Synthesis
Several routes have been used to synthesize QDs
22
but, generally, techniques for QD synthesis used top-down processing methods and bottom-up approach. Top-down processing methods include molecular beam epitaxy (MBE), ion implantation, e-beam lithography, and X-ray lithography. Using the alternative bottom-up approach, colloidal QDs are prepared by self-assemblyin the solution following a chemical reduction
23
24
25
26
.
In the approaches of top-down, for making the QDs, a bulk semiconductor is thinned. For the achieve QDs of diameter approximately 30 nm, electron beam lithography, reactive-ion etching, and/or wet chemical etching are commonly used. For systematic experiments on quantum confinement effect, controlled shapes and sizes are achievable with the desired packing geometries. Alternatively, focused ion or laser beams have also been used to fabricate arrays of zero-dimension dots. Incorporation of impurities into the QDs and structural imperfections by patterning are major disadvantages with these processes
22
.
A number of different self-assembly techniques (bottom-up) have been used to synthesize the QDs, and they may be broadly subdivided into wet-chemical and vapor-phase methods
22
: (a) wet-chemical methods mainly follow the conventional precipitation methods with careful control of parameters for a single solution or mixture of solutions. The precipitation process invariably involves both nucleation and limited growth of nanoparticles. Nucleation may be categorized as homogeneous, heterogeneous, or secondary nucleation
27
. Homogeneous nucleation occurs when solute atoms or molecules combine and reach a critical size without the assistance of a pre-existing solid interface. Wet-chemical methods are generally microemulsion, sol–gel
28
29
30
, competitive reaction chemistry, hot-solution decomposition
31
32
33
, sonic waves or microwaves
34
, and electrochemistry. (b) Vapor-phase methods for producing QDs begin with processes in which layers are grown in an atom-by-atom process. Consequently, self-assembly of QDs occurs on a substrate without any patterning
35
36
37
38
. Self-assembly of nanostructures in material grown by MBE, sputtering, liquid metal ion sources, or aggregation of gaseous monomers are generally categorized under vapor-phase methods
22
. MBE has been mainly used to self-assemble QDs from III-V semiconductors and II-VI semiconductors using the large lattice mismatch, e.g., InAs on GaAs has a 7% mismatch and leads to SK growth
35
.
Applications
In this review, we evaluate few experiments that show the high potential of QDs in biological application, including tracking different macromolecules in the cell, tracking various cells in the tissue, labeling organelles and cells, clinical applications, and other applications
39
40
41
42
43
.
QDs for labeling cells
Because QDs have constant and unique optical properties, they are the best candidate for cell labeling, as compared with organic dyes.
Use in plant bioimaging There is an increasing application of QD as markers for the cells or cell walls (CWs) in plant science. A first target location for external agents in a plant cell is the CW
44
. Djikanović et al. demonstrated that CdSe QDs bind typically to cellulose and lignin in the cell wall of Picea omorika branch. Respectively, binding to lignin and cellulose are achieved by interaction with the chains of C = C and C-C alternating bonds and interaction with the OH groups
44
. Data showed that QDs are suitable for homogenous marking of the whole cell wall. This is a consequence of the structural arrangement of the cell wall polymers in the whole cell wall network as well as the extremely small size of the QDs. These characteristics enable a feasible penetration of the nanoparticles inside the polymer structures in the CW composite
44
.
Use in animal bioimaging Goldman et al. used biotinylated CTxB in conjunction with QD-avidin conjugates
45
for labeling of the live HeLa cells which Figure 1 shows an image of the lateral membrane staining for GM1 ganglioside using QDs (in red) and nuclear staining using Hoechst (in blue). Punctuate labeling of the cell surface by QD bioconjugate is typical for molecules such as GM1 that is present in membrane rafts
46
.
<p>Figure 1</p>Live HeLa cells growing on a glass coverslip
Live HeLa cells growing on a glass coverslip. Labeled with QD-avidin for GM1 (in red) and Hoechst 3342 for nuclear staining (in blue) 46.
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In another study, they labeled live HeLa cells which were biotinylated using sulfo-NHS-SS biotinylating reagent and then incubated with the avidin-conjugated yellow-emitting QDs. It is shown in Figure 2
47
.
