Academic literature on the topic 'IR bioimaging'

A new class of half-sandwich Ir and Ru compounds containing P^P-chelating ligands can be developed as potential multifunctional theranostic platforms that combine bioimaging and anticancer capabilities.

Highly efficient phosphor nanoparticles were prepared with energy transfer from TADF polymer to Ir complex. These nanoparticles exhibited good dispersibility and biocompatibility, which were then used in time-resolved luminescence bioimaging.

Benzannulation of a ditopic ligand affords a significant phosphorescence blue-shift and enhanced emission quantum yield of mono- and dinuclear Ir(iii) complexes. The complexes are excellent oxygen photosensitizers. A use in bioimaging is reported.

Photodynamic therapy (PDT) is a cancer treatment still bearing enormous prospects of improvement. Within the toolbox of PDT, developing photosensitizers (PSs) that can specifically reach tumor cells and promote the generation of high concentration of reactive oxygen species (ROS) is a constant research goal. Mitochondria is known as a highly appealing target for PSs, thus being able to assess the biodistribution of the PSs prior to its light activation would be crucial for therapeutic maximization. Bifunctional Ir(III) complexes of the type [Ir(C^N)2(N^N-R)]+, where N^C is either phenylpyridine (ppy) or benzoquinoline (bzq), N^N is 2,2′-dipyridylamine (dpa) and R either anthracene (1 and 3) or acridine (2 and 4), have been developed as novel trackable PSs agents. Activation of the tracking or therapeutic function could be achieved specifically by irradiating the complex with a different light wavelength (405 nm vs. 470 nm respectively). Only complex 4 ([Ir(bzq)2(dpa-acr)]+) clearly showed dual emissive pattern, acridine based emission between 407–450 nm vs. Ir(III) based emission between 521 and 547 nm. The sensitivity of A549 lung cancer cells to 4 evidenced the importance of involving the metal center within the activation process of the PS, reaching values of photosensitivity over 110 times higher than in dark conditions. Moreover, complex 4 promoted apoptotic cell death and possibly the paraptotic pathway, as well as higher ROS generation under irradiation than in dark conditions. Complexes 2–4 accumulated in the mitochondria but species 2 and 4 also localizes in other subcellular organelles.

Silver nanoparticles are emerging as a powerful tool in bioimaging applications owing to their unique plasmonic properties i.e., extremely high molar extinction coefficients, resonant Rayleigh scattering and enhanced local electromagnetic fields. Through the optimization of these properties, by controlling composition, size, shape, and interparticle spacing of nanoparticles and their assemblies, highly enhanced local electromagnetic fields in the vicinity of nanoparticles are achievable giving rise to IR, Raman and fluorescence surface enhanced spectroscopies (SEIRS, SERS and MEF, respectively).

Fluorescent, ultrabright, stable and cytocompatible flame-made Mn⁵⁺-doped Ba₃(VO₄)₂–Bi₂O₃ nanoparticles are most suitable for near-IR-II bioimaging within 1 cm deep lying tissues outperforming commercial organic fluorophores and quantum dots.

L’imagerie de fluorescence et l'imagerie photo-acoustique (PA) sont deux outils puissants pour la visualisation des tissus et organes biologiques de manière non invasive. Toutefois, ces technologies sont actuellement limitées par le manque d'agents de contraste efficaces. Utiliser des longueurs d’onde de domaine du proche infrarouge (NIR, 650-900 nm), dont l'absorption et la diffusion dans les organismes est relativement faible, permet une imagerie in vivo plus profonde, induit moins d’auto-fluorescence et apporte un bon rapport signal/bruit. Par conséquent, la conception et la synthèse de nouveaux colorants organiques NIR efficaces revêt une importance fondamentale pour l’imagerie de fluorescence ou photo-acoustique. L'encapsulation de colorants organiques dans des nanoparticules dispersibles dans l'eau présente un grand potentiel en imagerie bio-optique, offrant les avantages d'une haute luminosité, d'une bonne photo-stabilité, d'une excellente biocompatibilité et d'une capacité potentielle de ciblage, etc. Notre objectif principal dans cette thèse est de synthétiser de nouvelles molécules organiques pouvant servir d’agents de contraste pour l'imagerie in vivo par fluorescence ou PA
Fluorescence and photoacoustic (PA) imaging are both powerful tools for visualization of biological tissues and organs in non-invasive ways. However, these technologies are limited by the lack of efficient contrast agents. NIR light (650-900 nm) with relatively low absorption and scattering in organisms allows for deeper in vivo imaging, lower auto-fluorescence as well as a good signal to noise ratio. Hence, design and synthesis of efficient NIR organic dyes are of great significance for fluorescence or PA bio-imaging. Meanwhile, encapsulation of organic dyes in nanoparticles dispersible in water present great potential in bio-optical imaging, offering the advantages of high brightness, good photo-stability, excellent biocompatibility and potential targeting ability, etc. Our main goal in this thesis is to synthesize novel organic contrast agents for in vivo fluorescence or PA imaging

