Anticancer Efficiency Research Articles

Schottky Junction Nanozyme Based on Mn-Bridged Co-Phthalocyanines and Ti3C2Tx Nanosheets Boosts Integrative Type I and II Photosensitization for Multimodal Cancer Therapy.

Cancer phototheranostics have the potential for significantly improving the therapeutic effectiveness, as it can accurately diagnose and treat cancer. However, the current phototheranostic platforms leave much to be desired and are often limited by tumor hypoxia. Herein, a Schottky junction nanozyme has been established between a manganese-bridged cobalt-phthalocyanines complex and Ti3C2Tx MXene nanosheets (CoPc-Mn/Ti3C2Tx), which can serve as an integrative type I and II photosensitizer for enhancing cancer therapeutic efficacy via a photoacoustic imaging-guided multimodal chemodynamic/photothermal/photodynamic therapy strategy under near-infrared (808 nm) light irradiation. The Schottky junction not only possessed a narrow-bandgap, enhanced electron-hole separation ability and exhibited a potent redox potential but also enabled improved H2O2 and O2 supplying performances in vitro. Accordingly, the AS1411 aptamer-immobilized CoPc-Mn/Ti3C2Tx nanozyme illustrated high accuracy and excellent anticancer efficiency through a multimodal therapy strategy in in vitro and in vivo experiments. This work presents a valuable method for designing and constructing a multifunctional nanocatalytic medicine platform for synergistic cancer therapy of solid tumors.

PH-dependent, extended release and enhanced in vitro efficiency against colon cancer of Tegafur formulated using chitosan-coated poly(ε-caprolactone) nanoparticles

Tegafur is used to treat various malignant lesions, including advanced gastric and colorectal cancers. However, its efficacy is limited by its low oral bioavailability, short half-life and serious toxicity. To address these drawbacks, a nanoformulation of poly(ε-caprolactone) nanoparticles coated with chitosan was developed for the delivery of Tegafur. Poly(ε-caprolactone) particles were prepared by an interfacial polymer disposition method, while surface functionalization with chitosan followed a coacervation procedure. Transmission electron microscopy and elemental analyses, and electrokinetics of the particles demonstrated that such core/shell nanostructure was obtained. Compared to unmodified particles, chitosan-coated nanoparticles demonstrated a substantially increased stability at both 4 and 25 °C over 30 days. Particles showed an encapsulation efficiency of ≈64% and a pH-dependent behavior in which complete Tegafur release was extended over 168, 48 or 24 h at pH 7.4 (blood), 6.5 (extracellular microenvironment of tumors) or 5.5 (endosomes/lysosomes of tumor cells), respectively. Based on hemocompatibility and cell viability tests, chitosan-coated nanoparticles exhibited satisfactory biocompatibility and safety for drug delivery. Furthermore, Tegafur-loaded chitosan-decorated particles demonstrated enhanced anticancer efficiency, with half maximal inhibitory concentration values in HT-29 and T-84 cells of ≈ 4-fold and ≈3.5-fold less than that of the free drug and drug-loaded unmodified nanoparticles, respectively. In vivo studies are needed to fully assess their efficacy and safety.

The current scenario of furoxan hybrids with anticancer potential

AbstractCancer is one of the most common and deadliest diseases affecting millions of human beings globally. Treatment of cancer has achieved great advancements, and chemotherapy remains one of the most important means. However, the chemotherapy suffers from apparent limitations including drug resistance, systemic toxicity, adverse effects, and tumor recurrence, creating an urgent demand to develop novel anticancer chemotherapeutics. Furoxan derivatives could exert anticancer activity via releasing high concentrations of nitric oxide (NO), which could induce cellular apoptosis, arrest cell cycle, inhibit the migration and invasion of cells, and suppress angiogenesis. Hence, furoxan derivatives demonstrated potent in vitro and in vivo anticancer efficiency. In particular, furoxan hybrids, combination of other anticancer pharmacophores with furoxan moiety, demonstrated significant therapeutic effects on various cancers including drug‐resistant forms since these derivatives could act on multiple targets in cancer cells simultaneously. Accordingly, furoxan hybrids constitute an important source in the development of novel chemotherapeutic agents with anticancer activity. This review is to highlight the current scenario of furoxan hybrids with anticancer potential, covering articles published from 2012 to present. The structure–activity relationships and mechanisms of action are discussed to continuously open up a map for the remarkable exploration of more effective candidates.

