Kinds Of Cancer Cells Research Articles

The role of Frequency Modulation in the Magic Light Anti-Cancer Therapy

The role of frequency modulation in the Magic Light anti-cancer therapy was investigated both in theory and in clinical trials. The existence of at least four different optimal modulation frequencies is required for cancer treatment. This was disclosed and is explained by the presence of at least of four different kinds of cancer cells within the same cancer, whereby each cancer cell type has its own speed of proliferation. The application of several different frequencies for cancer treatment in turn, during each treatment session, thus allows the Magic Light therapy to cure any type of cancer faster and completely.

PH sensitive adriamycin-incorporated nanoparticles self-assembled from amphiphilic chitosan derivatives with enhanced antioxidant and antitumor activities

Development of secure and efficient drug delivery systems to overcome physicochemical challenges in cancer clinical treatment is one of the most active fields, and novel drug carriers are actively sought. In this work, the successful synthesis of amphiphilic chitosan derivatives containing pyridine cations and folic acid (TMACMCF) was confirmed by FTIR and 1H NMR spectroscopy. The critical micelle concentration (CMC) of TMACMCF was studied, and the results indicated that it possessed a relatively low CMC (0.186 mg/mL). Self-assembled nanoparticles (TMACMCF-ADM NPs) for the entrapment and delivery of adriamycin (ADM) were synthesized based on TMACMCF, and the morphology, particle size, zeta potential, sustained release performance, antioxidant and antitumor activities, and cytotoxicity were investigated. The particle size of TMACMCF-ADM NPs was 163.79 ± 7.31 nm, and the morphology observed by SEM and TEM showed spherical or oval particles. TMACMCF-ADM NPs showed excellent entrapment of ADM with entrapment efficiency and drug loading efficiency of 65.04 ± 1.20 % and 22.73 ± 0.40 %, respectively. The release performance results showed that in vitro release profiles of ADM from NPs exhibited pH-sensitive controlled and sustained release properties. The assay of antioxidant activity exhibited that TMACMCF-ADM NPs possessed significantly improved scavenging ability against three kinds of radicals (Superoxide-radical, DPPH radical, and ABTS radical). Moreover, the assay of antitumor activity by CCK-8 test exhibited that nanoparticles led to statistically significant enhancement in inhibition index for four kinds of cancer cells (BGC-823, MCF-7, HEPG-2, and A549). This work provides a promising carrier for secure and effective entrapment and delivery of ADM.

Limonin inhibits the stemness of cancer stem-like cells derived from colorectal carcinoma cells potentially via blocking STAT3 signaling.

Limonin is one of the most abundant active ingredients of Tetradium ruticarpum. It exerts antitumor effects on several kinds of cancer cells. However, whether limonin exerts antitumor effects on colorectal cancer (CRC) cells and cancer stem-like cells (CSCs), a subpopulation responsible for a poor prognosis, is unclear. To evaluate the effects of limonin on CSCs derived from CRC cells. CSCs were collected by culturing CRC cells in serum-free medium. The cytotoxicity of limonin against CSCs and parental cells (PCs) was determined by cholecystokinin octapeptide-8 assay. The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability. As expected, limonin exerted inhibitory effects on CRC cell behaviors, including cell proliferation, migration, invasion, colony formation and tumor formation in soft agar. A relatively low concentration of limonin decreased the expression stemness hallmarks, including Nanog and β-catenin, the proportion of aldehyde dehydrogenase 1-positive CSCs, and the sphere formation rate, indicating that limonin inhibits stemness without presenting cytotoxicity. Additionally, limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice. Moreover, limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression. Inhibition of Nanog and β-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2 μmol/L colievlin. Taken together, these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.

IL-32 production from lung adenocarcinoma cells is potentially involved in immunosuppressive microenvironment.

Interleukin 32 (IL-32) is a proinflammatory cytokine secreted from several kinds of cancer cells. In the present study, we investigated the significance of IL-32 in lung adenocarcinoma by immunohistochemistry and bioinformatics analysis. IL-32 was positive in cancer cells of 21 cases (9.2%) of total 228 cases. Increased IL-32 gene expression was linked to worse clinical course in TCGA analysis, however, IL-32 expression in immunohistochemistry was not associated to clinical course in our cohort. It was also found that high IL-32 expression was seen in cases with increased lymphocyte infiltration. In vitro studies indicated that IFN-γ induced gene expression of IL-32 and PD1-ligands in lung adenocarcinoma cell lines. IL-32, especially IL-32β, also induced overexpression of PD1-ligands in human monocyte-derived macrophages. Additionally, Cancer-cell-derived IL-32 was elevated by stimulation with anticancer agents. In conclusion, IL-32 potentially induced by inflammatory conditions and anticancer therapy and contribute to immune escape of cancer cells via development the immunosuppressive microenvironment. IL-32 might be a target molecule for anti-cancer therapy.

