scholarly journals Enhanced siRNA Delivery and Selective Apoptosis Induction in H1299 Cancer Cells by Layer-by-Layer-Assembled Se Nanocomplexes: Toward More Efficient Cancer Therapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Maryam Sharifiaghdam ◽  
Elnaz Shaabani ◽  
Zeynab Sharifiaghdam ◽  
Herlinde De Keersmaecker ◽  
Riet De Rycke ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Colloidal Stability ◽  
Synergistic Effects ◽  
Drug Carriers ◽  
Core Material ◽  
Layer By Layer ◽  
Solid Core ◽  
Apoptosis Induction ◽  
Electrostatic Assembly

Nanotechnology has made an important contribution to oncology in recent years, especially for drug delivery. While many different nano-delivery systems have been suggested for cancer therapy, selenium nanoparticles (SeNPs) are particularly promising anticancer drug carriers as their core material offers interesting synergistic effects to cancer cells. Se compounds can exert cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis, eventually leading to apoptosis induction in many kinds of cancer cells. Herein, we report on the design and synthesis of novel layer-by-layer Se-based nanocomplexes (LBL-Se-NCs) as carriers of small interfering RNA (siRNA) for combined gene silencing and apoptosis induction in cancer cells. The LBL-Se-NCs were prepared using a straightforward electrostatic assembly of siRNA and chitosan (CS) on the solid core of the SeNP. In this study, we started by investigating the colloidal stability and protection of the complexed siRNA. The results show that CS not only functioned as an anchoring layer for siRNA, but also provided colloidal stability for at least 20 days in different media when CS was applied as a third layer. The release study revealed that siRNA remained better associated with LBL-Se-NCs, with only a release of 35% after 7 days, as compared to CS-NCs with a siRNA release of 100% after 48 h, making the LBL nanocarrier an excellent candidate as an off-the-shelf formulation. When applied to H1299 cells, it was found that they can selectively induce around 32% apoptosis, while significantly less apoptosis (5.6%) was induced in NIH/3T3 normal cells. At the same time, they were capable of efficiently inducing siRNA downregulation (35%) without loss of activity 7 days post-synthesis. We conclude that LBL-Se-NCs are promising siRNA carriers with enhanced stability and with a dual mode of action against cancer cells.

Hyaluronan based Multifunctional Nano-carriers for Combination Cancer Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Menghan Gao ◽  
Hong Deng ◽  
Weiqi Zhang
Keyword(s):  
Cancer Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Drug Carriers ◽  
Functional Sites ◽  
Therapeutic Modalities ◽  
Combination Cancer Therapy ◽  
Targeting Strategy

: Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility, biodegradability, and low immunogenicity, making it one of the most attractive biopolymers used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered to construct different drug-loading nanoparticles (NPs) for CD44- targeted anti-tumor therapy. When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained, which features as a highly effective and self-targeting strategy to combat the cancers with CD44 overexpression. The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many types of HA-based multidrug nano-carriers constructed by different formulation strategies including drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier takes the full advantages of HA as NP matrix, drug carriers and targeting ligand, representing a simplified and biocompatible platform to realize the targeted and synergistic combination therapy against the cancers. In this review, recent progresses about HA-based multidrug nano-carriers for combination cancer therapy are summarized and its potential challenges for translational applications have been discussed.

scholarly journals Hyaluronic Acid-Coated Nanomedicine for Targeted Cancer Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 301 ◽  
Author(s):  
Kim ◽  
Choi ◽  
Choi ◽  
Park ◽  
Ryu
Keyword(s):  
Hyaluronic Acid ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Photothermal Therapy ◽  
Colloidal Stability ◽  
Inorganic Nanoparticles ◽  
Cancer Targeting ◽  
Anionic Polymer ◽  
Enhanced Permeability And Retention ◽  
Interaction With Receptors

