Promising Applications In Cancer Therapy Research Articles

Pulsed electromagnetic therapy in cancer treatment: Progress and outlook

AbstractCancer is one of the major diseases that endanger human health. Current treatment options have low patient tolerance, poor prognosis, and strong side effects. Pulsed electromagnetic therapy can selectively kill cancer cells by taking advantage of their own electromagnetic sensitivity specificity. Pulsed electric fields (PEFs), pulsed electromagnetic fields (PEMFs), and cold atmospheric plasma (CAP) are three main means that have promising application in cancer therapy. Pulsed electromagnetic therapy showed significant anticancer ability in vitro and in vivo. In this paper, we summarize the basic principles, methods, and state of art research of PEFs, PEMFs, and PEMFs for cancer therapy. Based on cancer pro‐oxidation therapy, we propose a combination therapy of electromagnetic field‐enhanced CAP for cancer therapy.

Calcium-Differentiated Cellular Internalization of Allosteric Framework Nucleic Acids for Targeted Payload Delivery.

Target delivery systems have extensively shown promising applications in cancer therapy, and many of them function smartly by responding to the cancer cell microenvironment. Here, we for the first time report Ca2+-differentiated cellular internalization of 2D/3D framework nucleic acids (FNAs), enabling the engineering of a conceptually new target delivery system using an allosteric FNA nanovehicle. The FNA vehicle is subject to a 2D-to-3D transformation on the cancer cell surface via G-quadruplexes responding to environmental K+ and thereby allows its cell entry to be more efficiently promoted by Ca2+. This design enables the FNA vehicle to target cancer cells and selectively deliver an antisense strand-containing cargo for live-cell mRNA imaging. It would open new avenues toward targeted drug delivery and find extensive applications in precise disease treatment.

Coordinating External and Built-In Triggers for Tunable Degradation of Polymeric Nanoparticles via Cycle Amplification.

The selective activation of nanovectors in pathological tissues is of crucial importance to achieve optimized therapeutic outcomes. However, conventional stimuli-responsive nanovectors lack sufficient sensitivity because of the slight difference between pathological and normal tissues. To this end, the development of nanovectors capable of responding to weak pathological stimuli is of increasing interest. Herein, we report the fabrication of amphiphilic polyurethane nanoparticles containing both external and built-in triggers. The activation of external triggers leads to the liberation of highly reactive primary amines, which subsequently activates the built-in triggers with the release of more primary amines in a positive feedback manner, thereby triggering the degradation of micellar nanoparticles in a cycle amplification model. The generality and versatility of the cycle amplification concept have been successfully verified using three different triggers including reductive milieu, light irradiation, and esterase. We demonstrate that these stimuli-responsive nanoparticles show self-propagating degradation performance even in the presence of trace amounts of external stimuli. Moreover, we confirm that the esterase-responsive nanoparticles can discriminate cancer cells from normal ones by amplifying the esterase stimulus that is overexpressed in cancer cells, thereby enabling the selective release of encapsulated payloads and killing cancer cells. This work presents a robust strategy to fabricate stimuli-responsive nanocarriers with highly sensitive property toward external stimuli, showing promising applications in cancer therapy with minimized side effects.

Construction and evaluation of red blood cells-based drug delivery system for chemo-photothermal therapy

In this study, a novel tumor-targeting drug delivery system (DDS) based on red blood cells (RBCs) were fabricated for combinational chemo-phototherapy against cancer. Cyclic peptide (cRGD) and indocyanine green (ICG) were applied to the surface of RBCs to increase the targeting and photothermal effect, respectively. Doxorubicin (DOX) as a model drug was loaded into RBCs by the hypotonic dialysis method. A series of tests have been carried out to evaluate the RBCs-based DDS and these tasks include physicochemical properties, cellular uptake, targeting ability, and combination therapeutic efficiency. As a result, the DOX was successfully loaded into RBCs and the drug loading amount was 0.84 ± 0.09 mg/mL. There was no significant change of particle size after surface modification of RBCs. The RBCs-based DDS could target to the surface of cancer cells, which delivery DOX to the lesions efficiently and accurately. Meanwhile, due to the combined treatment effect, the RBCs-based DDS can effectively inhibit tumor growth. The RBCs-based DDS constructed in this research may have promising applications in cancer therapy due to their highly synergistic efficient therapy and to investigate its possibility for tumor therapy.

Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53.

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy.

Synthesis and characterisation of novel biopolymer stabilised organic Pt-nanocomposite: assessment of its antioxidant and antitumour properties.

Green synthesis of organic Pt-nanocomposite was accomplished using carboplatin as a precursor and novel biopolymer - gum kondagogu (GK) as a reducing agent. The synthesised GK stabilised organic Pt-nanocomposite (GKCPt NC) was characterised by different analytical techniques such as ultraviolet-visible spectroscopy, nanoparticle analyser, scanning electron microscopy and energy dispersive X-ray analysis, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma optical emission spectrophotometer. The XRD pattern established the amorphous nature of GKCPt NC. TEM analysis revealed the homogeneous, monodisperse and spherical nature, with Pt metal size of 3.08 ± 0.62 nm. The binding energy at 71.2 and 74.6 eV show the presence of metallic platinum, Pt(0) confirmed by XPS studies. Further, in vitro radical scavenging and antitumour activity of GKCPt NC have been investigated. In comparison to GK and carboplatin, GKCPt NC showed superior 1, 1-diphenyl-2-picrylhydrazyle activity of 87.82%, whereas 2, 2-azinobis-(3-ethylbenzthinzoline-6-sulphonic acid) activity was 38.50%, respectively. In vitro studies of the antitumour property of GK, GKCPt NC and carboplatin were evaluated by potato disc tumour bioassay model. The efficacy of synthesised GKCPt NC concentration (IC50) on tumour inhibition was found to be 2.04-fold lower as compared to carboplatin. Overall, the synthesised GKCPt NC shows both antitumour and antioxidant properties when compared to the original drug - carboplatin and might have promising applications in cancer therapy.

Cold Plasma with Immunomodulatory Properties Has Significant Anti-Lymphoma Activities in Vitro and In Vivo

In recent years, cancer immunotherapy has revolutionized cancer care. Remarkable clinical efficacy and durable responses to checkpoint blockade antibodies or to genetically engineered T-cells (CAR T cell) have been observed in patients with multiple cancers. However, not all cancer patients benefit from these therapies and as such novel immunotherapeutic approaches are needed. The cold atmospheric plasma (CAP) is a form of near room temperature ionized gas, which has shown a promising application in cancer therapy given its antitumor effects in vitro as well as in vivo. For the first time, we have shown that upon CAP treatment, the viability of the immune cells remained unaffected. Strikingly, we observed a significantly stronger immune activation of those CAP treated cells when compare with helium gas control. First, we have demonstrated that even without LPS stimulation, in vitro exposure of peritoneal elicited macrophages (PEM) to CAP for 15 or 30 seconds was sufficient to trigger the production of the pro-inflammatory cytokines IL-12 and IL-6. In addition, decreased production of anti-inflammatory cytokine IL-10 and diminished the expression of PD-L1 were observed in CAP-treated PEM as well. It indicated that CAP treatment may potentially facilitate PEMs as better activator of T cells. Second, in lieu of the stimulatory effects of CAP upon PEM, we asked whether CAP could enhance T-cell activation. So we isolated T cells from spleens of C57BL/6 mice and exposed these T cells to CAP followed by anti-CD3/CD28 stimulation. Our study shown that the production of IL-2 and IFN-g were significantly increased by T-cells treated with CAP as compared with helium gas control. Furthermore, to gain insights into effects of CAP upon immune responses in vivo, we isolated lymph nodes from OTII mice and directly exposed these LNs with CAP, helium gas control or left untreated. Then CD4+ T cells were further isolated from the LNs and cultured with macrophages in the presence or absence of OVA peptide for 48 hours, respectively. Surprisingly, CD4+ T cells isolated from CAP-treated LNs displayed enhanced function indicated by its increased production of IL-2 and IFN-g. More importantly, strong in vivo anti-tumor effects were observed when adoptively transfer CAP exposed T cells to lymphoma bearing animals. Taken together, we have shown for the first time an elevated immune-stimulatory effect of CAP upon both APCs and T cells in vitro and in vivo. Our finding may potentially shed light of a novel therapeutic approach for future cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.

