Abstract:Fluorescent semiconductor quantum dots (QDs) have attracted tremendous attention over the last decade. The superior optical properties of QDs over conventional organic dyes make them attractive labels for a wide variety of biomedical applications, whereas their potential toxicity and instability in biological environment has puzzled scientific researchers. Much research effort has been devoted to surface modification and functionalization of QDs to make them versatile probes for biomedical applications, and si… Show more
“…The superior optical and electronic properties of QDs over conventional organic dyes, such as high brightness, high photostability, continuous absorption, narrow emission bandwidth, and the ability to simultaneously excite multiple fluorescent colors, make them attractive labels for the development of QDs-IHC imaging for multiplexing cancer biomarker detection on FFPE tissues. 24,25 In our study, we confirmed that QDs-IHC is a simple and standardized method for detecting EGFR mutations, and it has high sensitivity and specificity when compared with real-time PCR. In addition, the development of specific antibodies against EGFR mutation proteins might be useful for the diagnosis and treatment of lung cancer.…”
Background
Epidermal growth factor receptor (EGFR) mutation status plays an important role in therapeutic decision making for non-small cell lung cancer (NSCLC) patients. Since EGFR mutation-specific antibodies (E746-A750del and L858R) have been developed, EGFR mutation detection by immunohistochemistry (IHC) is a suitable screening test. On this basis, we want to establish a new screening test, quantum dots immunofluorescence histochemistry (QDs-IHC), to assess
EGFR
gene mutation in NSCLC tissues, and we compared it to traditional IHC and amplification refractory mutation system (ARMS).
Materials and methods
EGFR
gene mutations were detected by QDs-IHC, IHC, and ADx-ARMS in 65 cases of NSCLC composed of 55 formalin-fixed, paraffin-embedded specimens and ten pleural effusion cell blocks, including 13 squamous cell carcinomas, two adenosquamous carcinomas, and 50 adenocarcinomas.
Results
Positive rates of EGFR gene mutations detected by QDs-IHC, IHC, and ADx-ARMS were 40.0%, 36.9%, and 46.2%, respectively, in 65 cases of NSCLC patients. The sensitivity of QDs-IHC when detecting EGFR mutations, as compared to ADx-ARMS, was 86.7% (26/30); the specificity for both antibodies was 100.0% (26/26). IHC sensitivity was 80.0% (24/30) and the specificity was 92.31% (24/26). When detecting EGFR mutations, QDs-IHC and ADx-ARMS had perfect consistency (
κ
=0.882;
P
<0.01). Excellent agreement was observed between IHC and ADx-ARMS when detecting EGFR mutations (
κ
=0.826;
P
<0.01).
Conclusion
QDs-IHC is a simple and standardized method to detect EGFR mutations with its high sensitivity and specificity, as compared with real-time polymerase chain reaction. In addition, the development of specific antibodies against EGFR mutation proteins might be useful for the diagnosis and treatment of lung cancer.
“…The superior optical and electronic properties of QDs over conventional organic dyes, such as high brightness, high photostability, continuous absorption, narrow emission bandwidth, and the ability to simultaneously excite multiple fluorescent colors, make them attractive labels for the development of QDs-IHC imaging for multiplexing cancer biomarker detection on FFPE tissues. 24,25 In our study, we confirmed that QDs-IHC is a simple and standardized method for detecting EGFR mutations, and it has high sensitivity and specificity when compared with real-time PCR. In addition, the development of specific antibodies against EGFR mutation proteins might be useful for the diagnosis and treatment of lung cancer.…”
Background
Epidermal growth factor receptor (EGFR) mutation status plays an important role in therapeutic decision making for non-small cell lung cancer (NSCLC) patients. Since EGFR mutation-specific antibodies (E746-A750del and L858R) have been developed, EGFR mutation detection by immunohistochemistry (IHC) is a suitable screening test. On this basis, we want to establish a new screening test, quantum dots immunofluorescence histochemistry (QDs-IHC), to assess
EGFR
gene mutation in NSCLC tissues, and we compared it to traditional IHC and amplification refractory mutation system (ARMS).