PH-sensitive biocompatible chitosan/sepiolite-based cross-linked citric acid magnetic nanocarrier for efficient sunitinib release

In this study, the magnetite nanoparticles were immobilized on the sepiolite needles via co-precipitation of iron ions. Then, the resulted magnetic sepiolite (mSep) nanoparticles were coated with chitosan biopolymer (Chito) in the presence of citric acid (CA) to prepare mSep@Chito core-shell drug nanocarriers (NCs). TEM images showed magnetic Fe3O4 nanoparticles with small sizes (less than 25 nm) on the sepiolite needles. Sunitinib anticancer drug loading efficiencies were ⁓45 and 83.7 % for the NCs with low and high content of Chito, respectively. The in-vitro drug release results exhibited that the mSep@Chito NCs have a sustained release behavior with high pH-dependent properties. Cytotoxic results (MTT assay) showed that the sunitinib-loaded mSep@Chito2 NC had a significant cytotoxic effect on the MCF-7 cell lines. Also, the in-vitro compatibility of erythrocytes, physiological stability, biodegradability, and antibacterial and antioxidant activities of NCs was evaluated. The results showed that the synthesized NCs had excellent hemocompatibility, good antioxidant properties, and were sufficiently stable and biocompatible. Based on the antibacterial data, the minimal inhibitory concentration (MIC) values for mSep@Chito1, mSep@Chito2, and mSep@Chito3 were obtained as 125, 62.5, and 31.2 μg/mL towards S. aureus, respectively. All in all, the prepared NCs could be potentially used as a pH-triggered system for biomedical applications.

Enhanced in vitro and in vivo anticancer activity through the development of Sunitinib-Loaded nanoniosomes with controlled release and improved uptake

This study aims to develop sunitinib niosomal formulations and assess their in-vitro anti-cancer efficiency against lung cancer cell line, A549. Sunitinib, a highly effective anticancer drug, was loaded in the niosome with high encapsulation efficiency. Collagen was coated on the surface of the niosome for enhanced cellular uptake and prolonged circulation time. Different formulations were produced, while response surface methodology was utilized to optimize the formulations. The stability of the formulations was evaluated over a 2-month period, revealing the importance of collagen coating. MTT assay demonstrated dose-dependent cytotoxicity for all formulations against lung cancer cells. Scratch assay test suggested antiproliferative efficacy of the formulations. The flow cytometry data confirmed the improved cytotoxicity with enhanced apoptosis rate when different formulations used. The 2D fluorescent images proved the presence of drug-containing niosomes in the tumor cells. The activation of the apoptotic pathway leading to protein synthesis was confirmed using an ELISA assay, which specifically evaluated the presence of cas3 and cas7. The results of this study indicated the antiproliferative efficacy of optimized niosomal formulations and their mechanism of action. Therefore, niosomes could be utilized as a suitable carrier for delivering sunitinib into lung cancer cells, paving the way for future clinical studies.

PH-Responsive Nano-transferosomes of Purpurin-18 Sodium Salt and Doxorubicin for Enhanced Anticancer Efficiency by Photodynamic and Chemo Combination Therapy.