<p>Figure 2</p>HeLa cells labeled with the avidin-conjugated yellow-emitting QDs
HeLa cells labeled with the avidin-conjugated yellow-emitting QDs.47. (A) Image of cells immediately after the unbound QDs were removed in which labeling is restricted to the cell surface. (B) Image of a cell that was allowed to grow for 2 h after washing out of unbound QDs.
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For long-term live cell imaging, Hasegawa et al. used the CHPNH2-QD complexes which were uniformly internalized into the cells without being aggregated. Therefore, CHPNH2 nanogel has high potential for use in long-term live cell imaging. The interaction of QDs with cells was successfully controlled by the amino group content of the CHPNH2 nanogel
48
.
Use in prokaryote bioimaging Sensitive and selective staining of bacterial mutants using QD labels was demonstrated by Smith's group. This principle of detection is based on selective targeting affinity of Zn(II)-dipicolylamine coordination complex to phospholipids on the bacterial cell surface of specific strain as shown in Figure 3
49
50
.
<p>Figure 3</p>Imaging of rough Escherichia coli JM83 cells
Imaging of rough Escherichia coli JM83 cells. Left imaging is red QD, and right imaging is green QD. Scale bar is 2 μM 49.
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In another study, authors demonstrated the use of magnetic beads coated with anti-E.coli O157 antibodies and streptavidin-coated QDs for measuring the bacterial cell concentration
51
. Yang and Li, using QDs with different emission wavelengths (525 nm and 705 nm), reported the simultaneous detection of E. coli O157:H7 and Salmonella typhimurium
52
.
Tracking different particles
With the application of new imaging methods and the use of brighter and more stable probes, such as QDs, single particle tracking has the potential to enter into a new era of high resolution and long timescale imaging
53
54
55
. SPT techniques allow scientists to follow single molecules in real time and visualize the actual molecular dynamics in their habitant environment.
For extracellular study Because QDs do not require intracellular delivery through the impermeable plasma membrane, membrane receptors or membrane-associated proteins are intuitive targets for QD imaging
53
. Howarth et al. demonstrated a method to track endogenous cell-surface proteins without cross-linking by purifying monovalent antibody-QD conjugates. They approach to make monovalent tight-binding QDs, using mSA, which could be applied to other nanoparticles that show sufficient electrophoretic mobility. They applied sQD-mSA1 to study the mobility of a mutant of low-density lipoprotein (LDL) receptor with a truncated cytosolic tail, originally found from an individual with familial hypercholesterolemia. This mutant phenotype has been extensively investigated by following LDL, but Howarth and co-workers analyzed the behavior of the receptor itself (supplementary methods). They imaged single monovalent sQDs bound to the biotinylated AP-LDL receptor, as indicated by QD fluorescence intensity and blinking. The mobility of mutant receptors labeled with sQD-mSA1 was significantly greater than that of labeled wild-type LDL receptor (P = 1.6 × 10−14)
56
.
In similar studies, recently, QDs used to target membrane proteins and investigate the mobility and entry-exit kinetics in several systems: (1) various transmembrane proteins, for example, integrins
57
, channels
58
, and aquaporines
59
; (2) receptors GABA
60
, glycine
61
, interferon
62
, and HER
63
64
; and (3) neurological synapse
65
66
.
For intracellular study In one of the study, the advantages of the broad, continuous excitation spectrum were demonstrated in a dual-emission, single-excitation labeling experiment on mouse fibroblasts. These nanocrystal probes are, thus, complementary and, in some cases, may be superior to existing fluorophores
4
. Nonspecific labeling of the nucleus by both the red and the green probes resulted in a yellow color. The red actin filaments were specifically stained. Also, the green probes penetrate into the nucleus. Both are shown in Figure 4
4
.
<p>Figure 4</p>
Image was obtained with 363-nm excitation and × 40 oil 1.3 numerical aperture objective
Image was obtained with 363-nm excitation and × 40 oil 1.3 numerical aperture objective.
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This is shown as green color for nucleus and red color for actin filaments. Nonspecific labeling of the nucleus by both the red and the green probes resulted in a yellow color
4
.
Superior stability of QD fluorophores gives the possibility to improve quantitation of FISH analysis of human chromosomal changes. Xiao and Barker have investigated coated (CdSe)ZnS QDs as fluorescence labels for FISH of biotinylated DNA to human lymphocyte metaphase chromosomes under conditions that approximate those commonly found in clinical cytogenetics laboratories
67
. They have also demonstrated the application of QDs to FISH detection of the clinically relevant HER2 locus in breast cancer cells (Figure 5).