Hyaluronic acid (HA) has been widely investigated in cancer therapy due to its excellent characteristics. HA, which is a linear anionic polymer, has biocompatibility, biodegradability, non-immunogenicity, non-inflammatory, and non-toxicity properties. Various HA nanomedicines (i.e., micelles, nanogels, and nanoparticles) can be prepared easily using assembly and modification of its functional groups such as carboxy, hydroxy and N-acetyl groups. Nanometer-sized HA nanomedicines can selectively deliver drugs or other molecules into tumor sites via their enhanced permeability and retention (EPR) effect. In addition, HA can interact with overexpressed receptors in cancer cells such as cluster determinant 44 (CD44) and receptor for HA-mediated motility (RHAMM) and be degraded by a family of enzymes called hyaluronidase (HAdase) to release drugs or molecules. By interaction with receptors or degradation by enzymes inside cancer cells, HA nanomedicines allow enhanced targeting cancer therapy. In this article, recent studies about HA nanomedicines in drug delivery systems, photothermal therapy, photodynamic therapy, diagnostics (because of the high biocompatibility), colloidal stability, and cancer targeting are reviewed for strategies using micelles, nanogels, and inorganic nanoparticles.

scholarly journals Targeting laryngeal cancer cells with 5-fluorouracil and curcumin using mesoporous silica nanoparticles

2020 ◽  
Vol 19 ◽  
pp. 153303382096211
Author(s):  
Ding Wang ◽  
Dan Yu ◽  
Xueshibojie Liu ◽  
Qian Wang ◽  
Xuyang Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mesoporous Silica ◽  
Cell Cycle Arrest ◽  
Silica Nanoparticles ◽  
Cancer Cells ◽  
Laryngeal Cancer ◽  
Synergistic Effects ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carriers ◽  
Cycle Arrest

Objective: To explore the inhibitory and synergistic effects of 5-fluorouracil and curcumin on Hep-2 laryngeal cancer cells and clarify the effect of mesoporous silica nanoparticles as drug carriers. Methods: The inhibitory effects of 5-fluorouracil and curcumin on Hep-2 cells were detected using the CCK-8 assay. CompuSyn was used to calculate the synergistic effect of the 2 drugs. Flow cytometry was used to detect apoptosis and cell cycle arrest induced by 5-fluorouracil and curcumin. The drugs were loaded into mesoporous nanoparticles. Western blotting was used to detect the expression of related proteins after treatment. The growth of subcutaneous tumors in BALB/c nude after the intraperitoneal injection with drug-loaded mesoporous silica nanoparticles was recorded. Results: 5-Fluorouracil and curcumin synergistically induced apoptosis and cell cycle arrest in Hep-2 cells. Mesoporous silica nanoparticles as drug carriers enhanced the therapeutic effects of 5-fluorouracil and curcumin. Conclusions: Mesoporous silica nanoparticles are expected to be effective drug carriers that enhance the synergistic effects of 5-fluorouracil and curcumin on laryngeal cancer.

scholarly journals Active drug targeting

2020 ◽  
Vol 1 ◽  
Author(s):  
J. Erian ◽  
V. Duerrauer ◽  
L. Rainer ◽  
M. Geppert ◽  
I. A. Joubert ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Drug Targeting ◽  
Drug Carriers ◽  
Bowel Cancer ◽  
The Body ◽  
Side Chains ◽  
Layer By Layer ◽  
Iron Oxide Particles ◽  
Specific Organ ◽  
Negative Side Effects