This thesis describes the development and synthesis of a range of novel fluorophores based on 1,8-naphthalimide, N-heterocyclic carbene (NHC) and phosphine derivatives, as well as coordination chemistry with Au(I), Ir(III) and Fe(II). Detailed discussions on the characterisation and the photophysical properties are described, with reference to applications including bioimaging, diagnostics and therapeutics. Chapter 2 describes the synthetic development and spectroscopic analysis of a series of NHC-functionalised 1,8-naphthalimide fluorophores, generating ten new ligands that were successfully utilised for Au(I) coordination chemistry. The optical properties of the compounds were dictated by ligand-centred transitions. Cytotoxicity assessments revealed that compounds were the most toxic to LOVO and MCF-7 cell lines. In addition, lysosomal localisation was observed in cell imaging studies with MCF-7 cells, as seen with structurally related anticancer compounds. Chapter 3 describes the synthetic development and spectroscopic analysis of a series of aminophosphine and phosphinite fluorophores, generating six new ligands, with some successfully utilised for Au(I) coordination chemistry. The photophysical properties were explored in detail due to the presence of different fluorescent groups, including naphthalene, anthracene, pyrene and anthraquinone. In this chapter, 31P NMR was particularly important in confirming the success of the synthetic routes. Chapter 4 describes the comparative syntheses of six new phenyl-1H-pyrazoles and their corresponding cyclometalated iridium(III) complexes using both batch and, successfully applied, flow-microwave methodologies. Isolation of spectroscopically pure species in less than 1 hour of reaction time from IrCl3 was observed, along with ligand-dependent, tuneable green-yellow luminescence. Chapter 5 outlines determination of a successful synthetic route to a series of fluorescent electrochemical biosensors that incorporate both a redox active ferrocene unit and a naphthalimide moiety, with the intention to be applied as an electrochemical detection method for Clostridium Difficile (CDF). Detailed photophysical and electrochemical investigations were used to determine suitability for the desired application.

