Kill HeLa Cells Research Articles

Synergistic cytotoxicity of olive leaf extract-loaded lipid nanocarriers combined with Newcastle disease virus against cervical cancer cells.

Despite recent medical progress, cervical cancer remains a major global health concern for women. Current standard treatments have limitations such as non-specific toxicity that necessitate development of safer and more effective therapeutic strategies. This research evaluated the combinatorial effects of olive leaf extract (OLE), rich in anti-cancer polyphenols, and the oncolytic Newcastle disease virus (NDV) against human cervical cancer cells. OLE was efficiently encapsulated (>94% loading) within MF59 lipid nanoparticles and nanostructured lipid carriers (NLCs; contains Precirol as NLC-P, contains Lecithin as NLC-L) to enhance stability, bioavailability, and targeted delivery. Physicochemical analysis confirmed successful encapsulation of OLE within nanoparticles smaller than 150 nm. In vitro cytotoxicity assays demonstrated significantly higher toxicity of the OLE-loaded nanoparticle formulations on HeLa cancer cells versus HDF normal cells (P<0.05). MF59 achieved the highest encapsulation efficiency, while NLC-P had the best drug release profile. NDV selectively infected and killed HeLa cells versus HDF cells. Notably, combining NDV with OLE-loaded nanoparticles led to significantly enhanced synergistic cytotoxicity against cancer cells (P<0.05), with NLC-P (OLE) and NDV producing the strongest effects. Apoptosis and cell cycle analyses confirmed the increased anti-cancer activity of the combinatorial treatment, which induced cell cycle arrest. This study provides evidence that co-delivery of OLE-loaded lipid nanoparticles and NDV potentiates anti-cancer activity against cervical cancer cells in vitro through a synergistic mechanism, warranting further development as a promising alternative cervical cancer therapy.

Novel naphthalimide bridged zinc porphyrin/BODIPY nanomaterials with D-A structure for photodynamic therapy

As a non-invasive cancer therapy method, photodynamic therapy (PDT) shows tremendous promise in clinical cancer treatment. Light-activated singlet oxygen production of photosensitizers (PSs) is the prerequisite for cancer PDT, and the use of organic photosensitizers is always limited by visible light-based activation, hydrophilicity, biocompatibility, selectivity and quantum yield of singlet oxygen. Currently, both zinc porphyrin- and BODIPY-based structures have been widely used in the development of PDT PSs. Here, we developed a novel naphthalimide bridged zinc porphyrin/BODIPY molecule (Por-BDP-1) with two poly(ethylene glycol) (PEG) chains, in which D-A structure was constructed between the naphthalimide group and porphyrin group. After self-assembly into nanoparticles, Por-BDP-1 NPs (Diameter: 122.4 nm) could quench fluorescence in 600–700 nm, bind with calf thymus-DNA, and produce singlet oxygen during light-irradiation (laser: 680 nm, 1.0 W/cm[Formula: see text]. In addition, Por-BDP-1 NPs effectively killed HeLa cells with a IC[Formula: see text] value = 44.8 μg/mL and showed a lower dark toxicity under the same conditions. All our results demonstrated that our naphthalimide bridged zinc porphyrin/BODIPY nano-photosensitizer is a promising nanoagent for PDT in the clinic.

Small-Molecule Endoplasmic Reticulum Stress Inducer Triggers Apoptosis in Cancer Cells.

Endoplasmic reticulum (ER) is highly critical for the sub-cellular protein synthesis, post-translational modifications and myriads of signalling pathways to maintain cellular homeostasis. Consequently, dysregulation in the ER functions leads to the ER stress in different pathological situations including cancer. Hence, exploring small molecules to induce ER stress emerged as one of the unorthodox strategies for future cancer therapeutics. However, development of ER targeted novel small molecules remains elusive due to the dearth of ER targeting moieties. Herein we have synthesized a small library of 3-methoxy-pyrrole-enamine through a concise strategy. Screening of this library in cervical (HeLa), colon (HCT-116), breast (MCF7) and lung cancer (A549) cells identified a novel small molecule which localized into the ER of the HeLa cervical cancer cells within 3 h, induced ER stress through the increased expression of ER stress markers (CHOP, IRE1α, PERK, BiP and Cas-12) and triggered the programmed cell death (apoptosis) leading to remarkable HeLa cell killing. This novel small molecule can be explored further as a tool to understand the chemical biology of ER towards the development of ER targeted cancer therapeutics.