Cancer is a devastating disease and a major human health concern. Various combination treatments have been developed to combat cancer. To obtain superior cancer therapy, the objective of this study was to synthesize purpurin-18 sodium salt (P18Na) and design P18Na- and doxorubicin hydrochloride (DOX)-loaded nano-transferosomes as a combination of photodynamic therapy (PDT) and chemotherapy for cancer. The characteristics of P18Na- and DOX-loaded nano-transferosomes were assessed, and the pharmacological efficacy of P18Na and DOX was determined using the HeLa and A549 cell lines. The nanodrug delivery system characteristics of the product were found to range from 98.38 to 217.50 nm and -23.63 to -41.10 mV, respectively. Further, the release of P18Na and DOX from nano-transferosomes exhibited a sustained pH-responsive behavior and burst in physiological and acidic environments, respectively. Accordingly, the nano-transferosomes effectively delivered P18Na and DOX into cancer cells, with less leakage in the body, and exhibited pH-responsive release in cancer cells. A photo-cytotoxicity study to HeLa and A549 cell lines revealed a size-dependent anti-cancer effect. These results suggest that the combined nano-transferosomes of P18Na and DOX are effective in the combination of PDT and chemotherapy for cancer.

Fluoropolymer-MOF Hybrids with Switchable Hydrophilicity for 19F MRI-Monitored Cancer Therapy

Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the "stealth-like" nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.

A multi-functional nano-system combining PI3K-110α/β inhibitor overcomes P-glycoprotein mediated MDR and improves anti-cancer efficiency

P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR) in cancers severely limit chemotherapeutic efficacy. We recently reported that phosphatidylinositol-3-kinase (PI3K) 110α and 110β subunits can be novel targets for reversal of P-gp mediated MDR in cancers, and BAY-1082439 as an inhibitor specific for PI3K 110α and 110β subunits could reverse P-gp-mediated MDR by downregulating P-gp expression in cancer cells. However, BAY-1082439 has very low solubility, short half-life and high in-vivo clearance rate. Till now, nano-system with the functions to target PI3K P110α and P110β and reverse P-gp mediated MDR in cancers has not been reported. In our study, a tumor targeting drug delivery nano-system PBDF was established, which comprised doxorubicin (DOX) and BAY-1082439 respectively encapsulated by biodegradable PLGA-SH nanoparticles (NPs) that were grafted to gold nanorods (Au NRs) modified with FA-PEG-SH, to enhance the efficacy to reverse P-gp mediated MDR and to target tumor cells, further, to enhance the efficiency to inhibit MDR tumors overexpressing P-gp. In-vitro experiments indicated that PBDF NPs greatly enhanced uptake of DOX, improved the activity to reverse MDR, inhibited the cell proliferation, and induced S-phase arrest and apoptosis in KB-C2 cells, as compared with free DOX combining free BAY-1082439. In-vivo experiments further demonstrated that PBDF NPs improved the anti-tumor ability of DOX and inhibited development of KB-C2 tumors. Notably, the metastasis of KB-C2 cells in livers and lungs of nude mice were inhibited by treatment with PBDF NPs, which showed no obvious in-vitro or in-vivo toxicity.

Design and synthesis of γ‐Fe2O3@Ag‐S‐CH2‐COOH nanocatalyst for one‐pot synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones and their anti‐skin cancer activity

The ongoing work describes the catalytic evaluation of γ‐Fe2O3@Ag‐S‐CH2‐COOH magnetic nanoparticles utilizing γ‐Fe2O3 obtained from waste iron rust for one‐pot synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones. As‐prepared γ‐Fe2O3@Ag‐S‐CH2‐COOH nanoparticles were characterized by Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDX), dynamic light scattering (DLS), transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), and Brunauer–Emmett–Teller (BET) technique. The catalytic performance of greener γ‐Fe2O3@Ag‐S‐CH2‐COOH nanoparticles was utilized in the synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones. The excellent catalytic performance was shown by magnetic nanoparticles in addition to its ease of separation by an external magnet and can be recycled for five consecutive turns without significant loss of catalytic activity. Furthermore, the synthesized 2,3‐dihydroquinazolin‐4(1H)‐ones were confirmed by FT‐IR, 1H, 13C nuclear magnetic resonance (NMR), and mass spectrometry. Moreover, the synthesized 2,3‐dihydroquinazolin‐4(1H)‐ones were evaluated for their anticancer efficiency against the human skin cancer cell line B16F10 along with molecular docking investigation.