I materiali luminescenti nanostrutturati sono largamente studiati per applicazioni in lampade e display, come scintillatori e nell’imaging biomedico. Pertanto, la ricerca nei nanomateriali prevede lo sviluppo di metodi di sintesi all’avanguardia per il controllo della loro struttura, morfologia e drogaggio. L’utilizzo di polveri nanocristalline per la fabbricazione di nanocompositi permette di ridurre l’incorrere di diverse problematiche come la diffusione della luce emessa; inoltre la dimensione nanometrica dei materiali è un requisito fondamentale per le applicazioni in biotecnologia, per la loro veicolazione attraverso il sangue e la penetrazione nelle cellule. Infine, la realizzazione di nanoparticelle (NP) aventi fase cristallina cubica permetterebbe la progettazione di ceramiche ottiche ad alta densità e quindi di una nuova classe di materiali luminescenti. L’ossido di afnio (HfO2) è stato considerato come fosforo di grande interesse grazie alle sue eccellenti proprietà chimiche e fisiche. In questo lavoro si sono investigate le proprietà di luminescenza e scintillazione di NP di HfO2 di diametro < 5 nm. Le NP pure e drogate con ioni di terre rare (TR) sono state fabbricate attraverso un processo di sintesi appositamente elaborato e ottimizzato. Il lavoro condotto ha permesso di controllare simultaneamente le proprietà strutturali e di luminescenza nelle NP. Particolare attenzione è stata rivolta al ruolo del drogaggio con ioni europio e lutezio tramite sintesi sol-gel non acquosa. L’analisi elementale, la caratterizzazione strutturale e morfologica con XRD, TEM/SEM, insieme alla spettroscopia vibrazionale Raman/IR, hanno confermato la trasformazione della fase cristallina da monoclina a cubica per concentrazioni > 5% mol di ioni Lu3+e Eu3+. Le proprietà ottiche sono state studiate attraverso tecniche di radio- e foto-luminescenza. I risultati ottenuti rappresentano un importante traguardo sia per una migliore comprensione della relazione struttura-proprietà di materiali di dimensione nanometrica, che per l’analisi della applicabilità di questi ultimi in campo tecnologico. In questo lavoro è stata dimostrata la possibilità di modificare lo spettro di emissione delle NP drogando simultaneamente con diverse TR e stabilizzando la fase cubica con l’incorporazione di ioni di Lu3+ otticamente inerte. L’HfO2 è un promettente materiale sia come matrice ospite per le TR che per la sua luminescenza intrinseca. NP non drogate sono state studiate considerando l’effetto della dimensione e della fase cristallina sulla luminescenza. Si è individuata la presenza di una banda di emissione composita nell’intervallo di lunghezze d’onda visibili, possibilmente correlata a difetti di superficie intrinseci o a impurezze del materiale. La sua intensità varia in funzione di trattamenti termici che portano alla modifica della superficie e del diametro delle NP, ed è confrontabile all’efficienza di materiali luminescenti commerciali usati come standard. In parallelo, sono state studiate le proprietà di NP luminescenti per applicazioni biologiche. Le nuove tecniche diagnostiche per immagini in vivo a fluorescenza con alta risoluzione e profondità di penetrazione si basano sulla luminescenza di NP nella finestra di trasparenza del tessuto biologico (1000-1400 nm). Inoltre, l’eccitazione a basse energie porta alla riduzione dell’autofluorescenza generata dai tessuti, componenti intra corporee e molecole organiche della dieta degli animali trattati con le NP. In questa ricerca, è stato dimostrato che l’utilizzo della banda a 1.3 m di ioni di Nd3+ in SrF2 permette di effettuare analisi di biodistribuzione e ottenere immagini in assenza di autofluorescenza e ad alto contrasto. La luminosità, la stabilità chimica e fisica così come l’elevata biocompatibilità rendono le NP di SrF2 promettenti per applicazioni biotecniche, bioimmagini a fluorescenza e future strategie diagnostiche.
Luminescent materials have found a wide variety of applications as phosphors for fluorescent lighting, display devices, X-ray monitoring and imaging, scintillators, and in biomedical imaging. The research on nanostructured materials resulted in the development of novel synthetic methods to control their structure, morphology, and doping. When the size of crystalline powders is tailored down to the nanoscale, several advantages are achieved, like the reduction of the emitted light scattering when fabricating optical nanocomposites. Nanoscale dimensions are also necessary in biotech applications where the material is required to travel in blood vessels and penetrate into cells. Finally, the realization of high density optical ceramics by nanoparticles (NPs) compaction can be pursued, especially with materials that possess cubic crystalline structure, leading to the bottom-up fabrication of a new class of luminescent materials. Hafnium oxide (HfO2) has gained interest in the last years as an attractive nanophosphor because of its excellent physical and chemical properties. In this work, the luminescence and scintillation properties of pure and rare-earth (RE) doped HfO2 NPs with a diameter < 5 nm have been investigated, obtained through a purposely designed synthetic strategy. This work was aimed at controlling the structural properties of NPs while optimizing their optical features. A particular attention has been paid to the role of doping with europium and lutetium ions through the non-aqueous sol-gel method. Structure and morphology characterization by XRD, TEM/SEM, elemental analyses, and Raman/IR vibrational spectroscopies have confirmed the occurrence of the HfO2 cubic polymorph for dopant concentrations larger than 5% mol for trivalent Lu3+ and Eu3+ ions. Optical properties have been investigated by radio- and photo-luminescence spectroscopy. Besides the relevance in application related issues, the results here reported represent an important dataset for a better comprehension of the structure-property relationship in materials confined into nanoscale dimensions. We also demonstrated the possibility of tuning the emission spectrum by multiple RE doping, while deputing the NP cubic structural stabilization to optically inert Lu3+ ions. Given the importance of HfO2 as host material for RE, its intrinsic optical response is also worth of investigation. Undoped HfO2 NPs were studied considering the effect of the size and of the crystal phase. A broad composite emission was observed in the visible range, potentially correlated both to intrinsic surface defects and to impurities. Its intensity can be varied by thermal treatments leading to surface modifications as well as to variations of particle dimensions. Its efficiency has been found to be comparable to that of standard commercial materials, evidencing the potential of pure HfO2 NPs as efficient phosphors. In parallel, we also investigated the use of emitting NPs for biological applications. Novel approaches for high contrast, deep tissue, in vivo fluorescence biomedical imaging are based on infrared-emitting NPs working in the so-called second biological window (1000 -1400 nm), where the partial transparency of tissues allows for the acquisition of high resolution, deep tissue images. In addition, the infrared excitation also leads to a reduction of auto-fluorescence generated by tissues, intra-body components, and specimen's diet. In my work, I exploited how the 1.3m emission band of Nd3+ ions embedded in SrF2 nanoparticles can be used to produce auto-fluorescence free, high contrast fluorescence images and bio-distribution studies. The strong brightness, the chemical and physical stability as well as high biocompatibility make Nd:SrF2 nanocrystals very promising infrared nanoprobes for in vivo imaging experiments in the second biological window.