Novel Gold Nanorods@Thiolated Pectin on the Killing of HeLa Cells by Photothermal Ablation.

Gold nanorods (AuNRs) have attracted attention in the field of biomedicine, particularly for their potential as photothermal agents capable of killing tumor cells by photothermic ablation. In this study, the synthesis of novel AuNRs stabilized with thiolated pectin (AuNR@SH-PEC) is reported. To achieve this, thiolated pectin (SH-PEC) was obtained by chemically binding cysteamine motifs to the pectin backbone. The success of the reaction was ascertained using FTIR-ATR. Subsequently, the SH-PEC was used to coat and stabilize the surface of AuNRs (AuNR@SH-PEC). In this context, different concentrations of SH-PEC (0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mg/mL) were added to 0.50 mL of AuNRs suspended in CTAB, aiming to determine the experimental conditions under which AuNR@SH-PEC maintains stability. The results show that SH-PEC effectively replaced the CTAB adsorbed on the surface of AuNRs, enhancing the stability of AuNRs without affecting their optical properties. Additionally, scanning electron and atomic force microscopy confirmed that SH-PEC is adsorbed into the surface of the AuNRs. Importantly, the dimension size (60 × 15 nm) and the aspect ratio (4:1) remained consistent with those of AuNRs stabilized with CTAB. Then, the photothermal properties of gold nanorods were evaluated by irradiating the aqueous suspension of AuNR@SH-PEC with a CW laser (808 nm, 1 W). These results showed that photothermal conversion efficiency is similar to the photothermal conversion observed for AuNR-CTAB. Lastly, the cell viability assays confirmed that the SH-PEC coating enhanced the biocompatibility of AuNR@SH-PEC. Most important, the viability cell assays subjected to laser irradiation in the presence of AuNR@SH-PEC showed a decrease in the cell viability relative to the non-irradiated cells. These results suggest that AuNRs stabilized with thiolated pectin can potentially be exploited in the implementation of photothermal therapy.

Is Proteolytic Cleavage Essential for the Enhanced Activity of Hydra Pore-Forming Toxin, HALT-4?

Hydra actinoporin-like toxin 4 (HALT-4) differs from other actinoporins due to its N-terminal propart that contains approximately 103 additional residues. Within this region, we identified five dibasic residues and assumed that, when cleaved, they could potentially exhibit HALT-4's cytolytic activity. We created five truncated versions of HALT-4 (tKK1, tKK2, tRK3, tKK4 and tKK5) to investigate the role of the N-terminal region and potential cleavage sites on the cytolytic activity of HALT-4. However, our results demonstrated that the propart-containing HALT-4 (proHALT-4), as well as the truncated versions tKK1 and tKK2, exhibited similar cytolytic activity against HeLa cells. In contrast, tRK3, tKK4 and tKK5 failed to kill HeLa cells, indicating that cleavage at the KK1 or KK2 sites did not enhance cytolytic activity but may instead facilitate the sorting of tKK1 and tKK2 to the regulated secretory pathway for eventual deposition in nematocysts. Moreover, RK3, KK4 and KK5 were unlikely to serve as proteolytic cleavage sites, as the amino acids between KK2 and RK3 are also crucial for pore formation.

6-Shogaol as a Novel Thioredoxin Reductase Inhibitor Induces Oxidative-Stress-Mediated Apoptosis in HeLa Cells

Inhibition of thioredoxin reductase (TrxR) is a crucial strategy for the discovery of antineoplastic drugs. 6-Shogaol (6-S), a primary bioactive compound in ginger, has high anticancer activity. However, its potential mechanism of action has not been thoroughly investigated. In this study, we demonstrated for the first time that 6-S, a novel TrxR inhibitor, promoted oxidative-stress-mediated apoptosis in HeLa cells. The other two constituents of ginger, 6-gingerol (6-G) and 6-dehydrogingerduone (6-DG), have a similar structure to 6-S but fail to kill HeLa cells at low concentrations. 6-Shogaol specifically inhibits purified TrxR1 activity by targeting selenocysteine residues. It also induced apoptosis and was more cytotoxic to HeLa cells than normal cells. The molecular mechanism of 6-S-mediated apoptosis involves TrxR inhibition, followed by an outburst of reactive oxygen species (ROS) production. Furthermore, TrxR knockdown enhanced the cytotoxic sensitivity of 6-S cells, highlighting the physiological significance of targeting TrxR by 6-S. Our findings show that targeting TrxR by 6-S reveals a new mechanism underlying the biological activity of 6-S and provides meaningful insights into its action in cancer therapeutics.