NIR-light-responsive chemo-photothermal hydrogel system with controlled DOX release and photothermal effect for cancer therapy

Here a multiplex near-infrared (NIR) light-responsive hydrogel platform (SA/DOX@hydrogel) has been constructed for controlled synergetic chemotherapy and photothermal cancer therapy. Ag nanoparticles doped SnS2 nanoflowers (SA), which can convert NIR light into thermal energy with efficiency of 30.0%, were embedded in low-melting-temperature agarose hydrogel as a photothermal agent. Moreover, anticancer drug doxorubicin (DOX) is loaded into the hydrogel for tumor treatment. The heat generated from NIR irradiation of SA promotes melting of hydrogel, thus the incorporated DOX can be released into the surrounding environment. By adjusting the irradiation power and time, the drug will be released with a control. In vitro study shows that the SA/DOX@hydrogel system is highly effective to kill cancer cells (∼ 93%) at a relatively low -laser irradiation (1.2 w cm−2, 10 min) treatment. In the mice tumor model, SA/DOX@hydrogel with laser irradiation is capable to suppress or even eliminate the tumor completely from the mice within two weeks. The excellent anti-cancer efficiency benefits from the combined results of photothermal effect from NIR-irradiated SA and chemotherapy from DOX controlled release by heat. Therefore, this chemo-photothermal therapeutic system exhibits a great potential for cancer treatment.

Aspergillus terreus camptothecin-sodium alginate/titanium dioxide nanoparticles as a novel nanocomposite with enhanced compatibility and anticancer efficiency in vivo

BackgroundCamptothecin derivatives are one of the most prescribed anticancer drugs for cancer patients, however, the availability, efficiency, and water solubility are the major challenges that halt the applicability of this drug.MethodsBiosynthetic potency of camptothecin by Aspergillus terreus, open a new avenue for commercial camptothecin production, due to their short-life span, feasibility of controlled growth conditions, and affordability for higher growth, that fulfill the availability of the scaffold of this drug.ResultsCamptothecin (CPT) was purified from the filtrates of A. terreus, and their purity was checked by HPLC, and its chemical structure was verified by LC/MS, regarding to the authentic one. To improve the anticancer efficiency of A. terreus CPT, the drug was conjugated with sodium alginate (SA)/Titanium dioxide nanoparticles (TiO2NPs) composites, and their physicochemical properties were assessed. From the FT-IR profile, a numerous hydrogen bond interactions between TiO2 and SA chains in the SA/TiO2 nanocomposites, in addition to the spectral changes in the characteristic bands of both SA/TiO2 and CPT that confirmed their interactions. Transmission electron microscopy analysis reveals the spherical morphology of the developed SA/TiO2NPs nanocomposite, with the average particle size ~ 13.3 ± 0.35 nm. From the results of zeta potential, successful loading and binding of CPT with SA/TiO2 nanocomposites were observed.ConclusionThe in vivo study authenticates the significant improvement of the antitumor activity of CPT upon loading in SA/TiO2 nanocomposites, with affordable stability of the green synthesized TiO2NPs with Aloe vera leaves extract.

Facile construction of irinotecan loaded mesoporous nano-formulation with surface-initiated polymerization to improve stimuli-responsive drug delivery for breast cancer therapy

