. | DNA | Breast cancer | [216] | ||
Aptamer conjugated gold coated superparamagnetic iron oxide nanoparticles for targeted photothermal therapy. | DNA | Colon cancer | [227] | ||
Aptamer coated pDNA/PEI complexes for targeted gene therapy. | DNA | Lung cancer | [218] | ||
MAGE | Ap52 | Phosphonothioate-modified aptamer complexed with DOX for targeted chemotherapy. | DNA | Pancreatic cancer | [219] |
HER2 | HB5 | Aptamer conjugated mesoporous silica nanocarrier-based DOX delivery system for targeted chemotherapy. | DNA | Breast cancer | [221] |
Aptamer functionalized curcumin-loaded human serum albumin nanoparticles for targeted chemotherapy. | DNA | Breast cancer | [220] | ||
CD133 | CD133 | DOX-loaded aptamer for targeted chemotherapy. | DNA | Hepatocellular carcinoma | [222] |
Aptamer-modified docetaxel liposome for targeted chemotherapy. | DNA | Lung cancer | [223] | ||
EpCAM | EpCAM | Aptamer-functionalized mesoporous silica nanoparticles as a DOX carrier for targeted chemotherapy. | DNA | Colon cancer | [224] |
Aptamer and quantum dots-functionalized nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles for targeted chemotherapy. | DNA | Breast cancer | [225] | ||
Aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted chemotherapy. | DNA | Colorectal cancer | [226] |
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Hu, X.; Zhang, D.; Zeng, Z.; Huang, L.; Lin, X.; Hong, S. Aptamer-Based Probes for Cancer Diagnostics and Treatment. Life 2022, 12, 1937. https://doi.org/10.3390/life12111937
Hu X, Zhang D, Zeng Z, Huang L, Lin X, Hong S. Aptamer-Based Probes for Cancer Diagnostics and Treatment. Life. 2022; 12(11):1937. https://doi.org/10.3390/life12111937
Chicago/Turabian StyleHu, Xueqi, Dongdong Zhang, Zheng Zeng, Linjie Huang, Xiahui Lin, and Shanni Hong. 2022. "Aptamer-Based Probes for Cancer Diagnostics and Treatment" Life 12, no. 11: 1937. https://doi.org/10.3390/life12111937