The remarkable versatility and the outstanding photophysical properties of heavy transition metal complexes prompted towards the design of innovative cyclometalated Pt(II) and Ir(III) complexes with enhanced luminescence. Indeed, the long life-time of the excited states and the possibility to finely tune the phosphorescence phenomenon through minor modifications of the organic backbone makes them attractive for bioimaging, photodynamic therapy and OLEDs application. In this context, the introduction of sterically hindered substituents and of biologically relevant substrates such as glucose and tryptophan on the organic framework was successfully achieved, thus obtaining excellent emitters characterized by increased brightness and selectivity towards tumorous cells. The present thesis provides an extensive discussion concerning the theoretical basis underlying the design of the developed luminophores, the synthetic pathways followed, and the remarkable results obtained. Notably, the designed Pt(II) complexes exhibited extraordinary photophysical properties that have never reported in literature before.

This dissertation contains the synthesis and characterization of squaraine based new functional materials. In the first part of this thesis work, a water soluble benzothiazolium squaraine dye was synthesized with pyridium pendents, and controlled aggregation properties were achieved. After formation of partially reversible J-aggregation on a polyelectrolyte (poly(acryl acid) sodium salt) template, the nonlinear, two-photon absorption cross section per repeat unit was found to be above 30-fold enhanced compared with nonaggregate and/or low aggregates. Using a similar strategy, sulfonate anions were introduced into the squaraine structure, and the resulting compounds exhibited good water solubilities. A 'turn on' fluorescence was discovered when these squaraine dyes interacted with bovine serum albumin (BSA), titration studies by BSA site selective reagents show these squaraine dyes can bind to both site I and II of BSA, with a preference of site II. Introduction of these squaraine dyes to BSA nanoparticles generated near-IR protein nano fabricates, and cell images were collected. Metal sensing properties were also studied using the sulfonates containing a benzoindolium squaraine dye, and the linear response of the absorption of the squaraine dye to the concentration of Hg2+ makes it a good heavy metal-selective sensing material that can be carried out in aqueous solution. Later, a squaraine scaffold was attached to deoxyribonucleosides by Sonogashira coupling reactions, in which the reaction conditions were modified. Iodo-deoxyuridine and bromo-deoxyadenosine were used as the deoxyribonucleosides building blocks, and the resulting squaraine dye-modified deoxyribonucleosides exhibited near-IR absorption and emission properties due to the squaraine chromophore. Interestingly, these non-natural deoxyribonucleosdies showed viscosity dependent photophysical properties, which make them nice candidates for fluorescence viscosity sensors at the cellular level. After incubation with cells, these viscosity sensors were readily uptaken by cell, and images were obtained showing regions of high viscosity in cells.
Ph.D.
Doctorate
Chemistry
Sciences
Chemistry

