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Minimal Cytotoxicity of Water-Soluble SiQDs with Blood Plasma Proteins Interaction

Prof. C. Shanmugavel et al., and his research collaboration team (from various universities at Japan) have been investigated on the interaction of blood plasma proteins and water-soluble silicon quantum dots (SiQDs) for the minimal cytotoxicity. This research investigation was reported in nanomaterials of MDPI publication journal and published on 13th November 2020. In this research article, they have reported on the conformational changes of blood plasma proteins during the interaction with near-infrared light-emitting nanoparticles, which comprised with assembled Pluronic-F127 coated semiconductor (silicon) QDs terminated with decane monolayers. 

The semiconductor QDs have chosen as an alternative, owing to its high quantum yield and low photo bleaching characters by various researchers and scientists. Other previous research studies have also showed that the QDs has exhibited a molecular interaction with various proteins, which consists of toxic heavy metal ions (like mercury selenium, lead, cadmium). Hence, they have found the water soluble semiconductor QDs possess for the molecular interactions without any toxic ions. Water-soluble semiconductor QDs are found to be in contact with our blood stream that is very essential for the biological applications. It also includes the biomarkers, who are working for the first therapeutic spectral window with deep tissue imaging for better understanding of the compatibility with blood stream [1]. 

Silicon (Si) is the semiconducting element that have present in the water-soluble semiconductor QDs, which is widely used for the various device applications and industries due to its environmentally friendly, inert, non-toxic and abundant. Therefore, SiQDs are found to be suitable for developing the class of quantum materials, owing to its superior optical properties, tunability of the photoluminescence (PL) peak wavelength for the biological applications [1]. 

Human blood plasma were composed of specific functionalities enriched with thousands of proteins. As per Human Proteome Organization, it can be identified that about 89% of proteins were detected from 21,842 plasma proteins. Among them, only 10% have been utilized and measured quantitatively. In general, our human blood consists of high molecular weight proteins (such as albumin and globulin), which detect the low molecular weight proteins. The main essential proteins that are present in our human blood plasma are Albumin, Fibrinogen, and Transferrin, respectively. However, the most abundant protein (55%) in the blood plasma is the Albumin, which involves delivering fatty acids, and transporting nutrients, steroids with several therapeutic drugs [2]. 

The main three plasma proteins (Albumin, Fibrinogen, and Transferrin) were chosen during the meet of nanoparticles with SiQDs to investigate its morphological changes. When the nanoparticles enters in to the bloodstream, then there will be an interaction of biomolecules for the formation of bio-corona, such as protein corona, on its surfaces. These interaction of blood plasma proteins plays a major significant role on the development of nanoparticles for the drug delivery applications [3, 4].

Hadjidemetriou et al. [3] have reported that an inner layer with tightly bound proteins is termed as ‘hard corona,’ while an outer rapidly exchanging layer with weakly bound proteins is termed as ‘soft corona.’ Also, both the albumin and transferrin have exhibited higher quenching constants (1011th order) that leads to stronger association of hard protein corona formation. Meanwhile, the fibrinogen have a lower (1010th order) quenching constant, of soft protein corona formation.

Scheme 1. The Schematic diagram of synthesized Pluronic-F127 with functionalized decyl-coated silicon quantum dots (SiQD-De) nanoparticles and protein corona formation assumption [1].  
Water-Soluble Nanoparticle Synthesis of SiQDs: 

Based upon the scheme, they have prepared a waterborne particles, which consists of a Pluronic F127 core shell, assembled with SiQDs terminated apart from the decane monolayers. The preparation of hydrogen-terminated QDs were carried out using the thermal disproportionation method of the TES hydrolysis product, followed by subsequent hydrofluoric acid etching. By optimizing the reaction temperature and hydrofluoric acid etching, the QDs diameters were been controlled, due to its diamond cubic lattice structure. Further, the QDs termination with decane monolayers were carried out using thermal hydrosilylation of 1-decane to yield the product SiQD-De.

Interaction between Nanoparticles and Plasma Proteins: 
The molecular interaction between the SiQD-De/F127 nanoparticles and the plasma proteins were monitored using UV-vis spectrometry. Further, they reported that the addition of nanoparticles (about 0–2 µg/mL) have influenced the spectral properties of plasma proteins were in the range of 190–400 nm. These changes in the absorption were recorded, which can attributed to emerging effect of polar solvents like water. Around the aromatic amino acid residues of proteins (i.e., phenylalanine, tryptophan, and tyrosine), the perturbation of the micro environment occurs. 

A concern protein-nanoparticle interactions results to the conformational changes or denaturation of proteins adsorbed to the nanoparticles. Hence, such conformational changes and its further investigations revealed that even after the interaction, the protein can realize its regular biological activity [5]. 

Our SNB team have emphasize this research article to enrich our viewer’s knowledge to understand the following four points with minimal cytotoxicity. (i) An interaction of water-soluble silicon quantum dots and blood plasma proteins. (ii) Biocompatible SiQDs/F127 nanoparticles were successfully synthesized using Pluronic F127. (iii) The continuous observation of the optical absorption and emission properties of proteins with addition of nanoparticles. (iv) The interesting phenomena that can be identified was the ‘plasma proteins’ binding parameters were mainly depends upon the interaction between the protein binding surface and the nanoparticles. But, it is a deserving attention that the conformational changes are identified only for fibrinogen and transferrin, which suggests that the nanoparticle do not influence the ordered structure of proteins to the bloodstream. Hence, this research team and their report have recommended the basis for the QDs designing without altering the biomacromolecules of original conformation that enable the cellular uptake with minimal cytotoxicity. 

References 
  1. C. Shanmugavel, et al., Nanomaterials, 10, 2250 (2020). 
  2. Y. K. Paik, et al., J. Proteome Res. 17, 4023 (2018). 
  3. M. Hadjidemetriou et al., Nat. Nanotechnol.12, 288 (2017). 
  4. V. P. Vu, et al., Nat. Nanotechnol. 14, 260 (2019).
  5. S.Qu, et al., Small, 16, 1907633 (2020). 

--- Dr. Y. Sasikumar

School of Materials Science and Engineering, 

Tianjin University of Technology, China

Email:sasikumar.phd@gmail.com

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