Cytotoxicity, fluorescence tagging and gene-expression study of CuInS/ZnS QDS - meso (hydroxyphenyl) porphyrin conjugate against human monocytic leukemia cells

Abstract

The toxicity of heavy metals present in binary semiconductor nanoparticles also known as quantum dots (QDs) has hindered their wide applications hence the advent of non-toxic ternary quantum dots. These new group of quantum dots have been shown to possess some therapeutic action against cancer cell lines but not significant enough to be referred to as an ideal therapeutic agent. In this report, we address this problem by conjugating red emitting CuInS/ZnS QDs to a 5,10,15,20-tetrakis(3hydroxyphenyl)porphyrin-photosensitizer for improved bioactivities. The glutathione capped CuInS/ ZnS QDs were synthesized in an aqueous medium using a kitchen pressure cooker at different Cu: In ratios (1:4 and 1:8) and at varied temperatures (95 °C, 190 °C and 235 °C). Optical properties show that the as-synthesized CuInS/ZnS QDs become red-shifted compared to the core (CuInS) after passivation with emission in the red region while the cytotoxicity study revealed excellent cell viability against normal kidney fibroblasts (BHK21). The highly fluorescent, water-soluble QDs were conjugated to 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) via esterification reactions at room temperature. The resultant water-soluble conjugate was then used for the cytotoxicity, fluorescent imaging and gene expression study against human monocytic leukemia cells (THP-1). Our result showed that the conjugate possessed high cytotoxicity against THP-1 cells with enhanced localized cell uptake compared to the bare QDs. In addition, the gene expression study revealed that the conjugate induced inflammation compared to the QDs as NFKB gene was over-expressed upon cell inflammation while the singlet oxygen (1 o 2) study showed the conjugate possessed large amount of 1 o 2 , three times than the bare porphyrin. Thus, the as-synthesized conjugate looks promising as a therapeutic agent for cancer therapy. The use of nanomaterials for biological application has in the past decade transpired as a promising avenue to explore for biological application due to their size, shape, specific surface area, aspect ratio and surface chemistry. Of the reported nanomaterial, semiconductor nanomaterials also known as quantum dots (QDs) still remain the most promising due to their excellent optoelectronic properties and spectral tunability which allows for their use in the ultraviolet and near infra-red region 1,2. These inherent properties have made QDs more appealing

Aqueous Synthesis of DNA-Functionalized Near-Infrared AgInS2/ZnS Core/Shell Quantum Dots

“…Therefore, growing efforts are devoted to the development of biocompatible and toxic heavy metal-free QDs. [7][8][9][10][11] Among them, ternary I-III-VI chalcopyrite-type materials are becoming the focus of interest. [12][13][14] These ternary QDs, regarded as promising eco-friendly materials for multiple applications, display a direct band gap (1.04-1.87 eV in the bulk materials) and high absorption coefficients (10 4 -10 5 cm -1 ).…”

The Photoluminescence and Biocompatibility of CuInS2-Based Ternary Quantum Dots and Their Biological Applications

“…Hence, the search for alternative methods is imperative. QDs with desired properties can be achieved by the varying the composition, ratio of the metal precursors, capping agent/stabilizers, type of stabilizers/capping agent, synthesis temperature, post-synthetic modification and passivation shells [8,18,[19][20][21][22]28,32,38,40,44]. Table 1.…”

“…Proper control over composition can lead to the formation of a different crystal structure (cubic to wurtzite structure) [28][29][30][31]. Several reports have been published on the synthesis of CIS NCs such as synthesis in solid phase [32,33], hydrothermal (including pressure cooker) [18,[34][35][36][37], decomposition of single-source precursors [28,[38][39][40][41] and the hot injection [42][43][44][45] method (Table 1). Hirpo et al [46] reported the conversion of (Ph 3 P) 2 CuIn(SEt) 4 and (Ph 3 P) 2 CuIn(SBu) 4 to CIS NCs.…”

“…To improve the PL emission of the CIS QDs, the most common strategies employed are the coating of shells and alloying strategies [13][14][15]18,42,43,55,56,58,59,61,65,66,[68][69][70]72,74,75,78,[87][88][89][90]. Earlier studies revealed that stoichiometry control is important in obtaining highly luminescent CIS QDs [20,21].…”

“…This increase was attributed to the fluorescence resonance energy transfer (FRET) between be the QDs and the porphyrin. Recently, our group reported the conjugation of meso-tetra-(4-sulfonatophenyl) porphyrin (TPPS4) and meso (hydroxyphenyl) porphyrin to the CIS/ZnS QD conjugate in order to improve the singlet oxygen generation of the porphyrin for multimodal imaging and therapy [18,117]. The cytotoxicity of CIS/ZnS and the TPPS4-CIS/ZnS conjugate was evaluated on a normal cell line (BHK 21) and a cancer cell line (THP-1).…”