Materials and methods
EGFR
gene mutations were detected by QDs-IHC, IHC, and ADx-ARMS in 65 cases of NSCLC composed of 55 formalin-fixed, paraffin-embedded specimens and ten pleural effusion cell blocks, including 13 squamous cell carcinomas, two adenosquamous carcinomas, and 50 adenocarcinomas.
Results
Positive rates of EGFR gene mutations detected by QDs-IHC, IHC, and ADx-ARMS were 40.0%, 36.9%, and 46.2%, respectively, in 65 cases of NSCLC patients. The sensitivity of QDs-IHC when detecting EGFR mutations, as compared to ADx-ARMS, was 86.7% (26/30); the specificity for both antibodies was 100.0% (26/26). IHC sensitivity was 80.0% (24/30) and the specificity was 92.31% (24/26). When detecting EGFR mutations, QDs-IHC and ADx-ARMS had perfect consistency (
κ
=0.882;
P
<0.01). Excellent agreement was observed between IHC and ADx-ARMS when detecting EGFR mutations (
κ
=0.826;
P
<0.01).
Conclusion
QDs-IHC is a simple and standardized method to detect EGFR mutations with its high sensitivity and specificity, as compared with real-time polymerase chain reaction. In addition, the development of specific antibodies against EGFR mutation proteins might be useful for the diagnosis and treatment of lung cancer.
“…It is a challenge to study the in vivo biodistribution and toxicology of quantum dots in animal systems that could potentially mimic its toxicity in human use. In future, fabrication of biocompatible, non-immunogenic, ultra-small size (<5.0 nm) quantum dots for nanomedicine loading that would be excreted through a renal clearance mechanism is highly awaited 21, 138, 139. Carbon nanotubes exert potential to cause toxicities in vivo and in vivo .…”
Nanotheranostics is to apply and further develop nanomedicine strategies for advanced theranostics. This review summarizes the various nanocarriers developed so far in the literature for nanotheranostics, which include polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles, carbon nanotubes, and nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents for better theranostic effects with fewer side effects. The theranostic nanomedicine can achieve systemic circulation, evade host defenses and deliver the drug and diagnostic agents at the targeted site to diagnose and treat the disease at cellular and molecular level. The therapeutic and diagnostic agents are formulated in nanomedicine as a single theranostic platform, which can then be further conjugated to biological ligand for targeting. Nanotheranostics can also promote stimuli-responsive release, synergetic and combinatory therapy, siRNA co-delivery, multimodality therapies, oral delivery, delivery across the blood-brain barrier as well as escape from intracellular autophagy. The fruition of nanotheranostics will be able to provide personalized therapy with bright prognosis, which makes even the fatal diseases curable or at least treatable at the earliest stage.
“…In recent years, tremendous effort has been made to develop theranostic agents by bringing together the therapeutic and imaging components to synthesize a single molecule as well as by constructing nanoparticles and macromolecules loaded with those two components . The development of multimodal systems using various platforms such as fluorescent‐based drug delivery, drug–polymer conjugates, polymeric/magnetic/metal nanoparticles, dendrimers, liposomes, micelles, and carbon nanomaterials are some examples of those efforts. We and others have reported the modification of known therapeutics with common imaging agents such as DOTA .…”
Conventional one-bead one-compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built-in imaging component for a certain target is a daunting task, and structure-based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule. Such molecules in the library can be used to screen, identify, and validate as direct theranostic candidates against targets of interest. As the first step in achieving that aim, we developed an on-bead library of 153,600 Peptoid-DOTA compounds in which the peptoids are the target-recognizing and potentially therapeutic components and the DOTA is the imaging component. We attached the DOTA scaffold to TentaGel beads using one of the four arms of DOTA, and we built a diversified 6-mer peptoid library on the remaining three arms. We evaluated both the synthesis and the mass spectrometric sequencing capacities of the test compounds and of the final library. The compounds displayed unique ionization patterns including direct breakages of the DOTA scaffold into two units, allowing clear decoding of the sequences. Our approach provides a facile synthesis method for the complete on-bead development of large peptidomimetic-DOTA libraries for screening against biological targets for the identification of potential theranostic agents in the future.
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