Cancer Cell Targeting Using Folic Acid/Anti-HER2 Antibody Conjugated Fluorescent CdSe/CdS/ZnS-Mercaptopropionic Acid and CdTe-Mercaptosuccinic Acid Quantum Dots

Abstract

CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.

Protein Design for the Synthesis and Stabilization of Highly Fluorescent Quantum Dots

“…Nevertheless, these new expensive methods produce QDs that still display low biocompatibility and low stability under physiological conditions. Several chemical procedures based on biological reagents and mild reaction conditions have been developed during recent years. − In addition, these procedures have contributed to improve the biocompatibility of QDs. However, the quality, in terms of PL intensity, of the fluorescent QDs synthesized by these simpler and eco-friendly methods decreases in comparison with those obtained by the traditional organic chemical route. ,,, …”

“…4 Nevertheless, these methodologies produce QDs that still display low biocompatibility, sensitivity to pH and high ionic strength, as well as elevated production costs. [18][19][20] An alternative approach to template and stabilize QDs is to use peptides and proteins with high affinity for transition metals. [21][22][23] In nature, peptides rich in cysteines and glutamic acids, for example, phytochelatins participate in the packaging and export of toxic cadmium as less harmful cadmium sulphide (CdS) nanocrystals.…”

“…A wide range of organic molecules have been evaluated as capping agents, for example, organic thiols, including biological molecules, for example, cysteine, glutathione, amine-rich dendrimers, and polyphosphates . Nevertheless, these methodologies produce QDs that still display low biocompatibility, sensitivity to pH, and high ionic strength, as well as elevated production costs. − An alternative approach to template and stabilize QDs is to use peptides and proteins with high affinity for transition metals. − In nature, peptides rich in cysteines and glutamic acids, for example, phytochelatins, participate in the packaging and export of toxic cadmium as less harmful cadmium sulfide (CdS) nanocrystals . Taking inspiration from biological strategies, peptide-assisted synthesis of QDs has become a promising method to grow semiconducting nanocrystals − and some examples have been reported on protein–QDs hybrids prepared by the direct synthesis of QDs in aqueous solution. ,,,− Proteins, such as BSA, lysozyme, trypsin, hemoglobin, transferrin, and poly histidine fusion proteins have been used for the synthesis of protein–QDs hybrids. ,,− However, the change of the established organic routes to more sustainable aqueous routes results in significantly decreased fluorescence quantum yields (QY). ,,, Therefore, it is still challenging to produce biocompatible highly fluorescent QDs for biomedical applications.…”

Bio-Conjugated Quantum Dots for Cancer Research: Detection and Imaging

“…These FAPEG-TNGs exhibited good biocompatibility, nuclear uptaking, and cancer cell targeting. Furthermore, Singh G et al conjugated fluorescent CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) with FA, which showed higher cellular internalization (43). Similarly, Salova AV et al constructed EGF-QDs complex by the biotin-streptavidin system (bEGF-savQDs) that can enter Hela cells via temperature-dependent clathrin-mediated EGFR specific pathway (43).…”

Stimuli‐responsive nanotherapeutics for precision drug delivery and cancer therapy

“…Folic acid has high affinity toward this type of receptor; thus, this small molecule is commonly used to modify therapeutic nanoparticles, enabling the selective delivery of encapsulated drugs to malignant cells in human cancer patients (Kim et al, ). With the use of proper linkers, folate‐decorated nanoparticles can be readily internalized into tumor cells, exerting potently cytotoxic effects (Singh et al, ). In one instance, biodegradable polymeric micelles (i.e., PEG‐PLGA) coupled to folate were prepared for active delivery of DOX, and the results showed an increased amount of DOX accumulating in tumor tissues and a significant regression of the tumor volume after systemic administration of these micelles (Yoo & Park, ).…”