Facile synthesis of yolk-shell structured Fe3O4@C-Au nanoparticles for thermotherapic application

Abstract Yolk-shell nanostructures haves promising applications in cancer therapy due to their great potential for multi-functions. However, the control over its structure and morphology still remains a big challenge. Herein, yolk-shell Fe3O4@C-Au composite nanostructure has been successfully synthesized with magnetic Fe3O4 nanoparticles encapsulated in hollow carbon shells and Au nanoparticles well dispersed. The yolk-shell structure has a uniform size of ~80 nm and a high surface area of 325.13 m2/g. The Fe3O4 and Au nanoparticles are 10 and 3 nm, respectively. The as-prepared Fe3O4@C-Au showed good biocompatibility during endocytosis process. The Fe3O4@C-Au suspension (150 μg/ml) shows efficient photothermal conversion effect and effectively damage 4T1 cells. The composite nanostructure Fe3O4@C-Au show promising applications in cancer diagnosis and therapy.

Influence of taxol and CNTs on the stability analysis of protein microtubules

Microtubules are used as targets for anticancer drugs due to their crucial role in the process of mitosis. Recent studies show that carbon nanotubes (CNTs) can be classified as microtubule-stabilizing agents as they interact with protein microtubules (MTs), leading to interference in the mitosis process. CNTs hold a substantial promising application in cancer therapy in conjunction with other cancer treatments such as radiotherapy and chemotherapy. In the current study, a size-dependent model is developed for the stability analysis of CNT-stabilized microtubules under radial and axial loads. A nonlocal shell theory with strain gradient effects is employed to take size influences into account. Moreover, Van der Waals interactions between CNTs and MTs are simulated. An excellent agreement is observed between the present model and reported data from experiments on protein MTs. In addition, the effects of taxol, as another stabilizing agent, on the stability of microtubules are studied. It is found that both nonlocal and strain gradient effects are essential to accurately obtain the stability capacity of MTs. Furthermore, CNTs have an increasing effect on the critical loads of microtubules while the critical loads reduce in the presence of taxol.

Photodynamic PEG-coated ROS-sensitive prodrug nanoassemblies for core-shell synergistic chemo-photodynamic therapy

The combination of chemotherapy with photodynamic therapy (PDT) holds promising applications in cancer therapy. However, co-encapsulation of chemotherapeutic agents and photosensitizers (PS) into the conventional nanocarriers suffers from inefficient co-loading and aggregation-caused quenching (ACQ) effect of PS trapped in dense carrier materials. Herein, we report a light-activatable photodynamic PEG-coated prodrug nanoplatform for core–shell synergistic chemo-photodynamic therapy. A novel photodynamic polymer is rationally designed and synthesized by conjugating pyropheophorbide a (PPa) to polyethylene glycol 2000 (PEG2k). PPa is used as the hydrophobic and photodynamic moiety of the amphipathic PPa-PEG2k polymer. Then, a core–shell nanoassembly is prepared, with an inner core of a reactive oxygen species (ROS)-responsive oleate prodrug of paclitaxel (PTX) and an outer layer of PPa-PEG2k. PPa-PEG2k serves for both PEGylation and PDT. Instead of being trapped in the inner core, PPa in the outer PPa-PEG2k layer significantly alleviates the ACQ effect. Under laser irradiation, ROS generated by PPa-PEG2k not only is used for PDT but also synergistically promotes PTX release in combination with the endogenous ROS overproduced in tumor cells. The photodynamic PEG-coated nanoassemblies demonstrated synergistic antitumor activity in vivo. Such a unique nanoplatform, with an inner chemotherapeutic core and an outer photodynamic PEG shell, provides a new strategy for synergistic chemo-photodynamic therapy. Statement of SignificationThe combination of chemotherapy with photodynamic therapy (PDT) holds promising prospects in cancer therapy. However, it remains a tremendous challenge to effectively co-deliver chemotherapeutic drugs and photosensitizers into tumors. Herein, we construct a photodynamic PEGylation-coated prodrug-nanoplatform for high-efficiency synergistic cancer therapy, which is composed of a light-activatable PPa-PEG2k shell and a ROS-responsive paclitaxel (PTX) prodrug core. The PPa-PEG2k-generated ROS not only was used for synergistic PTX release but also synergistically facilitated tumor cell apoptosis in combination with PTX-initiated chemo-cytotoxicity. The light-activatable nanoassemblies exhibited multiple drug delivery advantages including high co-loading efficiency, self-enhanced PTX release, extended circulation time, favorable biodistribution, and potent synergistic anticancer activity. Our findings provide a new strategy for the rational design of advanced nano-DDS for high-efficiency combinational chemo-photodynamic therapy.

Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells

Over the past decade, cold atmospheric plasmas have shown promising application in cancer therapy. The therapeutic use of plasma-activated media is a topic addressed in an emerging field known as plasma pharmacy. In oncology, plasma-activated media are used to harness the therapeutic effects of oxidant species when they come in contact with cancer cells. Among several factors that contribute to the anticancer effect of plasma-activated liquid media (PALM), H2O2 and NO derivatives likely play a key role in the apoptotic pathway. Despite the significant amount of literature produced in recent years, a full understanding of the mechanisms by which PALM exert their activity against cancer cells is limited. In this paper, a sealed dielectric-barrier discharge was used to disentangle the effect of reactive nitrogen species (RNS) from that of reactive oxygen species (ROS) on cancer cells. Two cancers characterized by poor prognosis have been investigated: metastatic melanoma and pancreatic cancer. Both tumour models exposed to PALM rich in H2O2 showed a reduction in proliferation and an increase in calreticulin exposure and ATP release, suggesting the potential use of activated media as an inducer of immunogenic cell death via activation of the innate immune system.

Photodynamic PEGylation Coated Prodrug-Nanoassemblies for Core-Shell Synergistic Chemo-Photodynamic Therapy

Combination of chemotherapy with photodynamic therapy (PDT) holds promising applications in cancer therapy. However, co-encapsulation of chemotherapeutic agents and photosensitizers (PS) into the conventional nanocarriers suffers from inefficient co-loading and aggregation-caused quenching (ACQ) effect of PS trapped in dense carrier materials. Herein, we report a light-activatable photodynamic PEGylation-coated prodrug-nanoplatform for core-shell synergistic chemo-photodynamic therapy. A novel photodynamic polymer is rationally designed and synthesized by conjugating pyropheophorbide a (PPa) to polyethylene glycol 2000 (PEG2k). PPa is used as the hydrophobic and photodynamic moiety of the amphipathic PPa-PEG2k polymer. Then, a core-shell nanoassemblies is prepared, with an inner core of a reactive oxygen species (ROS)-responsive oleate prodrug of paclitaxel (PTX) and an outer layer of PPa-PEG2k. PPa-PEG2k serves both for PEGylation modification and PDT. Instead of being trapped in the inner core, PPa in the outer PPa-PEG2k layer significantly alleviates the ACQ effect. Under laser irradiation, ROS generated by PPa-PEG2k is not only used for PDT, but also synergistically promotes PTX release in combination with the endogenous ROS overproduced in tumor cells. The photodynamic PEGylation coated nanoassemblies demonstrated synergistic antitumor activity in vivo. Such a unique nanoplatform, with an inner chemotherapeutic core and an outer photodynamic PEGylation shell, provides a new strategy for synergistic chemo-photodynamic therapy.

Low Power Single Laser Activated Synergistic Cancer Phototherapy Using Photosensitizer Functionalized Dual Plasmonic Photothermal Nanoagents.

Combination therapy, especially photodynamic/photothermal therapy (PDT/PTT), has shown promising applications in cancer therapy. However, sequential irradiation by two different laser sources and even the utilization of single high-power laser to induce either combined PDT/PTT or individual PTT will be subjected to prolonged treatment time, complicated treatment process, and potential skin burns. Thus, low power single laser activatable combined PDT/PTT is still a formidable challenge. Herein, we propose an effective strategy to achieve synergistic cancer phototherapy under low power single laser irradiation for short duration. By taking advantage of dual plasmonic PTT nanoagents (AuNRs/MoS2), a significant increase in temperature up to 60 °C with an overall photothermal conversion efficiency (PCE) of 68.8% was achieved within 5 min under very low power (0.2 W/cm2) NIR laser irradiation. The enhanced PCE and PTT performance is attributed to the synergistic plasmonic PTT effect (PPTT) of dual plasmonic nanoagents, promoting simultaneous release (85%) of electrostatically bonded indocyanine green (ICG) to induce PDT effects, offering simultaneous PDT/synergistic PPTT. Both in vitro and in vivo investigations reveal complete cell/tumor eradication, implying that simultaneous PDT/synergistic PPTT effects induced by AuNRs/MoS2-ICG are much superior over individual PDT or synergistic PPTT. Notably, synergistic PPTT induced by dual plasmonic nanoagents also demonstrates higher in vivo antitumor efficacy than either individual PDT or PTT agents. Taken together, under single laser activation with low power density, the proposed strategy of simultaneous PDT/synergistic PPTT effectively reduces the treatment time, achieves high therapeutic index, and offers safe treatment option, which may serve as a platform to develop safer and clinically translatable approaches for accelerating cancer therapeutics.

