Advantages and Applications of Aptamer Conjugated Nanoparticles

What is the aptamer conjugated nanoparticle?

Aptamer-conjugated nanoparticles exemplify a sophisticated category of nanomedicine that integrates the exceptional specificity of aptamers—short, single-stranded DNA or RNA molecules that can adopt unique three-dimensional configurations—with the multifunctional capabilities of nanoparticles to optimize targeted drug delivery, diagnostic functions, and therapeutic interventions. This novel strategy leverages the distinctive molecular recognition attributes of aptamers alongside the beneficial characteristics of nanoparticles, resulting in highly precise biomedical instruments that offer potential advancements in precision medicine.

Aptamers are synthetic oligonucleotides that could bind with remarkable selectivity and affinity to many targets, including proteins, tiny molecules, and whole cells, owing to their capacity to assume intricate three-dimensional structures. These molecular binding agents operate analogous to antibodies but have several benefits, including simpler chemical manufacturing, reduced immunogenicity (thereby minimizing the likelihood of eliciting immune responses), and enhanced stability across diverse biological settings. Nanoparticles, manufactured at the nanoscale and consisting of various materials such as gold, silver, silica, polymers, or lipids, function as vehicles or carriers for the delivery of medications, imaging agents, or other therapeutic compounds. Owing to their nanoscale dimensions, these particles demonstrate augmented interactions with biological systems, including greater tissue penetration, and may be precisely guided to deliver their payloads to specific sites inside the body. Conjugation entails the binding of aptamers to nanoparticle surfaces, usually by covalent bonds or other robust interactions. This combination enables the aptamer-conjugated nanoparticles to serve as targeted delivery systems, facilitating their binding to specific sick cells or tissues with great accuracy. This focused method enables the direct administration of therapeutic drugs to disease locations, such as tumors, while reducing possible adverse effects on healthy tissues, thereby enhancing therapeutic efficacy.

Aptamer conjugation with gold nanoparticles (AuNP). (Schmitz F R W., et al., 2020)

Various types of aptamer conjugates. (Kumar S., et al., 2024)

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Applications of aptamer-conjugated nanoparticles

Detection of cancer cells: In order to identify tumor markers, Aptamer-conjugated gold nanoparticles (Apt-AuNPs) have been used in diagnostic investigations. The DNA-aptamer was engineered and attached to surfaces of AuNPs, which were supported with α-cyclodexterin and had varying morphologies, in order to achieve high selectivity for platelet-derived growth factor (PDGF). Depending on the size and shape of the AuNP, these aptasensors showed varying electrochemical activity toward PDGF redox. In an ideal setting, the aptasensors were used to detect PDGF using square wave voltammetry (SWV) and cyclic voltammetry (CV) methods; they showed a linear range of 0.52-1.52 nM and a limit of detection of 0.52 nM. The cubic aptasensor also performed well when it came to determining the concentration of MCF-7 cells; it had a linear range of 328-593 cells/ml and a limit of quantification of 328 cells/ml. A hairpin oligonucleotide aptamer was created with biotin attached to the 3' end and an immobilized S-bond on the surface of the AuNPs. It has a 25-base loop that is complementary to MUC1. Additionally, the surface of the particles included horseradish peroxidase (HRP). A dual-labeled aptasensor particle was produced by combining all of these. Also created was an electrode that used glassy carbon with streptavidin adsorbed on it and multiwalled carbon nanotubes (MWCNTs). When MUC1 is present, the aptamer unfolds, allowing the streptavidin to reach the biotin and produce signals. By using the electrochemical reduction signal of DAP, MUC1 may be detected by immersing the modified electrodes in solutions of H2O2 and o-phenylenediamine (OPD). The linear range and limit of detection for this technique were 8.8–353.3 nM and 2.2 nM, respectively.

Pathogen detection: Pathogen identification is one potential use of Apt-AuNPs. In order to detect Salmonella typhimurium in pork meat samples, one research created a portable device that does not require labels. An LSRP sensing device with a 1.0 × 104 cfu/ml limit of detection was created by conjugating aptamers on a 20 nm AuNP monolayer. Using a linear range of 0.2-50 nmol/L and a limit of detection of 0.07 nmol/L, an aptasensor for prion protein detection was created in another study. The aptasensor relies on resonant light scattering (RLS), which is improved with the help of AuNPs when prion protein is present.

Protein detection: Using unmodified Apt-AuNPs, one research devised a colorimetric-based method for thrombin detection. The aptamer they utilized was capable of folding into a G-quadruplex/duplex, a type of duplex structure. As a result of its unfolded structure, this aptamer is able to attach to the surface of AuNPs, protecting them against aggregation and the red-to-blue color change caused by high salt concentration. When this aptamer is present in a solution, its folded and unfolded forms are in balance with one another. The addition of thrombin induces aptamer folding into the stated structure, rendering the AuNPs vulnerable to salt. Salt makes the AuNPs aggregate, and the resulting color shift is obvious to the human sight. This method was found to have a limit of detection of 0.83 nM and a linear range of 0-167 nM.

