Surface modification of hollow gold nanoparticles conducted by incorporating cancer cell membrane and AS1411 aptamer, aiming to achieve a dual-targeted therapy for colorectal cancer.

Due to its inherent membrane structure, a nanostructure enveloped by an active cell membrane possesses distinctive characteristics such as prolonged presence in the bloodstream, precise identification capabilities, and evasion of immune responses. This research involved the production of biomimetic nanoparticles, specifically hollow gold nanoparticles (HGNPs) loaded with methotrexate (MTX), which were further coated with cancer cell membrane. These nanoparticles were then adorned with AS1411 aptamer to serve as a targeting agent (Apt-CCM-HG@MTX). The nanoplatform demonstrated precise targeting towards cancer cells due to its dual-targeting characteristic (AS1411 aptamer and C26 cancer cell membrane), exhibiting uniformity in distribution. It also displayed a desirable response to photothermal stimulation, controlled release of drugs, and exceptional properties for fluorescence imaging. The system was composed of spherical HGNPs measuring 51.33 ± 5.70 nm in diameter, which were effectively loaded with MTX using a physical absorption method. The encapsulation efficiency achieved was recorded at 79.54 %, while the loading efficiency reached 38.21 %. The targeted formulation demonstrated a noteworthy mortality of approximately 45 % in the nucleolin positive cell line, C26, as determined by in vitro cytotoxicity assays. As a result of the functionalization process applied to the homologous binding adhesion molecules found in cancer cell membranes and targeting ability of AS1411 aptamer, Apt-CCM-HG@MTX demonstrated a substantial enhancement in targeting tumors and facilitating cellular uptake during in vivo experiments. Furthermore, under NIR radiation the photothermal effect exhibited by Apt-CCM-HG@MTX in the tumor area was notably robust due to the distinctive attributes of HGNPs. The conclusions obtained from this study have the potential to assist in adopting a bioinspired strategy that will significantly improve the effective management of MTX and therapy for individuals with colorectal cancer.

Application of green-synthesized carbon dots for imaging of cancerous cell lines and detection of anthraquinone drugs using silica-coated CdTe quantum dots-based ratiometric fluorescence sensor.

Chemotherapy drugs of daunorubicin and doxorubicin treat cancers with many side effects. So, detection of them in the biological system for regulation and controlling of usage is essential. In this study, a ratiometric fluorescent method was introduced for detection of daunorubicin and doxorubicin using bell pepper-based carbon dots, as the variable signal, and silica-coated CdTe quantum dots, as the constant signal. The detection was done based on variations of carbon dots intensity in the presence of drugs in comparison with the constant intensity of silica-coated CdTe quantum dots. The proposed ratiometric fluorescent method was successfully used for detection of daunorubicin and doxorubicin range of 54.37-13594.34 nmolL-1 and 86.2-17242 nmolL-1, with a detection limit of 18.53 nmolL-1 and 29 nmolL-1, respectively. Also, this method was used for detection of drugs in serum samples with recovery ranges of 86.14-99.62 (RSD 3-1.47%) and 86.32-97.53 (3.38-1.48%), respectively. Finally, after evaluation of carbon dots toxicity by MTT test, carbon dots was applied for imaging of prostate cancer cell lines (PC-3) and breast cancer cell lines (MCF7). The results demonstrated that despite improvement of the repeatability and interferences reduction by ratiometric method, also carbon dots were successfully applied for imaging of cell lines.

A multi-storey DNA nanostructure containing doxorubicin and AS1411 aptamer for targeting breast cancer cells.

Herein, we presented a novel DOX-loaded multi-storey DNA nanostructure, including AS1411 aptamer as a targeting agent for treatment of target cells (MCF-7 and 4T1). Gel retardation test and fluorometric analysis were used to examine the construction of DNA nanostructure and loading of DOX in the complex. At pH 5.5 and 7.4, the release patterns of DOX from the prepared formulation were studied. Cell viability test was conducted to analyse the cell cytotoxicity ability of the DOX loaded multi-storey DNA nanostructure compared to free DOX in 4T1, MCF-7 (target) and CHO cells (non-target). Flow cytometry analysis was used to examine the DOX-loaded DNA nanostructure internalisation. Finally, the developed DOX-loaded multi-storey DNA nanostructure was tested in vivo to see if it could prevent tumour growth. The drug was released from the nanocomplex in a pH-related process (higher release in acidic pH compared to neutral pH). According to MTT assay, DOX-loaded DNA nanostructure damaged nucleolin positive cells while not significantly affecting nucleolin negative cells. The formulation was efficaciously internalised into target cells (4T1 and MCF-7), but not into non-target ones. Moreover, DOX-loaded DNA nanostructure can restrict tumour growth, increase survival rate, and accumulate significantly more in the tumour site than free DOX.

A highly sensitive fluorescent aptasensor for detection of prostate specific antigen based on the integration of a DNA structure and CRISPR-Cas12a.

Herein, a facile fluorescent CRISPR-Cas12a-based sensing strategy is presented for prostate specific antigen (PSA), as a prostate cancer biomarker, with the assistance of a cruciform DNA nanostructure and PicoGreen (PG) as a fluorochrome. Highly sensitive recognition of PSA is one of the virtues of the proposed method which comes from the use of unique features of both CRISPR-Cas12a and DNA structure in the design of the aptasensor. The presence of PSA creates a cruciform DNA nanostructure in the sample which can be loaded by PG and make sharp fluorescence emission. While, when there is no PSA, the CRISPR-Cas12a digests sequences 1 and 3 as single-stranded DNAs, causing no DNA structure and a negligible fluorescence is detected after addition of PG. This aptasensor presents a sensitive recognition performance with detection limit of 4 pg/mL and a practical use for determination of PSA in serum samples. So, this analytical strategy introduces a convenient and highly sensitive approach for detection of disease biomarkers.

Identification and imaging of leukemia cells using dual-aptamer-functionalized graphene oxide complex.

Acute lymphoblastic leukemia is the most common malignancy in children. Patient improvement completely depends on the diagnosis of acute lymphoblastic leukemia. So there is a great demand for diagnosis of acute lymphoblastic leukemia. In this study, a novel assay based on dual-aptamer (Sgc8c and ATP aptamers)-functionalized graphene oxide (DAFGO) complex was designed for the identification of Molt-4 cells (human acute lymphoblastic leukemia T-cell). This assay relies on the internalization of DAFGO complex into Molt-4 cells, but not into U266 cells, using Sgc8c aptamer as molecular recognition probe, and release of FAM-labeled ATP aptamer from the complex in the presence of high amounts of ATP in lysosome, leading to a strong fluorescence emission. Formation of DAFGO complex was analyzed by fluorometric analysis and gel retardation assay. The internalization of complex was monitored by flow cytometry and fluorescence microscopy in Molt-4 (target) and U266 cells (nontarget) with DAFGO complex. Our results showed that the developed complex was efficiently internalized into target cells and induced a strong fluorescence emission.