Transferrin-targeting redox hyperbranched poly(amido amine)-functionalized graphene oxide for sensitized chemotherapy combined with gene therapy to nasopharyngeal carcinoma

A drug and gene co-delivery system with chemotherapeutic sensibilization was prepared and used for nasopharyngeal carcinoma therapy. For this purpose, the graphene oxide (GO) was conjugated with the redox hyperbranched poly(amido amine) (HPAA) and then the targeting molecule, transferrin (Tf), was also conjugated. The obtained Tf-HPAA-GO could co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid (pMMP-9) effectively and showed the targeting effect to HNE-1 cells. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency. Besides that, Tf-HPAA-GO/DOC also showed the chemotherapeutic sensibilization effect, the formulation containing HPAA segments showed much higher cytotoxicity than free DOC. Benefiting from the sensibilization effect and DOC/pMMP-9 co-delivery strategy, this Tf-HPAA-GO/DOC/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. This strategy provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization, and targeting into one single platform, which showed a promising application in cancer therapy.

Improving anticancer activity towards colon cancer cells with a new p53-activating agent.

Impairment of the tumour suppressor p53 pathway is a major event in human cancers, making p53 activation one of the most attractive therapeutic strategies to halt cancer. Here, we have identified a new selective p53 activator and investigated its potential as an anticancer agent. Anti-proliferative activity of the (R)-tryptophanol-derived bicyclic lactam SYNAP was evaluated in a range of human cancer cells with different p53 status. The anticancer activity and mechanism of action of SYNAP was studied in two- and three-dimensional models of human colon adenocarcinoma HCT116 cells with wild-type p53 and corresponding p53-null isogenic derivative cells, alone and in combination with known chemotherapeutic agents. SYNAP showed anti-proliferative effect in human cancer cells dependent on p53 status. In HCT116 cells, SYNAP caused p53-dependent growth inhibition, associated with cell cycle arrest and apoptosis, anti-migratory activity and regulation of the expression of p53 transcriptional targets. Data also indicated that SYNAP targeted p53, inhibiting its interaction with its endogenous inhibitors, murine double minute (MDM)2 and MDMX. Moreover, SYNAP sensitized colon cancer cells to the cytotoxic effect of known chemotherapeutic agents. SYNAP did not induce acquired or cross-resistance and re-sensitized doxorubicin-resistant colon cancer cells to chemotherapy. Additionally, SYNAP was non-genotoxic and had low cytotoxicity against normal cells. SYNAP revealed encouraging anticancer activity, either alone or in combination with known chemotherapeutic agents, in colon cancer cells. Apart from its promising application in cancer therapy, SYNAP may provide a starting point for improved p53 activators.

Physically-triggered nanosystems based on two-dimensional materials for cancer theranostics.

There is an increasing demand to develop effective methods for treating malignant diseases to improve healthcare in our society. Stimuli-responsive nanosystems, which can respond to internal or external stimuli are promising in cancer therapy and diagnosis due to their functionality and versatility. As a newly emerging class of nanomaterials, two-dimensional (2D) nanomaterials have attracted huge interest in many different fields including biomedicine due to their unique physical and chemical properties. In the past decade, stimuli-responsive nanosystems based on 2D nanomaterials have been widely studied, showing promising applications in cancer therapy and diagnosis, including phototherapies, magnetic therapy, drug and gene delivery, and non-invasive imaging. Here, we will focus our attention on the state-of-the-art of physically-triggered nanosystems based on graphene and two-dimensional nanomaterials for cancer therapy and diagnosis. The physical triggers include light, temperature, magnetic and electric fields.

