Abstract
Nanoparticles are efficient drug delivery vehicles for targeting specific organs as well as systemic therapy for a range of diseases, including cancer. However, their interaction with the immune system offers an intriguing challenge. Due to the unique physico-chemical properties, carbon nanotubes (CNTs) are considered as nanocarriers of considerable interest in cancer diagnosis and therapy. CNTs, as a promising nanomaterial, are capable of both detecting as well as delivering drugs or small therapeutic molecules to tumour cells. In this study, we coupled a recombinant fragment of human surfactant protein D (rfhSP-D) with carboxymethyl-cellulose (CMC) CNTs (CMC-CNT, 10–20 nm diameter) for augmenting their apoptotic and immunotherapeutic properties using two leukemic cell lines. The cell viability of AML14.3D10 or K562 cancer cell lines was reduced when cultured with CMC-mwCNT-coupled-rfhSP-D (CNT + rfhSP-D) at 24 h. Increased levels of caspase 3, 7 and cleaved caspase 9 in CNT + rfhSP-D treated AML14.3D10 and K562 cells suggested an involvement of an intrinsic pathway of apoptosis. CNT + rfhSP-D treated leukemic cells also showed higher mRNA expression of p53 and cell cycle inhibitors (p21 and p27). This suggested a likely reduction in cdc2-cyclin B1, causing G2/M cell cycle arrest and p53-dependent apoptosis in AML14.3D10 cells, while p53-independent mechanisms appeared to be in operation in K562 cells. We suggest that CNT + rfhSP-D has therapeutic potential in targeting leukemic cells, irrespective of their p53 status, and thus, it is worth setting up pre-clinical trials in animal models.
Highlights
The innate immune system plays a key role in the clearance of pathogens and synthetic compounds including nanoparticles [1,2]
This study was aimed at examining the ability of carbon nanotubes (CNTs) + recombinant fragment of human surfactant protein D (rfhSP-D) to induce apoptosis using an eosinophilic cell line, AML14.3D10 [28], and a chronic myelogenous leukemia cell line, K562, to assess if CNT + rfhSP-D nanomaterials are worth testing in animal models
The quantitative analysis of viability in treated leukemic cells was carried out using trypan blue (Figure 2) and MTT (Figure 3) assays at 24 h time point
Summary
The innate immune system plays a key role in the clearance of pathogens and synthetic compounds including nanoparticles [1,2]. Human surfactant protein D (SP-D) is a humoral, pathogen pattern recognition molecule, which is found to be associated with pulmonary surfactant, as well as mucosal surfaces outside the lungs [12,13]. SP-D belongs to the collectin family, a collagen containing C-type (calcium-dependent) lectin [14]. The primary structure of SP-D comprises a cross-linking amino-terminal region, a triple-helical collagen region, a coiled-coil neck region, and a C-type lectin domain or carbohydrate recognition domain (CRD) as a trimeric unit [15,16]. SP-D can bind to various carbohydrate and/or charge patterns on the surface of pathogens and become involved in clearing them by recruiting phagocytic cells such as neutrophils and macrophages [15,16]. A truncated form of recombinant human SP-D (rfhSP-D), composed of trimeric neck and
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