Mycosynthesis of selenium nanoparticles using Penicillium tardochrysogenum as a therapeutic agent and their combination with infrared irradiation against Ehrlich carcinoma

Over the past years, the assessment of myco-fabricated selenium nanoparticles (SeNPs) properties, is still in its infancy. Herein, we have highly stable myco-synthesized SeNPs using molecularly identified soil-isolated fungus; Penicillium tardochrysogenum OR059437; (PeSeNPs) were clarified via TEM, EDX, UV–Vis spectrophotometer, FTIR and zeta potential. The therapeutic efficacy profile will be determined, these crystalline PeSeNPs were examined for antioxidant, antimicrobial, MIC, and anticancer potentials, indicating that, PeSeNPs have antioxidant activity of (IC50, 109.11 μg/mL) using DPPH free radical scavenging assay. Also, PeSeNPs possess antimicrobial potential against Penicillium italicum RCMB 001,018 (1) IMI 193,019, Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC 4330 and Porphyromonas gingivalis RCMB 022,001 (1) EMCC 1699; with I.Z. diameters and MIC; 16 ± 0.5 mm and MIC 500 µg/ml, 11.9 ± 0.6 mm, 500 µg/ml and 15.9±0.6 mm, 1000 µg/ml, respectively. Additionally, TEM micrographs were taken for P. italicum treated with PeSeNPs, demonstrating the destruction of hyphal membrane and internal organelles integrity, pores formation, and cell death. PeSeNP alone in vivo and combined with a near-infrared physiotherapy lamp with an energy intensity of 140 mW/cm2 showed a strong therapeutic effect against cancer cells. Thus, PeSeNPs represent anticancer agents and a suitable photothermal option for treating different kinds of cancer cells with lower toxicity and higher efficiency than normal cells. The combination therapy showed a very large and significant reduction in tumor volume, the tumor cells showed large necrosis, shrank, and disappeared. There was also improvement in liver ultrastructure, liver enzymes, and histology, as well as renal function, urea, and creatinine.

Acacetin inhibited non-small-cell lung cancer (NSCLC) cell growth via upregulating miR-34a in vitro and in vivo

Acacetin, one of the flavonoid compounds, is a natural product found in various plants, including Silver birch, and Damiana. Previous studies showed that acacetin has anti-cancer effects on many kinds of cancer cells, however, the role of and the mechanisms of actions of acacetin on non-small cell lung cancer (NSCLC) cells is still not fully understood. Herein, we found that, in vitro, acacetin inhibited the proliferation, invasion, and migration of NSCLC cells, A549 and H460, in a dose-dependent manner. Meanwhile, flow cytometry assay results showed that acacetin induced G2/M phase cell cycle arrest, and apoptosis of NSCLC cells. In vivo, acacetin suppressed tumor formation of A549-xenografted nude mice model with no obvious toxicities. Western blotting results showed that the protein levels of cell cycle-related proteins cyclin B1, cyclin D, and anti-apoptotic protein Bcl-2 had decreased, while the apoptosis-related protein Bak had increased both in NSCLC cells and in A549-xenografted tumor tissues. For investigating the molecular mechanism behind the biological effects of acacetin on NSCLC, we found that acacetin induced the expression levels of tumor suppressor p53 both in vitro and in vivo. MicroRNA, miR-34a, the direct target of p53, has been shown anti-NSCLC proliferation effects by suppressing the expression of its target gene programmed death ligand 1 (PD-L1). We found that acacetin upregulated the expression levels of miR-34a, and downregulated the expression levels of PD-L1 of NSCLC cells in vitro and of tumors in vivo. In vitro, knockdown p53 expression by siRNAs reversed the induction effects of acacetin on miR34a expression and abolished the inhibitory activity of acacetin on NSCLC cell proliferation. Furthermore, using agomir and antagomir to overexpress and suppress the expression miR-34a in NSCLC cells was also examined. We found that miR-34a agomir showed similar effects as acacetin on A549 cells, while miR-34a antagomir could partially or completely reverse acacetin’s effects on A549 cells. In vivo, intratumor injection of miR-34a antagomir could drastically suppress the anti-tumor formation effects of acacetin in A549-xenografted nude mice. Overall, our results showed that acacetin inhibits cell proliferation and induces cell apoptosis of NSCLC cells by regulating miR-34a.