Targeted drug delivery: A research initiative established a nano-sized liposomal co-delivery system termed Aptm[DOX/IDO1], which incorporates an immunogenic cell death (ICD) inducer (doxorubicin, DOX) and IDO1 siRNA, utilizing cationic liposomes conjugated with two distinct DNA aptamers, specifically anti-CD44 and anti-PD-L1, to target cancer cell surface markers and facilitate immunotherapy and tumor microenvironment (TME) modulation. DOX was utilized as the ICD inducer to eliminate cancer cells and stimulate an anticancer immune response through the recruitment of CTLs in the TME, while IDO1 siRNA was included to attain a synergistic effect by suppressing the DOX-induced IDO1 upregulation. The Aptm[DOX/IDO1] selectively targeted CD44- and PD-L1-expressing breast cancer cells, facilitating efficient delivery of DOX and IDOI siRNA via aptamer-mediated endocytosis. The endocytosed Aptm[DOX/IDO1] successfully elicited immunogenic cell death and inhibited IDO1 expression in target breast cancer cells, demonstrating significant cytotoxicity. Aptm[DOX/IDO1] injection into tumor-bearing mice effectively inhibited tumor development by enhancing CD8+ CTL infiltration and altering the immunosuppressive tumor microenvironment in vivo.

Aptamer conjugated nanoparticle for immunogenic chemotherapy. (Kim M., et al., 2022)

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Advantages of aptamer conjugated nanoparticle

High specificity and affinity: Aptamers exhibit remarkable specificity for their target molecules, including proteins, tiny compounds, or cells. When coupled to nanoparticles, this selectivity enables the nanoparticle to precisely target sick cells or tissues, therefore minimizing off-target effects. This selectivity parallels that of antibodies; however, aptamers provide the additional advantages of enhanced synthesis and modification ease.

Reduced immunogenicity: Aptamers are synthesized nucleic acids, rendering them far less likely to elicit an immune response compared to protein-based agents such as antibodies. The minimal immunogenicity is especially beneficial for repeated delivery in patients, rendering the aptamer-conjugated nanoparticles safer for prolonged therapy.

Enhanced Targeting: A principal advantage of aptamer-conjugated nanoparticles is their capacity to improve the targeted distribution of medications or therapeutic agents to particular locations inside the body. Nanoparticles can be infused with pharmaceuticals or other therapeutic agents and directed to their targets via aptamers that recognize specific disease indicators, such as proteins that are overexpressed on cancer cells. This guarantees an increased concentration of the medicine at the target location, enhancing therapeutic efficacy and minimizing systemic toxicity. This focused methodology is especially beneficial in oncological medicines, because traditional treatments may harm good cells.

Stability and biocompatibility: Aptamers possess more stability than antibodies under many environmental circumstances, including fluctuations in temperature and pH. Aptamer-conjugated nanoparticles exhibit enhanced resilience when introduced into the intricate physiological environment of the human body. Moreover, some nanoparticle formulations, including those derived from lipids or biodegradable polymers, exhibit biocompatibility, indicating their capacity for safe degradation and elimination by the body, hence minimizing the potential for undesirable immune reactions or toxicity.

Versatility in functionalization: Aptamer-conjugated nanoparticles can be readily altered or functionalized for many uses. Nanoparticles may be customized with diverse surface characteristics, dimensions, and compositions, whereas aptamers can be chosen to interact with a broad spectrum of targets, ranging from tiny molecules to whole cells. This adaptability renders these systems suitable for various biological applications, including targeted drug administration, diagnostics, imaging, and therapeutic purposes. Nanoparticles may transport many payloads, including pharmaceuticals, imaging agents, or genetic materials such as RNA or DNA, rendering them multipurpose instruments for precision medicine.

Limitations of aptamer conjugated nanoparticle

Short circulation time: Aptamer-conjugated nanoparticles frequently encounter obstacles associated with fast elimination by the reticuloendothelial system (RES), predominantly via the liver and spleen. This may lead to a brief circulation duration, diminishing the quantity of nanoparticle-drug complexes that get to the target tissues. Surface changes such as PEGylation can be beneficial; nonetheless, improving biodistribution continues to pose a significant difficulty.

Degradation by nucleases: Despite aptamers being typically more stable than antibodies, they are susceptible to destruction by nucleases in the circulation. This constrains their efficacy in vivo, as aptamers may deteriorate before to reaching their target. Chemical changes, like the incorporation of artificial bases or polyethylene glycol (PEG) conjugation, might enhance stability but may complicate manufacturing and elevate prices.

Challenges in large-scale production: While aptamers may be chemically produced, large-scale production with uniform quality can be intricate. The conjugation of aptamers to nanoparticles is labor-intensive, necessitating meticulous control to guarantee consistency and repeatability. This complicates large-scale manufacture for therapeutic applications, particularly in comparison to more established drug-delivery techniques.