<p>Figure 5</p>Qualitative FISH detection of HER2 gene-amplified SK-BR-3 breast cancer cells
Qualitative FISH detection of HER2 gene-amplified SK-BR-3 breast cancer cells. With (A) streptavidin-conjugated Qdot605 and (B) FITC, respectively 67.
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Pierobon et al.
68
and Nelson et al.
69
tagged myosin V molecules with QDS toestablish a link between in vitro and in-cell measurements of myosin V motors. Then, the complex myosin V/QD (MyoV::QD), using the pinocytic influx, was introduced into the cells.
Yoo et al.
70
and Courty et al.
71
characterized the dynamics of other major actors of intracellular transport: the kinesin-1, the actin filaments, and the microtubules
65
.
Imaging in situ
Imaging of the satellite cells in rat intact and injured soleus muscles using quantum dots The employment of satellite cells, which are located between the basement membrane and the plasma membrane in myofibers, is required for myofiber repair after muscle injury or disease. Using QDs conjugated to anti-M-cadherin antibody, Ishido and Kasuga attempted the visualization of satellite cells in both intact and injured skeletal muscle of rat in situ. They demonstrated in situ real-time imaging of satellite cells localized within the skeletal muscle (Figure 6)
72
.
<p>Figure 6</p>Double fluorescence staining to visualize the localization of M-cadherin (in red) and nuclei (in blue)
Double fluorescence staining to visualize the localization of M-cadherin (in red) and nuclei (in blue). Arrows indicate that M-cadherin-positive satellite cells were located within the intact soleus muscle in situ72.
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Imaging morphogenesis in Xenopus with quantum dot nanocrystals Stylianou and Skourides are the first to report the use of near-infrared QDs to image mesoderm migration in vivo with single cell resolution and provide quantitative in vivo data regarding migration rates
73
.
Navarro et al. experiments revealed that Arabidopsis exposed to QDs that are dispersed in Hoagland's solution for 1 to 7 days did not internalize intact QDs. Fluorescence microscopy showed strong evidence that the QDs were generally on the outside surfaces of the roots (Figure 7). The amount of QDs adsorbed is dependent on the stability of the QDs in suspension
74
.
<p>Figure 7</p>Imaging of roots from plants exposed to QD suspension in HS + HA
Imaging of roots from plants exposed to QD suspension in HS + HA. For (A) 1 and (B) 7 days 74.HS, Hoagland's solution; HA, one of the important groups of organic acids.
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Using QDs in clinical applications
The development of multifunctional nanomaterials combining diagnostic and therapeutic purpose has recently attracted intensive interests
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76
77
78
79
80
81
. In this paper, we have reviewed the clinical applications of QDs in the three categories that include: (1) biomarker detection in various cancers, (2) imaging and sensing of infectious diseases, and (3) other clinical therapeutic applications.
Biomarker detection in various cancers using QDs The detection of cancer biomarkers is important for diagnosis, disease stage forecasting, and clinical management
82
. QDs with intense and stable fluorescent properties could enable the detection of tens to hundreds of cancer biomarkers in blood assays, on cancer tissue biopsies, or as contrast agents for medical imaging. Clinical outcome of cancer diagnosis is highly dependent on the stage at which the malignancy is detected, and therefore, early screening has become extremely important in any type of cancer
83
.
1. Multicolor and multiplexing potentialities of QDs are used for the detection of four protein biomarkers CD15, CD30, CD45, and Pax5 of Hodgkin's lymphoma from lymphoma tissues. Simultaneous visualization using multiplexed QD staining was advantageous for the selective identification of rare Hodgkin (Reed-Sternberg) cells, a primary diagnostic target for Hodgkin's disease, which was not achievable using traditional immunohistochemistry assays
84
85
.
2. Yu et al. reported the use of GSH-TGA-QDs-ND-1 probes to label colorectal cancer cells CCL187. They prepared QDs, which were conjugated with monoclonal antibody ND-1 for specific reaction with antigen LEA
86
.
3. In the United States, pancreatic cancer is the fourth leading cause of cancer death (about 18,770 men and 18,030 women (36,800 people) in 2010)
87
. Using semiconductor QD-antibody conjugates, Lee et al. demonstrated quantitative profiling of biomarkers for pancreatic cancer at the single-cell level. Their results show the possibility of this method for staging and forecasting, such as prostate stem cell antigen claudin-4, and mesothelin, which are expressed in different stages of progression of pancreatic cancer
82
. Anyway, realizing quantitative profiling requires stable quantum yield, monodisperse QD-Ab conjugates, and well-defined surface chemistry
88
.