Targeted Cancer Stem Cell Therapeutics: An Update.

Cancer stem cells (CSCs) have become a key player in the growth of tumors, the spread of cancer, and the resistance to therapeutic interventions. Targeting these elusive cell populations has the potential to fundamentally alter cancer treatment plans. CSCs, also known as tumor-initiating cells (TICs), are thought to play a role in both medication resistance and cancer recurrence. This is explained by their capacity to regenerate themselves and change into different kinds of cancer cells. Due to their higher expression of ATP-binding cassette (ABC) membrane transporters, enhanced epithelial to mesenchymal (EMT) characteristics, improved immune evasion, activation of survival signaling pathways, and improved DNA repair mechanisms, CSCs exhibit extraordinary resistance to therapies. This comprehensive analysis delves into advancements in the domain of Targeted Cancer Stem Cell Therapeutics, concentrating on unraveling the distinctive traits of CSCs and the therapeutic methods devised to eliminate them.

CD36: The Bridge between Lipids and Tumors.

It has been found that the development of some cancers can be attributed to obesity, which is associated with the excessive intake of lipids. Cancer cells undergo metabolic reprogramming, shifting from utilizing glucose to fatty acids (FAs) for energy. CD36, a lipid transporter, is highly expressed in certain kinds of cancer cells. High expressions of CD36 in tumor cells triggers FA uptake and lipid accumulation, promoting rapid tumor growth and initiating metastasis. Meanwhile, immune cells in the tumor microenvironment overexpress CD36 and undergo metabolic reprogramming. CD36-mediated FA uptake leads to lipid accumulation and has immunosuppressive effects. This paper reviews the types of FAs associated with cancer, high expressions of CD36 that promote cancer development and progression, effects of CD36 on different immune cells in the tumor microenvironment, and the current status of CD36 as a therapeutic target for the treatment of tumors with high CD36 expression.

Regulating donor configuration to develop AIE-active type I photosensitizers for lipid droplet imaging and high-performance photodynamic therapy under hypoxia.

Type I photodynamic therapy is considered to be a more promising cancer treatment than type II photodynamic therapy due to its non-oxygen-dependent characteristics. In this work, three D-A structure N,N'-dihydrophenazine (DHP)-based photosensitizers DP-CNPY, SMP-CNPY and DMP-CNPY were designed and synthesized by introducing different numbers of methyl groups in the backbone neighbor of DHP as the donor and combined with the typical strong electron acceptor 2-(pyridin-4-yl)acetonitrile. Among the three photosensitizers, SMP-CNPY with one methyl modification showed the best type I ROS (O2-˙, ˙OH) generation capacity and AIE performance. By encapsulation, SMP-CNPY was fabricated into nanoparticles, and SMP-CNPY NPs exhibited lipid droplet targeting ability with near-infrared (NIR) emission. Cell experiments have proved that SMP-CNPY NPs can effectively kill different kinds of cancer cells under normal oxygen conditions. Even under hypoxic and extreme hypoxic conditions, SMP-CNPY NPs can still produce ROS and kill cancer cells. This work holds significant potential in the field of type I AIE-active photosensitizers and provides a new strategy for overcoming the hypoxic dilemma in the malignant tumor microenvironment.

Clusterin is upregulated by erastin, a ferroptosis inducer and exerts cytoprotective effects in pancreatic adenocarcinoma cells.