Over 100 years ago, Paul Ehrlich first proposed the side-chain theory to explain how living cells mount an immune response in reaction to an infection. His theory stated that upon the encounter of a threat, cells express side-chains to bind dangerous toxins. These side-chains,cwhich he later named receptors, can break off the cell and circulate throughout the body (i.e. antibodies). Specific antibodies link to particular antigens in the same way that Emil Fischer proposed enzymes bind to their receptors, “as lock and key”. Ehrlich described these so-called “keys” or antibodies as “magic bullets”, which target toxins without harming the body. In recent years, research has focused on using antibodies not only for detection of infection, but also as aids for drug targeting. Thereby, antibodies are bound to the surface of carriers (e.g. nanoparticles) and facilitate a directed transport to a specific organ or site in the body. Aptamer- peptide- or folic acid-doped carriers furthermore have been shown to specifically target cancer cells. By using hydrophilic structures as carriers (e.g. polyethylene glycol), negative side effects esulting from the accumulation of innate proteins can be prevented. Currently, there are drug carriers in the pre-clinical development phase for the treatment of bowel cancer. Thereby, nano polymer capsules coated with a specific antibody are used to target a glycoprotein expressed on bowel cancer cells. The polymers have a size of approximately 500 nm and are produced with a so-called “layer-by-layer” procedure. Once the carrier has reached its target site, the drug needs to be released in a controlled manner. This can be facilitated, for example, by applying a magnetic field in the case of iron oxide particles. Once these particles are taken up by the cells, magnetic radiation can be used to excite the particles, resulting in the rupture of the cell and subsequent cell death.

Control of Cancer Growth Using Two Input Autonomous Fuzzy Nanoparticles

NANO ◽  
2015 ◽  
Vol 10 (04) ◽  
pp. 1550062 ◽  
Author(s):  
Fahimeh Razmi ◽  
Reihaneh Kardehi Moghaddam ◽  
Alireza Rowhanimanesh
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Simple Structure ◽  
Medication Use ◽  
Drug Carriers ◽  
Local Drug Delivery ◽  
Cancer Growth ◽  
Simulation Results

A major challenge in cancer therapy is destroying cancer cells with least side effects on healthy cells. In this paper, autonomous drug-encapsulated nanoparticle (ADENP) with a real feedback control is recommended to prevent from the growth of cancerous tumors and treatment of them. The proposed ADENPs, swarmly perform local drug delivery which leads to significant reduction in side effects on healthy tissues in comparison to global drug delivery. The proposed ADENPs every moment, take feedback directly from drugs and cancer cells and at any time decide how much drugs to release. Also, these ADENPs have the capability of distinguishing unhealthy from healthy tissues, and medication use of these nanoparticles is more efficient than drug carriers. Another feature of these ADENPs is their simple structure in comparison to nanorobots. Simulation results show that ADENPs successfully reduce the number of cancer cells with minimal side effects.

scholarly journals Titania Nanosheets Generates Peroxynitrite for S-Nitrosylation and Enhanced p53 Function in Lung Cancer Cells

2021 ◽  
Author(s):  
Rapeepun Soonnarong ◽  
Sucharat Tungsukruthai ◽  
Bodee Nutho ◽  
Thanyada Rungrotmongkol ◽  
Chanida Vinayanuwattikun ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Lung Cancer ◽  
Molecular Dynamics ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Mechanism Of Action ◽  
Lung Cancer Cells ◽  
Positive Staining ◽  
Apoptosis Induction ◽  
Normal Cells

Abstract Background: Metal oxide nanomaterials are increasingly being exploited in cancer therapy thanks to their unique properties, which can enhance the efficacy of current cancer therapies. However, the nanotoxicity and mechanism of Ti0.8O2 nanosheets for specific site-targeting strategies in NSCLC have not yet been investigated.Methods: The effects of Ti0.8O2 nanosheets on cytotoxicity in NSCLC cells and normal cells were examined. The apoptosis characteristics, including condensed and fragmented nuclei, as assessed by positive staining with annexin V. The cellular uptake of the nanosheets and the induction of stress fiber were assessed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses, respectively. We also evaluated the expression of protein in death mechanism to identify the molecular mechanisms behind the toxicity of these cells. We investigated the relationship between S-nitrosylation and the increase in p53 stability by molecular dynamics.Results: Ti0.8O2 nanosheets caused cytotoxicity in several lung cancer cells, but not in normal cells. The nanosheets could enter lung cancer cells and exert an apoptosis induction. Results for protein analysis further indicated the activation of p53, increased Bax, decreased Bcl-2 and Mcl-1, and activation of caspase-3. The nanosheets also exhibited a substantial apoptosis effect in drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than that of cisplatin and etoposide. In terms of their mechanism of action, we found that the mode of apoptosis induction was through the generation of cellular ONOO− mediated the S-nitrosylation of p53 at C182. Molecular dynamics analysis further showed that the S-nitrosylation of one C182 stabilized the p53 dimer. Consequently, this nitrosylation of the protein led to an upregulation of p53 through its stabilization.Conclusions: Taking all the evidence together, we provided information on the apoptosis induction effect of the nanosheets through a molecular mechanism involving reactive nitrogen species, which affects the protein stability; thus emphasizing the novel mechanism of action of nanomaterials for cancer therapy.