There are evidences showing the application of QDs in micro- and nanoarrays for the detection of cancer biomarkers
83
.
Imaging and sensing of infectious diseases by QDs QDs have become one of the most hopeful and interesting materials for diagnostic applications of bioimaging, labeling, and sensing for infectious diseases such as respiratory syncytial virus (RSV)that isone of the families of Paramyxoviridae
50
. In Table 1, some of the infectious diseases and QDs used to distinguish them are shown.
<p>Table 1</p>
Some of the infectious diseases and QDs used to distinguish them
Authors
Type of infectious diseases
In vitro / in vivo
Type of modified QDs
Other clinical therapeutic applications.
Tripp et al.
89
RSV
In vitro/in vivo
Antibody anti-F protein conjugated to QDs(CdTe)
Agrawal et al.
90
Individual molecules of genes, proteins, and virus particles
In vivo
QD-antibody color-coded NP probes and two-color co-localization imaging
Bentzen et al.
91
RSV
In vivo
Streptavidin-coated QDs conjugated to antibody anti-F and antibody anti-G
Dwarakanath et al.
92
S. typhimurium
In vivo
Antibody-QD and DNA aptamer-QD
E. coli
B. subtilis spores
Goldman et al.
93
Choleratoxin, ricin, shinga-like toxin1 and staphylococcal enterotoxin B
In vitro
Antibody-QD (CdSe/Zns)
Zhao et al.
94
Food-borne pathogenic E. coli O157:H7, S. typhimurium and S. flexneri
QDanti-S. flexneri antibody,anti-E. coli antibody, anti-S. typhimurium antibody
Hahn et al.
95
Single cells of E.coli O157:H7
Streptavidin-coated QDs conjugated to antibody
Mukhopadhyay et al.
96
Detect E. coli at levels as low as 104 bacteria/ml of sample
Mannose-conjugated QDs
Edgar et al.
97
Mycobacterium
In vivo
Streptavidin-coated QDs conjugated to phage
B. anthracis
Zhu et al.
98
C. parvum
QD-conjugated antibodies
G. lamblia
Klostranec et al.
99
Biomarkers of the most globally prevalent blood-borne infectious diseases (i.e., hepatitis B, hepatitis C, and HIV) with low sample volume
QD-antibody
Gazouli et al.
100
Mycobacterium genus
In vivo
Specific DNA sequences combining QDs with magnetic beads
101
102
Hahn et al.
95
Individual pathogenic E. coli O157:H7 in phosphate buffer saline solution
Streptavidin-coated Qdots labeled by antibody selectively targeted pathogenic E. coli O157:H7
Su and Li
51
E. coli O157
In vivo
Streptavidin-coated QDs conjugated to anti-E. coli O157 antibody
Yang and Li
52
E. coli O157∶H7
In vivo
QDs with different sizes conjugated to anti-E. coli O157 and anti-Salmonella antibodies
S. typhimurium
The bead-cell complexes reacted with QD-antibody conjugates to form bead-cell-QD complexes
1. QDs for assessing axon growth
A major health problem with injuries to the spinal cord and brain is traumatic central nervous system injury reporting of approximately 265,000 and 1.5 million new injuries each year
103
104
105
. QDs represent a new device of significant potential in neuroscience research, and they are useful for experiments that are limited by the restricted anatomy of neuronal and glial interactions
106
. One of the problems in treatment is estimating its effectiveness. They allow the ability to visualize and track dynamic molecular processes over long times (Figure 8)
106
. Application of surface-engineered QDs is an area of nanotechnology probing the details of cellular and molecular processes in neuronal cells
4
107
108
109
. QD bioconjugates based on surface chemistry can be broadly classified as follows: (1) QDs' surface modified by bioactive molecules and (2) QD-polymer nanocomposites
103
. This advance might be significantly important to assess axon growth pending the regeneration process
103
. Previous investigations were demonstrated in Table 2.