Ferroptosis is a novel form of cell death, which is distinguished from apoptosis and necrosis, and characterized by accumulation of lipid-based reactive oxygen species (ROS) in an iron-dependent manner. Erastin, a small molecule, was widely reported to trigger ferroptosis in various kinds of cancer cells, including pancreatic cancer cells by inducing ROS accumulation. However, how erastin treatment exerts cytotoxicity is not still fully understood. In this study, the effects of erastin in causing pancreatic cancer cell death via inducing ferroptosis and apoptosis are investigated. As expected, erastin treatment caused ROS accumulation, increase in iron concentration and non-apoptotic cell death, which is different from that of induced by apoptosis inducer, staurosporine. Interestingly, erastin treatment caused the upregulation of clusterin, which contributes to the regulation of malignant behaviors of pancreatic cancer, including preventing apoptosis and inducing chemoresistance. Without erastin treatment, overexpressed clusterin significantly promoted cell proliferation, which is consistent with its cytoprotective roles. After erastin treatment, overexpressed clusterin decreased erastin-induced ROS accumulation and cell death. By measuring iron concentration, reduced glutathione (GSH) and glutathione peroxidase 4 (GPX4), it is revealed that clusterin caused resistance to erastin-induced ferroptosis potentially via maintaining the enzymatic activity of GPX4, without disturbing GSH amount. Thus, ferroptosis inducer, erastin, may crosstalk with apoptotic cell death via regulating clusterin, indicating a more complex regulatory network between ferroptosis and apoptosis.

Highly sensitive Ag/BaTiO3/MoS2 nano composite layer based SPR sensor for detection of blood and cervical cancer

In this article, a nano-composite Ag/BaTiO3/MoS2 multilayer coating-based surface plasmon resonance (SPR) sensor with high sensitivity and figure of merit for the detection of cancer cells is analyzed. The proposed SPR biomedical sensor structure is built on the angular interrogation approach to utilizing the refractive index component, attenuated total reflection (ATR) analysis is employed to identify different kinds of cancer cells. The resonance angle varied as the refractive index (RI) of healthy and cancerous cells changed. Which ranged from 1.368 to 1.392 for increasing concentration in cervical (HeLa cells) and blood (Jurkat cells), RI 1.376 to 1.390 changes as the concentration of cancerous cells increases in healthy cells. The maximum estimated sensitivities for cervical (HeLa) and blood (Jurkat) cancer cells based on numerical data were 271.25 deg/RIU and 290.714 deg/RIU, respectively. The proposed BK7/Ag/BaTiO3/ MoS2has the ability to identify cancerous and healthy cells with the greatest overall sensitivity, as demonstrated by layered structures. Finally, the numerical results analyzed in this manuscript revealed a high degree of sensitivity and FoM compared to those of previous research studies.

Simulation study of reconfigurable surface plasmon resonance refractive index sensor employing bismuth telluride and MXene nanomaterial for cancer cell detection

In this study, a highly angular sensitive surface plasmon resonance (SPR) biosensor has been designed for cancer cell detection. The proposed surface plasmon resonance biosensor structure is based on Kretschmann configuration, which works on an angular interrogation technique. The proposed SPR biosensor has enormous possibility to detect the various kind of cancer cells. The refractive index alteration of different cancerous (skin, cervical and blood) cells is 1.360–1.390. The proposed SPR biosensor is stacked with multilayers having CaF2 prism, silver metal, bismuth telluride (Bi2Te3) and MXene (Ti3C2Tx) layers. The performance parameters like angular sensitivity, quality factor, detection accuracy, and electric field intensity distribution have been optimized in this article. Here, various kind of cancer cells (skin, cervical and blood) have been also analyzed and corresponding angular sensitives are 252.20, 305.70 and 319.46 deg R−1IU−1 respectively. The proposed SPR biosensor shows best results for blood cancer cell detection. Some other important performance parameters like detection accuracy, quality factor, and electric field intensity distribution have also been calculated for proposed SPR biosensor device. The simulation results have been performed by MATLAB 2019a software. The proposed SPR biosensor design may open a new way for the medical industry.

Pachymic Acid Inhibits Growth and Metastatic Potential in Liver Cancer HepG2 and Huh7 Cells.

Pachymic acid (PA), exacted from Polyporaceae, has been known for its biological activities including diuretic, dormitive, anti-oxidant, anti-aging, anti-inflammatory and anticancer properties in several types of diseases. Recently, studies have demonstrated that PA could suppress cell growth and induce cell apoptosis in different kinds of cancer cells. But the underlying mechanisms remain poorly elucidated. In the current study, we investigated the effect of pachymic acid on liver cancer cells and its underlying mechanisms. Our results evidenced that pachymic acid effectively inhibited the cell growth and metastatic potential in HepG2 and Huh7 cells. Mechanistically, we revealed that pachymic acid triggered cell apoptosis by increasing caspase 3 and caspase 9 cleavage, upregulating Bax and cytochrome c expression, while reducing the expression of Bcl2. Besides, pachymic acid could markedly inhibit the cell invasion and migration and cell metastatic potential by mediating epithelial-to-mesenchymal transition (EMT) markers and metastasis-associated genes in HepG2 and Huh7 cells. In addition, we demonstrated that FAK-Src-Jun N-terminal kinase (JNK)-matrix metalloproteinase 2 (MMP2) axis was involved in PA-inhibited liver cell EMT. Together, these results contribute to our deeper understanding of the anti-cancer effects of pachymic acid on liver cancer cells. This study also provided compelling evidence that PA might be a potential therapeutic agent for liver cancer treatment.