This work uses rice husk to fabricate mesoporous silica nanoparticles (D-RMN) for breast cancer therapy. The biocompatible dual-responsive (DAN-RMN) was developed by polymerizing acrylic acid (AA) and n-isopropyl acrylamide (NIPAM) on the DV-RMN surface monomeric ratio to increase drug delivery efficiency after vinyl groups were added to the surface of nanoparticles (DAN-RMN). Various analytical and spectroscopical methods characterized the fabricated nanoparticles. Additionally, further encapsulation with SN-38 into the DAN-RMN enhances anticancer efficiency. The in-vitro controlled SN-38 release displayed remarkable temperature and pH response. The MTT assay established the biocompatibility and cytotoxicity of natural sources of silica and DAN-RMN. The fabricated SN-38@DAN-RMN nanoparticles effectively killed the MDA-MB-231 and 4T1 cancerous cells, confirmed by the MTT assay. The IC50 values of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 1.8 μg/mL and 1.7 μg/mL, respectively. In addition, acridine orange-ethidium bromide (AO-EB) dual staining methods were used to determine morphological changes of cell shrinkage and fragmentation. Nuclear staining methods confirmed the nuclear fragmentation and condensation of the cells. Further, the cell death was examined using dual staining Annexin V-FITC/PI in flow cytometric analyses to assess apoptosis in the MDA-MB-231 and 4T1 cell lines. The apoptotic cell ratio of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 27.8 and 32.8, respectively. Since there is no drug leakage in the blood while the carrier is in circulation, the DAN-RMN nanocarrier may be used for targeted and stimuli-responsive administration using ultrasound imaging.

Anticancer Effects of Gut Microbiota-Derived Short-Chain Fatty Acids in Cancers.

Short-chain fatty acids (SCFAs), such as butyrate, propionate, and acetate produced by the gut microbiota have been implicated in physiological responses (defense mechanisms, immune responses, and cell metabolism) in the human body. In several types of cancers, SCFAs, especially butyrate, suppress tumor growth and cancer cell metastasis via the regulation of the cell cycle, autophagy, cancer-related signaling pathways, and cancer cell metabolism. In addition, combination treatment with SCFAs and anticancer drugs exhibits synergistic effects, increasing anticancer treatment efficiency and attenuating anticancer drug resistance. Therefore, in this review, we point out the importance of SCFAs and the mechanisms underlying their effects in cancer treatment and suggest using SCFA-producing microbes and SCFAs to increase therapeutic efficacy in several types of cancers.

Human umbilical cord blood-mesenchymal stem cell derived exosomes as an efficient nanocarrier for Docetaxel and miR-125a: Formulation optimization and anti-metastatic behaviour

AimExosomes, as a nanocarrier for the co-delivery of biologicals and small anticancer molecules is yet in its infancy. Herein, we investigated hUCBMSC derived exosomes as a biogenic nanocarrier for the co-delivery of tumor suppressor miR-125a and microtubule destabilizing Docetaxel (DTX) to target the proliferative and migratory aggressiveness of the murine TNBC 4T1 cells. Main methodsIn this study, hUCBMSCs from the human umbilical cord blood cells (hUCB) were successfully transfected with miR-125a. Thereafter, DTX was encapsulated into both non-transfected and transfected exosomes by optimized mild sonication-incubation technique. The anticancer efficiency of hUCBMSC Exo-DTX and miR-125a Exo-DTX was compared by MTT and morphometric assay. The prominent anti-metastatic behaviour of the latter was confirmed by in-vitro wound healing and transwell invasion assay. Further, the synergistic effect of miR-125a and DTX was confirmed by F-actin and nuclear degradation by confocal and FESEM assay. Key findingshUCBMSC exosomes exhibited DTX payload of 8.86 ± 1.97 ng DTX/ μg exosomes and miRNA retention capacity equivalent to 12.31 ± 5.73 %. The co-loaded formulation (miR-125a Exo-DTX) exhibited IC50 at 192.8 ng/ml in 4T1 cells, which is almost 2.36 folds' lower than the free DTX IC50 (472.8 ng/ml). Additionally, miR-125a Exo-DTX treatment caused wound broadening upto 6.14±0.38 % while treatment with free DTX and miR-125a exosomes alone caused 18.71±4.5 % and 77.36±10.4 % of wound closure respectively in 36 h. miR-125a Exo-DTX treatment further exhibited significantly reduced invasiveness of 4T1 cells (by 3.5 ± 1.8 %) along with prominent cytoskeletal degradation and nuclear deformation as compared to the miR-125a exosomes treated group. The miR-125a expressing DTX loaded exosomal formulation clearly demonstrated the synergistic apoptotic and anti-migratory efficiency of the miR-125a Exo-DTX. SignificanceThe synergistic anticancer and anti-metastatic effect of miR-125a Exo-DTX was observed due to presence of both DTX and miR-125a as the cargo of hUCBMSC derived exosomes.