Dog-bone shaped gold nanoparticle-mediated chemo-photothermal therapy impairs the powerhouse to trigger apoptosis in cancer cells.

The mitochondrion has emerged as one of the uncommon targets in cancer therapeutics due to its involvement in cancer generation and progression. Consequently, nanoplatform mediated delivery of anti-cancer drugs into the mitochondria of cancer tissues demonstrated immense potential in cancer treatment. In the last couple of decades, gold nanoparticles have gained incredible attention in biomedical applications due to their easy synthesis, size-shape tenability, optical properties and outstanding photothermal ability. However, application of gold nanoparticles to target mitochondria to induce the chemo-photothermal effect in cancer has remained in its infancy. To address this, herein we have engineered dog-bone shaped gold nanoparticles (Mito-AuDB-NPs) comprising cisplatin and 10-hydroxycamptothecin as chemotherapeutic drugs along with the triphenylphosphonium (TPP) cation for mitochondria homing. Mito-AuDB-NPs exhibited a remarkable increase in temperature till 56 °C upon 18 min irradiation with 740 nm NIR LED light with a power density of 0.9 W cm-2. These Mito-AuDB-NPs successfully homed into the mitochondria of HeLa cervical cancer cells within 1 h and induced mitochondrial outer membrane permeabilization (MOMP) under the chemo-photothermal effect leading to the generation of reactive oxygen species (ROS). This Mito-AuDB-NP-mediated mitochondrial damage triggered programmed cell death (apoptosis) by decreasing the expression of anti-apoptotic Bcl-2/Bcl-xl and increasing the expression of pro-apoptotic BAX followed by caspase-3 cleavage towards extraordinary HeLa cell killing in a synergistic manner without showing toxicity towards non-cancerous RPE-1 human epithelial retinal pigment cells. We anticipate that this dog-bone shaped gold nanoparticle-mediated chemo-photothermal impairment of mitochondria in the cancer cells can open a new direction towards organelle targeted cancer therapy.

Olfactory receptor OR5V1 is an effective target for CAR T cells in ovarian cancer (207)

Olfactory receptor OR5V1 is an effective target for CAR T cells in ovarian cancer (207)

The Effect of 5-Aminolevulinic Acid Photodynamic Therapy in Promoting Pyroptosis of HPV-Infected Cells

5-aminolevulinic acid photodynamic therapy (ALA-PDT) is highly effective in the treatment of condyloma acuminata (CA). Previous research has indicated that ALA-PDT could induce cell death by different mechanisms, including apoptosis and autophagy, but the role of pyroptosis in ALA-PDT remains uncertain. Thus, this study aimed to explore whether pyroptosis is a potential mechanism of ALA-PDT killing human papillomavirus (HPV) infected cells. HPV-positive HeLa cells were exposed to ALA-PDT, then cell viability assay, lactate dehydrogenase release (LDH) assay, detection of reactive oxygen species (ROS), quantitative real-time PCR (qPCR), and western blot were used to evaluate pyroptosis induced by ALA-PDT. Results suggested that ALA-PDT enhanced the expression of NLRP3, caspase-1, GSDMD, and the production of inflammatory cytokines such as IL-1β and IL-18. In addition, ALA-PDT induced the production of ROS and led to the destruction of the cell membrane. The inhibition of pyroptosis reduced the killing of HeLa cells by ALA-PDT. This study demonstrates that ALA-PDT induces pyroptosis in HPV-positive cells, which provides some explanation for the mechanism of ALA-PDT to treat CA and HPV infection-related diseases.

Multifunctional MoS2 composite nanomaterials for drug delivery and synergistic photothermal therapy in cancer treatment

Due to its excellent photothermal performance, MoS2 is more and more widely used in cancer treatment. In this study, a novel MoS2 composite nanosheets material with lamellar structure and good water solubility (BBPL-MoS2-LP) was synthesized, which had high photothermal conversion efficiency and good biocompatibility. The drug loading efficiency of doxorubicin (DOX) on the composite nanosheets reached 34.43%. Compared with the drug release rate of 15% at pH 7.0, the release degree of DOX was higher at a slightly acidic environment of pH 5.5, reaching 30%. Under the irradiation of near infrared laser (NIR), the drug release was significantly enhanced, indicating that the composite material can be used as a dual response system. The release of DOX would be controlled by pH and near infrared laser (NIR) irradiation. It was also found that BBPL-MoS2-LP could effectively penetrate cell membrane under the endocytosis mechanism mediated by biotin receptor and release drugs in HeLa cells. Cytotoxicity and apoptosis experiments showed that BBPL-MoS2-LP had better ability to kill HeLa cells than single drug or photothermal irradiation alone. The as-prepared multifunctional composite nanosheets in this study has great potential in effective drug delivery and photothermal chemotherapy for tumor treatment.

Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for NO-Photothermal Synergistic Cancer Therapy.

Cancer is still one of the major health issues faced by human beings today. Various nanomaterials have been designed to treat tumors and have made great progress. Herein, we used amino-functionalized metal organic framework (UiO-66-NH2) as superior templates and successfully synthesized the UiO-66-NH2@Aushell composite nanoparticles (UA) with high loading capacity and excellent photothermal properties through a simple and gentle method. In addition, due to the rich pore structure and excellent biocompatibility of the as-prepared composite nanoparticles, the hydrophobic NO donor BNN6 (N,N′-Di-sec-butyl-N,N′-dinitroso-1, 4-phenylenediamine) molecule was efficiently delivered. Based on the phenomenon where BNN6 molecules can decompose and release NO at high temperature, when UiO-66-NH2@Aushell-BNN6 composite nanoparticles (UA-BNN6) entered tumor cells and were irradiated by NIR, the porous gold nanoshells on the surface of composite nanoparticles induced an increase in temperature through the photothermal conversion process and promoted the decomposition of BNN6 molecules, releasing high concentration of NO, thus efficiently killing HeLa cells through the synergistic effect of NO-photothermal therapy. This effective, precise and safe treatment strategy controlled by NIR laser irradiation represents a promising alternative in the field of cancer treatment.

Folic acid functionalized aggregation-induced emission nanoparticles for tumor cell targeted imaging and photodynamic therapy.

Recently, molecules with aggregation-induced luminescence (AIE) characteristics have received more and more attention due to the fluorescence of traditional dyes being easily quenched in the aggregated state. AIE molecules have significant advantages, such as excellent light stability, bright fluorescence, high contrast, and large Stokes shift. These characteristics have aroused wide interest of researchers and opened up new applications in many fields, especially in the field of biological applications. However, AIE molecules or their aggregates have certain limitations in multifunctional biological research due to their low specific targeting ability, poor biocompatibility, and poor stability in physiological body fluids. In order to overcome these problems, a novel nanoparticle, FFM1, was fabricated and characterized. FFM1 displayed good water solubility, biocompatibility, and AIE emission properties. It could target HeLa cells specifically by recognizing their folate receptor. Reactive oxygen triggered by light irradiation induced tumor cell apoptosis. Summarily, FFM1 displayed excellent capacity in target imaging and photodynamic killing of HeLa cells. It has shown potential application value in targeted diagnosis and photodynamic therapy of tumors, and has important guiding significance for the treatment of malignant tumors. It paves a way for the development of a novel strategy for tumor theranostics.

Lockdown of mitochondrial Ca2+ extrusion and subsequent resveratrol treatment kill HeLa cells by Ca2+ overload.

Anticancer effect of resveratrol and the role of sodium/lithium/calcium exchanger in context with calcium ions are studied in human cervical cancer cell line. This therapeutic approach using siNCLX mediated gene silencing and drug therapy with resveratrol indicates the disruption of calcium homeostasis, increase in caspase (-3, 8, 9) mRNA expressions and DNA damage leading to apoptotic cell death. Monitoring the intracellular Ca2+ changes using fluo-4AM indicates highest rise in [Ca2+] level in sodium/lithium/calcium exchanger silenced group with five different stages, that is distinguishable based on the fluorescence intensity. In resveratrol treated and siNCLX + resveratrol treated groups no such cell staging differences were observed, despite uniform Ca2+ rise followed by decrease in the intensity. Integrating RNAi gene silencing of sodium/lithium/calcium exchanger with resveratrol can form the most interesting, efficient and promising therapeutic strategy in the treatment of cancer.

Selective Inhibition of DNA Polymerase β by a Covalent Inhibitor.