<p>Figure 8</p>Using QD conjugated with antibody for labeling of neurons and glia
Using QD conjugated with antibody for labeling of neurons and glia. (A) Labeled β-tubulin in primary cortical neurons. (B) Labeled glial fibrillary acidic protein in primary cortical astrocytes. (C) Labeled for β-tubulin in PC12 cells 106.
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<p>Table 2</p>
Applications of QDs in labeling neurons and glia cells
Authors
Type of QD used
Application of QD
Dahan et al.
61
QD-GlyR
Target neurons to investigate a specific neurophysiological process(QDs to track individual glycine receptors and analyze their lateral dynamics in the neuronal membrane)
Pathak et al.
106
Antibody-conjugated quantum dots
Performed the specific labeling of neurons and glia cells
Vu et al.
110
Tagged nerve growth factor (βNGF) to QDs
Investigate the QD nanostructure's potential to assess the neurite outgrowth
Sundara Rajan et al.
111
QD-anti-TrkA-TrkA receptor with transport by GFP
Immobilized QDs were conjugated with NGF, activate Trk receptors, and initiate neuronal differentiation in PC12 cells.
Howarth et al.
112
Tagged cell surface proteins with a specific peptide (acceptor protein) that can be directly biotinylated as a target for streptavidin-conjugated quantum dots
Specifically label and track AMPA receptors on cultured hippocampal neurons
Prasad et al.
113
Thioglycolic acid (TGA)-stabilized CdTe QDs
Performed imaging of PC12 cells
2. QD used as a probe in an anti-malarial drug-screening assay
Malaria is a major global health problem, threatening over 300 million people and causing nearly one million deaths annually
114
115
. Tokumasu et al. used QD-Ab to demonstrate the distinct pattern of distribution of protein and to observe erythrocyte membrane deformation occurring duringthe invasion of erythrocytes by Plasmodium falciparum
116
. Ku et al. showed a simple and efficient method to label P. falciparum-infected RBC using a QD-based probe and its applicability as an efficient probe for anti-malarial drug screening
115
.
Other applications
QDs as pH probes for the study of enzyme reaction kinetics
117
Lately, worth advancement has been achieved in water-soluble QDs as ionic probe. Jin et al. reported the use of modified CdSe QDs for the sensitive determination of cyanide ions [C ≡ N]−
117
118
. Xie et al. reported the determination of Cu2+ by using CdSe/ZnS QDs modified with bovine serum albumin
119
. QDs also have been reported to be sensitive to pH
120
121
122
123
124
125
. The sensitivity of QDs' photoluminescence to pH, improve stability, and a monitoring range for the determination of proton concentration, which is maybe due to a function of surface modifications and effects on exciton trap sites, leads to applications utilizing QDs as pH probes
126
. Water-soluble QDs, ZnS, modified with mercaptoacetic acid (MAA) were sensitive to environmental factors and found to be a satisfactory pH probes that could have potential applications in chemical and biochemical sensing. Using the modified QD surface, they were applied as pH probes in monitoring the hydrolysis of glycidyl butyrate which is catalyzed by porcine pancreatic lipase (PPL)
117
.
QDs use for protein micro- and nanoarrays to the detection of cancer biomarkers Protein microarrays are useful device as highthroughput screening tools in proteomics
127
128
129
, for biosensing purpose
130
, new drug discovery
131
, and enabling a quick parallel screening method for the detection of protein-protein interactions in case of large protein populations. There are various reports in which QDs have been used in microarray fabrication such as sandwich-based immunoassay type, RP protein microarray type, etc.
132
133
134
135
. Here, IgG detection was done on a glass chip using a QD-labeled secondary Abs as sandwich assay approach. In RP protein microarrays, Geho et al. used pegylated QDs conjugated with streptavidin as detection elements. In another study, Zajac et al. investigated the ability of the platform to detect different cytokines TNF-α, IL-8, IL-6, MIP-1β, IL-13, and IL-1β using two different models of quantum dot probes. Their results demonstrated high sensitivity of the investigated detection system with less than picomolar concentration
136
. Kerman et al. reported the use of QDs for detection cell lysates spiked with DNA-PK proteins with the help of mAb, in an RP protein microarray format. Kerman et al. make immunosensor based on QD for the detection of prostate specific antigen (PSA) in a sandwich assay approach for chip fabrication
134
. Gokarna et al. used pegylated QD-conjugated PSA Abs to demonstrate the fabrication of a cancer protein biochip for the detection of PSA, which is a biomarker for prostate cancer. The QD nonspecificity can show to be quite detrimental to some extent in case of multiplexed assay systems where multiple proteins are to be detected simultaneously
83
.