碩士
國立中山大學
化學系研究所
103
Semiconducting polymer dots (Pdots) have recently emerged as a new class of extraordinarily bright fluorescent probes with promising applications in biological imaging and sensing. Herein we synthesized a novel series of highly emissive orange-fluorescent copolymers, poly[9,9-dioctylfluorenyl-2,7-diyl)-co-1,4-benzo-{2,19-3}-selenadiazole)] (PFBS) and tuned the ratio of fluorene to benzoselenadiazole (BS) from 98 : 2 to 50 : 50 to investigate the influence of BS molar ratio on the emission properties of the resulting Pdots. An optimal quantum yield of 44% could be obtained for PFBS Pdots at a fluorene to BS ratio of 70 : 30. These PFBS Pdots also exhibited great photostability and superior single-particle brightness. We next conjugated biomolecules onto the surface of these PFBS Pdots and demonstrated their ability for specific cellular labeling without any noticeable nonspecific binding. We are now working on the synthesis of near-infrared Pdots based on this BS unit and anticipate this series of ultrabright Pdots will be very useful in a variety of in vitro and in vivo bioimaging applications. In recent years, semiconducting polymer dots (Pdots) have emerged as a new class of extraordinarily bright fluorescent probes with burgeoning applications in biological imaging and sensing. With the increasing demand for near-infrared (NIR)-emitting probes for in vivo biological measurements, the direct synthesis of semiconducting polymers that can form Pdots with ultrahigh fluorescence brightness are extremely lacking due to the severe aggregation-caused quenching of the NIR chromophores in Pdots. Here we describe the design and synthesis of dithienylbenzoselenadiazole (DBS)-based NIR-fluorescing Pdots with ultrahigh brightness and excellent photostability. More importantly, the fluorescence quantum yields of these Pdots could be effectively increased by the introduction of long alkyl chains into the thiophene rings of DBS to significantly inhibit the aggregation-caused emission quenching. Additionally, these new series of DBS-based Pdots can be excited by a commonly used 488 nm laser and show a fluorescence quantum yield as high as 36% with a Stokes shift larger than 200 nm. Single-particle analysis indicates that the per-particle brightness of the Pdots is at least 2 times higher than that of the commercial quantum dot (Qdot705) identical laser excitation and acquisition conditions. We also functionalized the Pdots with carboxylic acid groups and then conjugated biomolecules onto the surface of Pdots to demonstrate their capability for specific cellular labeling without any noticeable nonspecific binding. Our results suggest that these DBS-based NIR-fluorescing Pdots will be very useful in a variety of bioimaging and analytical applications.

The recent advances in nanoscience and technology have opened new avenues for carbon-based nanomaterials. Especially, Carbon dots (CDs) have gained significant attention due to their simple, economic and rapid green synthesis. These materials exhibit excellent water solubility, fluorescence emission, high fluorescence quantum yield, Ultraviolet (UV) to Infrared (IR) range absorbance and high bio-compatibility. Therefore, these materials are widely used for various biological applications including bio-imaging. With the integration and doping of surface passive agents and elements, respectively influenced the enhancement of fluorescence property of CDs. Also, the conjugation of receptor-based targeting ligands leads to targeted bioimaging. CDs in combination with other imaging contrast agents lead to the development of novel contrast agents for bimodal imaging and multimodal imaging techniques. The combination of diagnostic CDs with therapeutic agents resulted in the formation of theragnostic CDs for image guided therapies. In this chapter, a comprehensive view on the top-down and bottom–up green synthesis methods for naturally derived CDs discussed. Further, unique physical, chemical, optical and biological properties of CDs described. Finally, fluorescence based bimodal and multimodal imaging techniques also described.