DNA polymerase β (Pol β) plays a vital role in DNA repair and has been closely linked to cancer. Selective inhibitors of this enzyme are lacking. Inspired by DNA lesions produced by antitumor agents that inactivate Pol β, we have undertaken the development of covalent small-molecule inhibitors of this enzyme. Using a two-stage process involving chemically synthesized libraries, we identified a potent irreversible inhibitor (14) of Pol β (KI = 1.8 ± 0.45 μM, kinact = (7.0 ± 1.0) × 10-3 s-1). Inhibitor 14 selectively inactivates Pol β over other DNA polymerases. LC-MS/MS analysis of trypsin digests of Pol β treated with 14 identified two lysines within the polymerase binding site that are covalently modified, one of which was previously determined to play a role in DNA binding. Fluorescence anisotropy experiments show that pretreatment of Pol β with 14 prevents DNA binding. Experiments using a pro-inhibitor (pro-14) in wild type mouse embryonic fibroblasts (MEFs) indicate that the inhibitor (5 μM) is itself not cytotoxic but works synergistically with the DNA alkylating agent, methylmethanesulfonate (MMS), to kill cells. Moreover, experiments in Pol β null MEFs indicate that pro-14 is selective for the target enzyme. Finally, pro-14 also works synergistically with MMS and bleomycin to kill HeLa cells. The results suggest that pro-14 is a potentially useful tool in studies of the role of Pol β in disease.

Enhancing near-infrared AIE of photosensitizer with twisted intramolecular charge transfer characteristics via rotor effect for AIE imaging-guided photodynamic ablation of cancer cells

Near-infrared (NIR) aggregation-induced emission (AIE) of previous organic photosensitizers is usually weak because of the competition between twisted intramolecular charge transfer (TICT) effect and AIE. Herein, we report a rational molecular design strategy to boost NIR AIE of photosensitizers and still to keep strong 1O2 production capacity via rotor effect. To this end, one new triphenylamine (TPA)-based AIE photosensitizer, TPAM-1, is designed to give strong ability to generate 1O2 but weak NIR fluorescence in the aggregate state due to the strong TICT effect. Another new TPA-based AIE photosensitizer, TPAM-2, is designed by introducing three p-methoxyphenyl units as rotors into the structure of TPAM-1 to modulate the competition between AIE and TICT. TPAM-1 and TPAM-2 exhibit stronger ability to generate 1O2 in the aggregate state than the commercial photosensitizer, Ce6. Furthermore, TPAM-2 gives much brighter NIR luminescence (25-times higher quantum yield) than TPAM-1 in the aggregate state due to the rotor effect. TPAM-2 with strong NIR AIE and 1O2 production capability was encapsulated by DSPE-PEG2000 to give good biocompatibility. The DSPE-PEG2000-encapsulated TPAM-2 nanoparticles show good cell imaging performance and remarkable photosensitive activity for killing HeLa cells. This work provides a new way for designing ideal photosensitizers for AIE imaging-guided photodynamic therapy.

Multimodal image-guided folic acid targeted Ag-based quantum dots for the combination of selective methotrexate delivery and photothermal therapy

Multifunctional quantum dots (QDs) with photothermal therapy (PTT) potential loaded with an anticancer drug and labelled with a targeting agent can be highly effective nano-agents for tumour specific, image-guided PTT/chemo combination therapy of cancer. Ag-chalcogenides are promising QDs with good biocompatibility. Ag2S QDs are popular theranostic agents for imaging in near-infrared with PTT potential. However, theranostic applications of AgInS2 QDs emitting in the visible region and its PTT potential need to be explored. Here, we first present a simple synthesis of small, glutathione (GSH) coated AgInS2 QDs with peak emission at 634 nm, 21% quantum yield, and excellent long-term stability without an inorganic shell. Ag2S-GSH QDs emitting in the near-infrared region (peak emission = 822 nm) were also produced. Both QDs were tagged with folic acid (FA) and conjugated with methotrexate (MTX). About 3-fold higher internalization of FA-tagged QDs by folate-receptor (FR) overexpressing HeLa cells than HT29 and A549 cells was observed. Delivery of MTX by QD-FA-MTX reduced the IC50 of the drug from 10 μg/mL to 2.5–5 μg/mL. MTX release was triggered at acidic pH, which was further enhanced with local temperature increase created by laser irradiation. Irradiation of AgInS2-GSH QDs at 640 nm (300 mW) for 10 min, caused about 10 °C temperature increase but did not cause any thermal ablation of cells. On the other hand, Ag2S-GSH-FA based PTT effectively and selectively killed HeLa cells with 10 min 808 nm laser irradiation via mostly necrosis with an IC50 of 5 μg Ag/mL. Under the same conditions, IC50 of MTX was reduced to 0.21 μg/mL if Ag2S-GSH-FA.