scholarly journals Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769168 ◽  
Author(s):  
Yu-kai Su ◽  
Wen-Chien Huang ◽  
Wei-Hwa Lee ◽  
Oluwaseun Adebayo Bamodu ◽  
Muhammad Ary Zucha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Drug Candidate ◽  
Ovarian Cancer Cells ◽  
Autophagic Flux ◽  
Apoptosis Induction ◽  
Platinum Based Chemotherapy

Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin. We found that cell viability of ovarian cancer cells was decreased through apoptosis induction. Dephosphorylation of Bcl2-associated agonist of cell death protein was increased after methoxyphenyl chalcone treatment that led to activation of caspases. Interestingly, this drug also worked as a G2/M checkpoint modulator with alternative ways of DNA damage signal–evoking potential that might work to increase response after cisplatin treatment. In addition, methoxyphenyl chalcone was able to suppress autophagic flux and stemness regulator in ovarian spheroids that decreased their survival. Therefore, combination of methoxyphenyl chalcone and cisplatin showed synergistic effects. Taken together, we believe that our novel compound is a promising novel therapeutic agent for effective clinical treatment of ovarian cancer.

scholarly journals Aminated Graphene Oxide as a Potential New Therapy for Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Natalia Krasteva ◽  
Milena Keremidarska-Markova ◽  
Kamelia Hristova-Panusheva ◽  
Tonya Andreeva ◽  
Giorgio Speranza ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Graphene Oxide ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Cellular Systems ◽  
Functionalized Graphene Oxide ◽  
The Impact

Nanotechnology-based drug delivery systems for cancer therapy are the topic of interest for many researchers and scientists. Graphene oxide (GO) and its derivates are among the most extensively studied delivery systems of this type. The increased surface area, elevated loading capacity, and aptitude for surface functionalization together with the ability to induce reactive oxygen species make GO a promising tool for the development of novel anticancer therapies. Moreover, GO nanoparticles not only function as effective drug carriers but also have the potential to exert their own inhibitory effects on tumour cells. Recent results show that the functionalization of GO with different functional groups, namely, with amine groups, leads to increased reactivity of the nanoparticles. The last steers different hypotheses for the mechanisms through which this functionalization of GO could potentially lead to improved anticancer capacity. In this research, we have evaluated the potential of amine-functionalized graphene oxide nanoparticles (GO-NH2) as new molecules for colorectal cancer therapy. For the purpose, we have assessed the impact of aminated graphene oxide (GO) sheets on the viability of colon cancer cells, their potential to generate ROS, and their potential to influence cellular proliferation and survival. In order to elucidate their mechanism of action on the cellular systems, we have probed their genotoxic and cytostatic properties and compared them to pristine GO. Our results revealed that both GO samples (pristine and aminated) were composed of few-layer sheets with different particle sizes, zeta potential, and surface characteristics. Furthermore, we have detected increased cyto- and genotoxicity of the aminated GO nanoparticles following 24-hour exposure on Colon 26 cells. The last leads us to conclude that exposure of cancer cells to GO, namely, aminated GO, can significantly contribute to cancer cell killing by enhancing the cytotoxicity effect exerted through the induction of ROS, subsequent DNA damage, and apoptosis.

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