Universal nanosonosensitizer for ROS-mediated reduction of various cancer cells.

Sonodynamic therapy (SDT) has attracted great attention due to its deep tissue penetration, uniform tissue energy distribution, and noninvasiveness features. Additionally, external triggers can precisely focus on the tumor site with good specificity and high controllability. In the past decade, numerous sonosensitizers have been designed and used for SDT. However, the research and development of universal sonosensitizers for many different types of tumors are equally important in clinical treatment. Herein, we synthesized and studied the universality of four MWO4-PEG nanoparticles (NPs). All of the four MWO4-PEG NPs exhibited highly efficient ultrasound (US)-triggered production of 1O2 and ˙OH, enabling effective decreased cell viability, increased cell apoptosis rate, and a destruction of mouse tumors under US stimulation. The US-triggered NPs indicated good sonosensitivity and low toxicity to nine kinds of cancer cells. After accomplishing its therapeutic functions, NiWO4-PEG could be metabolized by the mouse body without any long-term toxicity. The PEGylated MWO4-PEG NPs shown in this study would provide efficient and universal US-triggered cancer therapy with the advantages of a cost-effective, convenient, and noninvasive agent that is promising for noninvasive SDT cancer treatment.

Multiple Types of Cancer Classification Using CT/MRI Images Based on Learning Without Forgetting Powered Deep Learning Models

Cancer is the second biggest cause of death worldwide, accounting for one of every six deaths. On the other hand, early detection of the disease significantly improves the chances of survival. The use of Artificial Intelligence (AI) to automate cancer detection might allow us to evaluate more cases in less time. In this research, AI-based deep learning models are proposed to classify the images of eight kinds of cancer, such as lung, brain, breast, and cervical cancer. This work evaluates the deep learning models, namely Convolutional Neural Networks (CNN), against classifying images with cancer traits. Pre-trained CNN variants such as MobileNet, VGGNet, and DenseNet are employed to transfer the knowledge they learned with the ImageNet dataset to detect different kinds of cancer cells. We use Bayesian Optimization to find the suitable values for the hyperparameters. However, transfer learning could make it so that models can no longer classify the datasets they were initially trained. So, we use Learning without Forgetting (LwF), which trains the network using only new task data while keeping the network’s original abilities. The results of the experiments show that the proposed models based on transfer learning are more accurate than the current state-of-the-art techniques. We also show that LwF can better classify both new datasets and datasets that have been trained before.

Deep transfer learning for IDC breast cancer detection using fast AI technique and Sqeezenet architecture.

One of the most effective approaches for identifying breast cancer is histology, which is the meticulous inspection of tissues under a microscope. The kind of cancer cells, or whether they are cancerous (malignant) or non-cancerous, is typically determined by the type of tissue that is analyzed by the test performed by the technician (benign). The goal of this study was to automate IDC classification within breast cancer histology samples using a transfer learning technique. To improve our outcomes, we combined a Gradient Color Activation Mapping (Grad CAM) and image coloring mechanism with a discriminative fine-tuning methodology employing a one-cycle strategy using FastAI techniques. There have been lots of research studies related to deep transfer learning which use the same mechanism, but this report uses a transfer learning mechanism based on lightweight Squeeze Net architecture, a variant of CNN (Convolution neural network). This strategy demonstrates that fine-tuning on Squeeze Net makes it possible to achieve satisfactory results when transitioning generic features from natural images to medical images.

Dry Grinding Synthesis and Docking Study of Cyclopentanone-Sulfur Containing Compounds with Anti-Proliferative Activity for HepG-2 and A-549 Cancer Cell Lines.