Design, synthesis, and antitumor evaluation of morpholine substituted bisnaphthalimides as DNA targeting agents

A series of mono- and bisnaphthalimides derivatives containing 3-nitro and 4-morpholine moieties were designed, synthesized, and evaluated for their in vitro anticancer activities against four cancer cell lines. Some compounds exhibited relatively good antiproliferative activity on the cell lines tested, in comparison with mitonafide and amonafide. It is noteworthy that bisnaphthalimide A6 was identified as the most potent compound in anti-proliferation against MGC-803 cells, with an IC50 lowered to 0.09 μM, a far greater potency than that of mono-naphthalimide A7, mitonafide, and amonafide. A gel electrophoresis assay revealed that DNA and Topo I were the potential targets of compounds A6 and A7. The treatment of CNE-2 cells with compounds A6 and A7 resulted in an S phase cell cycle arrest, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of CDK2 and cyclin E. In addition, compounds A6 and A7-induced apoptosis was further confirmed by flow cytometry, ROS generation assay, and Hoechst 33,258 staining. In particular, in vivo antitumor assay results revealed that bisnaphthalimide A6 exhibited potent anticancer efficiency in an MGC-803 xenograft tumor model, in comparison with mitonafide, and had lower toxicity than mono-naphthalimide A7. In brief, the results suggested that bisnaphthalimide derivatives containing 3-nitro and 4-morpholine moieties might serve as DNA binding agents for the development of new antitumor agents.

Efficient synthesis and anticancer evaluation of spider toxin peptide LVTX-8-based analogues with enhanced stability

Cytotoxic peptides derived from spider venoms have been considered as promising candidates for anticancer treatment. The novel cell penetrating peptide LVTX-8, which is a 25-residue amphipathic α-helical peptide isolated from spider Lycosa vittata, exhibited potent cytotoxicity and is a potential precursor for further anticancer drug development. Nevertheless, LVTX-8 may be easily degraded by multiple proteases, inducing the proteolytic stability problem and short half-life. In this study, ten LVTX-8-based analogs were rationally designed and the efficient manual synthetic method was established by the DIC/Oxyma based condensation system. The cytotoxicity of synthetic peptides was systematically evaluated against seven cancer cell lines. Seven of the derived peptides exhibited high cytotoxicity towards tested cancer in vitro, which was better than or comparable to that of natural LVTX-8. In particular, both N-acetyl and C-hydrazide modified LVTX-8 (825) and the conjugate methotrexate (MTX)-GFLG-LVTX-8 (827) possessed more durable anticancer efficiency, higher proteolytic stability, as well as lower hemolysis. Finally, we confirmed that LVTX-8 could disrupt the integrity of cell membrane, target the mitochondria and reduce the mitochondrial membrane potential to induce the cell death. Taken together, the structural modifications were conducted on LVTX-8 for the first time and the stability significantly improved derivatives 825 and 827 may provide useful references for the modifications of cytotoxic peptides.

Copperphosphotungstate Doped Polyanilines Nanorods for GSH-Depletion Enhanced Chemodynamic/NIR-II Photothermal Synergistic Therapy.