QD delivery Due to the unique properties of QDs, they are best tools for intracellular studies such as visualizing the cellular structure, studying the dynamic cellular processes, and tracking single molecules in the cell
137
138
. To achieve this goal, translocation of functionalized QDs into the cell for labeling organelles and tracking single molecules is important. QDs have hydrophobic surface and have a little toxicity, therefore cannot be applied in vivo unless their surface is modified. Thus, by surface modification, their hydrophilicity will increase but their toxicity will decrease.
Hasegawa et al. used nanogel-QD hybrid nanoparticles for live cell imaging
48
. They also confirmed the cellular uptake of CHPNH2(15)-QD nanoparticles using other normal cells (TIG-3 and MRC-5) and cancer cells (T24, Saos-2, T98G, A549, MCF-7, and YKG-1) (Figure 9)
48
.
<p>Figure 9</p>Confocal laser scanning fluorescence microscopyimages of cells labeled with CHPNH2(15)-QD nanoparticle
Confocal laser scanning fluorescence microscopyimages of cells labeled with CHPNH2(15)-QD nanoparticle. (A) TIG-3 cells, (B) MRC-5 cells, (C) MCF-7 cells, and (D) YKG-1 cells 48.
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In recent years, functional peptides that transmit biomaterials into cells have been developed in biomaterial research. Because of lysosomal trapping, QD delivery into cells with conjugated cell-penetrating peptides by the endocytic pathway was challenging in biomedical applications
139
. In another study, engineered peptides for producing QDs tagging protein ligands and biosensors to their surfaces, by appropriate cysteines or histidines, have served as ligands
140
. Encapsulation of QDs in viral capsids provides a new tool which allows the design of intracellular microscopic probes and vectors
141
. More samples of QD delivery systems are shown in Table 3.
<p>Table 3</p>
QD delivery systems
Authors
Delivery system of QD
Use
Jia et al.
142
Multiwalled carbon nanotube (MWNT) delivery system
MWNTs are containing antisense oligodeoxynucleotides and CdTe QDs via electrostatically layer-by-layer assembling.
Chen et al.
143
, Xue et al.
144
, Delehanty et al.
145
, Ruan et al.
146
, Wei et al.
147
Tat peptide-mediated delivery system
QDs conjugated to the cell-penetrating peptide derived from the human immunodeficiency virus-1 transactivator protein
Lagerholm et al.
148
Peptide delivery system
Nine residue biotinylated l-arginine peptide is used to enhance delivery of streptavidin-conjugated QDs into mammalian cells.
Bagalkot et al.
149
A10 RNA aptamer
Functionalizes the surface of QD with the A10 RNA aptamer, which recognizes the extracellular domain of the prostate specific membrane antigen
Bakalova et al.
150
Silica-shelled quantum dots
Based on silica-shelled single QD micelles with incorporated paramagnetic substances [tris(2,2,6,6-tetramethyl-3,5-heptanedionate)/gadolinium] into the micelle and/or silica coat
Yum et al.
151
Nanoscale mechanochemical method
Using a membrane-penetrating nanoneedle
Yuan et al.
152
Chitosan (N-acetylglucosamine) tumor-targeted drug delivery
QDs encapsulated with chitosan
Hasegawa et al.
48
Nanogel-QD hybrid
Nanogels of CHPNH 2 with 15 amino groups per 100 glucose units and QDs that were conjugated with protein A molecules were mixed.
Dixit et al.
141
Viral vectors
QDs encapsulation in viral capsids
Zhang and Liu
153
Nonviral vectors
Cappingthe surface of ZnO QD with poly(2-(dimethylamino) ethyl methacrylate)
Jablonski et al.
154
Cationic peptide and a hydrophobic counterion
Quantum dots have been delivered to the cytosol of living cells using a combination of a cationic peptide, polyarginine, and a hydrophobic counterion, pyrenebutyrate.
Qi and Gau
155
QD-amphipol nanocomplex
Advantages include cytoplasm delivery and endosome escape.
Gao et al.
109
Polymeric delivery system
The structural design involves encapsulating QDs with an ABC triblock copolymer and linking this amphiphilic polymer.
Duan and Nie
77
Polymeric delivery system
QDs were encapsulated by PEI-g-PEG.