The dry grinding method is a green technique for efficient organic synthesis with numerous advantages, such as mild reaction conditions, environmental acceptability, simple segregation, and refinement, as well as elevated selectivity and efficiency. The aim of the present work is to design and synthesize cyclopentylidene-hydrazino)- thiazole derivatives using dry grinding conditions to investigate their antitumor activity against two cell lines, namely, HepG-2 and A-549. In this context, we synthesized a series of thiazole incorporated cyclopentane through hydrazone- group and 2-cyclopentylidenehydrazine-1-carbimidic-2-ethoxy-N-aryl-2-oxoacetohydrazonic thioanhydride under dry grinding within minutes and excellent to good yield. All spectral data confirmed the proposed structures. In addition to antitumor activity investigations against the two kinds of cancer cells, molecular docking studies were conducted using Macrophage Migration Inhibitory Factor (Pdb: 4k9g) and Lysozyme C (Pdb: 2f4a), the overexpressed proteins in the human liver cancer cell (HepG-2) and lung cancer cell lines (A-549), respectively. Two derivatives, 9b, and 9d, showed the highest antitumor activity against the two cell lines HepG-2 and A-549. Also, docking results revealed a high energy score ranging from -7.1590 to -5.9364 Kcal/mol with Macrophage Migration Inhibitory Factor (Pdb: 4k9g), more than that the energy score = -4.118 Kcal/mol of co-crystallized ligand. Moreover, the tested derivatives showed energy score varies from -6.0802 to -4.5503 Kcal/mol against Lysozyme C (Pdb: 2f4a).

A dual-biomarker-controlled DNA logic platform assisted with multivariate statistical analysis for accurate and high-throughput recognition of cancer cells

Present DNA logic platforms mainly focused on distinguishing a specific kind of cancer cell from several other types of cell lines, while limited efforts have been paid to high-throughput recognition of cancer cells. A new DNA logic platform coupled with multivariate statistical analysis was developed to classify seven kinds of cancer cells. Four confined DNA circuits containing localized catalytic hairpin assembly (LCHA) and apurinic/apyrimidinic endonuclease 1 (APE1)-assisted circuits were conjugated to a protein of streptavidin (SA) for DNA logic platform. The mismatch minimizes the circuit leakage of the confined DNA circuits by inhibiting the incorrectly intramolecular structure switch. Benefitting from the spatial-confined effect, the DNA logic platform as a modified AND logic gate sensitively responded to the dual intracellular biomarkers, thereby generating strong dual fluorescent output signals in living cells. Based on the fluorescent cell imaging, multidimensional data collected from 50 individual cells were concatenated as a dataset for multivariate statistical analysis. Principal component analysis (PCA) shows distinct clustering among the seven kinds of cancer cell lines. A random forest algorithm obtained the specificity and sensitivity of 100%. Therefore, the DNA logic platform coupling with multivariate statistical analysis shows promising potential for cancer diagnosis and treatment.

Dually stimulative single-chain polymeric nano lock with dynamic ligands for sensitive detection of circulating tumor cells

Circulating tumor cells (CTCs) are important markers for cancer diagnosis and monitoring. However, CTCs detection remains challenging due to their scarcity, where most of the detection methods are compromised by the loss of CTCs in pre-enrichment, and by the lack of universal antibodies for capturing different kinds of cancer cells. Herein, we report a single-chain based nano lock (SCNL) polymer incorporating dually stimulative dynamic ligands that can bind with a broad spectrum of cancer cells and CTCs overexpressing sialic acid (SA) with high sensitivity and selectivity. The high sensitivity is realized by the polymeric single chain structure and the multi-valent functional moieties, which improve the accessibility and binding stability between the target cells and the SCNL. The highly selective targeting of cancer cells is achieved by the dynamic and dually stimulative nano lock structures, which can be unlocked and functionalized upon simultaneous exposure to overexpressed SA and acidic microenvironment. We applied the SCNL to detecting cancer cells and CTCs in clinical samples, where the detection threshold of SCNL reached 4 cells/mL. Besides CTCs enumeration, the SCNL approach could also be extended to metastasis assessment through monitoring the expressing level of surface SA on cancer cells.

Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents.

With the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicated that majority of new compounds exhibited improved antitumor activity compared with the parent compound betulonic acid. Compound BoA2C, in particular, had the most significant action with IC50 value of 3.39 μM against MCF-7 cells, while it showed lower cytotoxicity on MDCK cell line than cisplatin. Furthermore, we discovered that BoA2C strongly increased MCF-7 cell damage mostly by influencing arginine and fatty acid metabolism. In addition, the structure-activity relationships were briefly discussed. The results of this study suggested that the introduction of different diazines at C-28 could selectively inhibit different kinds of cancer cells and might be an effective way to synthesize potent anticancer lead compound from betulonic acid.