Semiconductor nanocrystals have unique optical properties due to quantum confinement effects, and a variety of promising approaches have been devised to interface the nanomaterials with biomolecules for bioimaging and therapeutic applications. Such bio-interface can be facilitated via a DNA template for nanoparticles as oligonucleotides can mediate the aqueous-phase nucleation and capping of semiconductor nanocrystals.[1,2] Here, we report a novel scheme of synthesizing fluorescent nanocrystal quantum dots (NQDs) using DNA aptamers and the use of this biotic/abiotic nanoparticle system for growth inhibition of MCF-7 human breast cancer cells for the first time. Particularly, we used two DNA sequences for this purpose, which have been developed as anti-cancer agents: 5-GGT GGT GGT GGT TGT GGT GGT GGT GG-3 (also called, AGRO) and 5-(GT)15-3.[3–5] This study may ultimately form the basis of unique nanoparticle-based therapeutics with the additional ability to optically report molecular recognition. Figure 1a shows the photoluminescence (PL) spectra of GT- and AGRO-passivated PbS QD that fluoresce in the near IR, centered at approximately 980 nm. A typical synthesis procedure involves rapid addition of sodium sulfide in the mixture solution of DNA and Pb acetate at a molar ratio of 2:4:1. The resulting nanocrystals are washed to remove unreacted DNA and ions by adding mixture solution of NaCl and isopropanol, followed by centrifugation. The precipitated nanocrystals are collected and re-suspended in aqueous solution by mild sonication. Optical absorption measurements reveal that approximately 90 and 77% of GT and AGRO DNA is removed after the washing process. The particle size distribution in Figure 1b suggests that the GT sequence-capped PbS particles are primarily in 3–5 nm diameter range. These nanocrystals can be easily incorporated with mammalian cells and remain highly fluorescent in sub-cellular environments. Figure 1c serially presents an optical image of a MCF-7 cell and a PL image of the AGRO-capped QD incorporated with the cell. Figure 1. (a) Normalized fluorescence spectra of PbS QD synthesized with GT and AGRO sequences, which were previously developed as anti-cancer agents. The DNA-capped QD fluoresce in the near IR centered at ∼980 nm. (b) TEM image of GT-templated nanocrystals ranging 3–5 nm in diameter. (c) Optical image of an MCF-7 human breast cancer cell after a 12-hour exposure to aptamer-capped QD. (d) PL image of AGRO-QD incorporated with the cell, indicating that these nanocrystals remain highly fluorescent in sub-cellular environments. One immediate concern for interfacing inorganic nanocrystals with cells and tissue for labeling or therapeutics is their cytotoxicity. The nanoparticle cytotoxicity is primarily determined by material composition and surface chemistry, and QD are potentially toxic by generating reactive oxygen species or by leaching heavy metal ions when decomposed.[6] We examined the toxicity of aptamer-passivated nanocrystals with NIH-3T3 mouse fibroblast cells. The cells were exposed to PbS nanocrystals for 2 days before a standard MTT assay as shown in Figure 2, where there is no apparent cytotoxicity at these doses. In contrast, Pb acetate exerts statistically significant toxicity. This observation suggests a stable surface passivation by the DNA aptamers and the absence of appreciable Pb2+ leaching. Figure 2. Viability of 3T3 mouse fibroblast cells after a 2-day exposure to DNA aptamer-capped nanocrystals. There is no apparent dose-dependent toxicity, whereas a statistically significant reduction in cell viability is observed with Pb ions. Note that Pb acetate at 133 μM is equivalent to the Pb2+ amount that was used for PbS nanocrystal synthesis at maximum concentration. Error bars are standard deviations of independent experiments. *Statistically different from control (p&lt;0.005). Finally, we examined if these cyto-compatible nanoparticle-aptamers remained therapeutically active for cancer cell growth inhibition. The MTT assay results in Figure 3a show significantly decreased growth of breast cancer cells incorporated with AGRO, GT, and the corresponding templated nanocrystals, as anticipated. In contrast, 5-(GC)15-3 and the QDs synthesized with the same sequence, which were used as negative controls along with zero-dose control cells, did not alter cell viability significantly. Here, we define the growth inhibition efficacy as (100 − cell viability) per DNA of a sample, because the DNA concentration is significantly decreased during the particle washing. The nanoparticle-aptamers demonstrate 3–4 times greater therapeutic activities compared to the corresponding aptamer drugs (Figure 3b). We speculate that when a nanoparticle-aptamer is internalized by the cancer cells, it forms an intracellular complex with nucleolin and nuclear factor-κB (NF-κB) essential modulator, thereby inhibiting NF-κB activation that would cause transcription of proliferation and anti-apoptotic genes.[7] The nanoparticle-aptamers may more effectively block the pathways for creating anti-apoptotic genes or facilitate the cellular delivery of aptamers via nanoparticle uptake. Our additional investigation indicates that the same DNA capping chemistry can be utilized to produce aptamer-mediated Fe3O4 nanocrystals, which may be potentially useful in MRI and therapeutics, considering their magnetic properties and biocompatibility. In summary, the nanoparticle-based therapeutic schemes developed here should be valuable in developing a multifunctional drug delivery and imaging agent for biological systems. Figure 3. Anti-proliferation of MCF-7 human breast cancer cells with aptamer-passivated nanocrystals. (a) Viability of MCF-7 cells exposed to AGRO and GT sequences, and AGRO-/GT-capped QD for 7 days. The DNA concentration was 10 uM, while the particles were incubated with cells at 75 nM. (b) Growth inhibition efficacy is defined as (100 − cell viability) per DNA to correct the DNA concentration after particle washing.