The high concentration of glutathione (GSH) and hydrogen peroxide (H2O2) levels within the tumor microenvironment (TME) are the major obstacle to induce the unsatisfactory anticancer treatment efficiency. The synergistic cancer therapy strategies of the combination the GSH depletion enhanced chemodynamic therapy (CDT) with photothermal therapy (PTT) have been proved to be the promising method to significantly improve the therapeutic efficacy. The copperphosphotungstate was incorporated into polyanilines to design copperphosphotungstate doped polyaniline nanorods (CuPW@PANI Nanorods) via chemical oxidant polymerization of aniline. The low long-term toxicity and biocompatibility were evaluated. Both in vitro and in vivo experiments were carried out to confirm the GSH depletion enhanced CDT/NIR-II PTT synergistic therapy. CuPW@PANI Nanorods feature biosafety and biocompatibility, strong NIR-II absorbance, and high photothermal-conversion efficiency (45.14%) in NIR-II bio-window, making them highly applicable for photoacoustic imaging and NIR-II PTT. Moreover, CuPW@PANI Nanorods could consume endogenous GSH to disrupt redox homeostasis and perform a Fenton-like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Furthermore, NIR-II photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT, which realizes high therapeutic efficacy in vivo. This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.

The Novel 5-Fluorouracil Loaded Ruthenium-based Nanocarriers Enhanced Anticancer and Apoptotic Efficiency while Reducing Multidrug Resistance in Colorectal Cancer Cells.

Recently, nanocarriers have been made to eliminate the disadvantages of chemotherapeutic agents by nanocarriers. Nanocarriers show their efficacy through their targeted and controlled release. In this study, 5-fluorouracil (5FU) was loaded into ruthenium (Ru)-based nanocarrier (5FU-RuNPs) for the first time to eliminate the disadvantages of 5FU, and its cytotoxic and apoptotic effects on HCT116 colorectal cancer cells were compared with free 5FU. 5FU-RuNPs with a size of approximately 100nm showed a 2.61-fold higher cytotoxic effect compared to free 5FU. Apoptotic cells were detected by Hoechst/propidium iodide double staining, and the expression levels of BAX/Bcl-2 and p53 proteins, in which apoptosis occurred intrinsically, were revealed. In addition, 5FU-RuNPs was also found to reduce multidrug resistance (MDR) according to BCRP/ABCG2 gene expression levels. When all the results were evaluated, the fact that Ru-based nanocarriers alone did not cause cytotoxicity proved that they were ideal nanocarriers. Moreover, 5FU-RuNPs did not show any significant effect on the cell viability of normal human epithelial cell lines BEAS-2B. Consequently, the 5FU-RuNPs synthesized for the first time may be ideal candidates for cancer treatment because they can minimize the potential drawbacks of free 5FU.

Anticancer Potential of Artemisinin Derivative-Dihydroartemisinin

Artemisinin is famous for its effectiveness of treating malaria for years. Potential of artemisinin in treating cancer has been recently recognized. In this study, the anticancer potential of artemisinin and its derivative dihydroartemisinin (DHA) is comprehensively illustrated, including brief introduction of background and clinical applications. Artemisinin derivatives, especially dihydroartemisinin, of which the anticancer mechanism such as induction of apoptosis, inhibition of peripheral blood vessels has also been depicted. Cases of clinical study of cervical cancer and breast cancer are also reported to further proof the anticancer efficiency of dihydroartemisinin. Finally, summary of perspectives and significance of artemisinin and DHA is also provided.

Anticancer Activity of Synthesized ZnO and ZnO/AgCl Nanocomposites against Five Human Cancer Cells

In this work, a refluxing method is used to prepare nanoparticles of zinc oxide (ZnO NPS) and zinc oxide /silver chloride nanocomposites (ZnO/AgCl NCS). The structural properties of nanocrystals are studied by Atomic Force Microscope (AFM), X-Ray Diffraction (XRD), and Field Emission Scanning Electron Microscopy (FE-SEM) to determine the average crystal size, morphology, particle size and average grain size of nanocrystals. The results of anticancer efficiency of ZnO NPs and ZnO/AgCl NCs show cytotoxic activity against five human cancer cells, namely hepatocellular carcinoma, rhabdomyosarcoma (RD), colorectal carcinoma (HCT116), mammary gland (MCF-7), and epidermoid carcinoma (Hep2) compared against doxorubicin. The anticancer mechanism of pure and nanocomposites ZnO are suggested according to the release of Zn+2 and the production of reactive oxidation species (ROS) and the effect of these species on cancer inhibition.