Prevalence and Characterization of Some Colibactin Genes in Clinical Enterobacteriaceae isolates from Iraqi Patients

The members of the family of Eentrobacteriaceae harbour a gene cluster called polyketide synthase (pks) island. This cluster is responsible for the synthesis of the genotoxin colibactin that might have an important role in the induction of double-strand DNA breaks, leading to promote human colorectal cancer (CRC). Eleven out of the eighty eight isolates (12.5%) were pks+, distributed as 7 (8%) isolates of E. coli, 2 (2.25%) of K. pneumoniae and 2 (2.25%) of E. aerogenes. The cytotoxic effects of selected pks+ isolates (E. coli and E. aerogenes) on HeLa cells were represented by decreasing cell numbers and enlarged cell nuclei in comparison to the untreated cells. Cytological changes were observed when the infected HeLa cells cultures were stained with AO/EBr and visualized under fluorescent microscope. Some changes that happened in the color of the nuclear chromatin were accompanied by DNA condensation and degradation and fragmentation of nuclei. HeLa cells with green unchanged nuclear chromatin were alive while those with orange-dark and bright red nuclei were dead. It was concluded that a proportion of the Entreobacteriaceae isolates from Iraqi patients was pks+, which exerted cytotoxic effects upon using them to kill HeLa cells. In this study the microscopic observation of the cell morphology reveals the cellular response to the genotoxic insult, with reduced numbers, striking giant cells phenotype (megalocytosis) and fragmentation of nuclei due to the cell cycle arrest and cellular senescence

Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells.

Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.

A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy.

Nanomedicine has stepped into the spotlight of radiation therapy over the last two decades. Nanoparticles (NPs), especially metallic NPs, can potentiate radiotherapy by specific accumulation into tumors, thus enhancing the efficacy while alleviating the toxicity of radiotherapy. Water radiolysis is a simple, fast and environmentally-friendly method to prepare highly controllable metallic nanoparticles in large scale. In this study, we used this method to prepare biocompatible PEGylated (with Poly(Ethylene Glycol) diamine) platinum nanoflowers (Pt NFs). These nanoagents provide unique surface chemistry, which allows functionalization with various molecules such as fluorescent markers, drugs or radionuclides. The Pt NFs were produced with a controlled aggregation of small Pt subunits through a combination of grafted polymers and radiation-induced polymer cross-linking. Confocal microscopy and fluorescence lifetime imaging microscopy revealed that Pt NFs were localized in the cytoplasm of cervical cancer cells (HeLa) but not in the nucleus. Clonogenic assays revealed that Pt NFs amplify the gamma rays induced killing of HeLa cells with a sensitizing enhancement ratio (SER) of 23%, thus making them promising candidates for future cancer radiation therapy. Furthermore, the efficiency of Pt NFs to induce nanoscopic biomolecular damage by interacting with gamma rays, was evaluated using plasmids as molecular probe. These findings show that the Pt NFs are efficient nano-radio-enhancers. Finally, these NFs could be used to improve not only the performances of radiation therapy treatments but also drug delivery and/or diagnosis when functionalized with various molecules.

Ultrasonic atomizer driven development of doxorubicin-chitosan nanoparticles as anticancer therapeutics: Evaluation of anionic cross-linkers

Doxorubicin is the most common, FDA approved anticancer drug used for cancer therapy, which produces several undesirable side effects to healthy cells. Controlled and targeted therapy is presently gaining significant attention to counter the adverse effects of drugs. This research aims to develop doxorubicin (DOX) loaded chitosan nanoparticles through the ultrasonic atomizer, focusing on the use of two different cross-linkers i.e., poly (sodium 4-styrene sulfonate) and sodium tripolyphosphate (TPP) forming Ch-PSS-DOX and Ch-TPP-DOX nanoparticles respectively. The formulation showed an average size of 80 ± 30 nm for Ch-PSS-DOX and 120 ± 50 nm for Ch-TPP-DOX Nps showed~34% and ~44% drug entrapment efficiency in Ch-PSS-DOX and Ch-TPP-DOX Nps respectively. In-vitro drug release studies showed a controlled and pH-dependent release of DOX throughout 168 h. The cytocompatibility of both the formulation was checked using MTT assay on HeLa and HEK-293 cells, show the preferential killing of HeLa cells as compare to HEK-293 cells, cellular uptake of nanoparticles was confirmed by confocal laser scanning microscopy. The results clearly indicate that the synthesis of chitosan nanoparticles using ultrasonic nanoparticles with different crosslinkers significantly affects the properties of nanoparticles in every way comparing from their size to their in-vitro drug uptake and release.