Fabrication of ultrasmall WS2 quantum dots-coated periodic mesoporous organosilica nanoparticles for intracellular drug delivery and synergistic chemo-photothermal therapy.

IntroductionThe consolidation of different therapies into a single nanoplatform has shown great promise for synergistic tumor treatment. In this study, a multifunctional platform by WS2 quantum dots (WQDs)-coated doxorubicin (DOX)-loaded periodic mesoporous organosilicas (PMOs-DOX@WQDs) nanoparticles were fabricated for the first time, and which exhibits good potential for synergistic chemo-photothermal therapy.Materials and methodsThe structure, light-mediated drug release behavior, photothermal effect, and synergistic therapeutic efficiency of PMOs-DOX@WQDs to HCT-116 colon cancer cells were investigated. The thioether-bridged PMOs exhibit a high DOX loading capacity of 66.7 μg mg−1. The gating of the PMOs not only improve the drug loading capacity but also introduce the dual-stimuli-responsive performance. Furthermore, the as-synthesized PMOs-DOX@WQDs nanoparticles can efficiently generate heat to the hyperthermia temperature with near infrared laser irradiation.ResultsIt was confirmed that PMOs-DOX@WQDs exhibit remarkable photothermal effect and light-triggered faster release of DOX. More importantly, it was reasonable to attribute the efficient anti-tumor efficiency of PMOs-DOX@WQDs.ConclusionThe in vitro experimental results confirm that the fabricated nanocarrier exhibits a significant synergistic effect, resulting in a higher efficacy to kill cancer cells. Therefore, the WQD-coated PMOs present promising applications in cancer therapy.

Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents.

Cell membranes with their selective permeability play important functions in the tight control of molecular exchanges between the cytosol and the extracellular environment as the intracellular membranes do within the internal compartments. For this reason the plasma membranes often represent a challenging obstacle to the intracellular delivery of many anti-cancer molecules. The active transport of drugs through such barrier often requires specific carriers able to cross the lipid bilayer. Cell penetrating peptides (CPPs) are generally 5–30 amino acids long which, for their ability to cross cell membranes, are widely used to deliver proteins, plasmid DNA, RNA, oligonucleotides, liposomes and anti-cancer drugs inside the cells. In this review, we describe the several types of CPPs, the chemical modifications to improve their cellular uptake, the different mechanisms to cross cell membranes and their biological properties upon conjugation with specific molecules. Special emphasis has been given to those with promising application in cancer therapy.

Comparison of Cold Atmospheric Plasma Devices’ Efficacy on Osteosarcoma and Fibroblastic In Vitro Cell Models

Cold atmospheric plasma (CAP) attenuates tumor cell proliferation and induces apoptosis in various cell lines. While exerting marginal effects on non-neoplastic cells this unfolds promising applications in cancer therapy. The aim of the study was to analyse the effects of different CAP sources and application times on osteosarcoma (OS) cells and non-malignant fibroblast cell proliferation. U2-OS and 3-T-3 fibroblasts were treated with three different approved medical devices. Carrier gas-treated cells served as controls. Cell proliferation was determined by viable cell count at different time points after treatment. Control exposed U2-OS and 3-T-3 cells exhibited characteristic cell growth. CAP application of U2-OS and 3-T-3 cells attenuated proliferation rates up to 98%. Attenuation rates varied between cell lines, plasma sources and application times. CAP treatment attenuates cell proliferation of OS cancer cells and fibroblasts in a treatment time-dependent manner, whereby U2-OS cells appeared more sensitive to CAP treatment as 3T3 fibroblasts after 10 sec of treatment.

Mesoporous Silica Nanoparticles Capped with Graphene Quantum Dots for Potential Chemo-Photothermal Synergistic Cancer Therapy.

In this study, mesoporous silica nanoparticles (MSNs) have been successfully capped with graphene quantum dots (GQDs) to form multifunctional GQD-MSNs with the potential for synergistic chemo-photothermal therapy. The structure, drug-release behavior, photothermal effect, and synergistic therapeutic efficiency of GQD-MSNs to 4T1 breast cancer cells were investigated. The results showed that GQD-MSNs were monodisperse and had a particle size of 50-60 nm. Using doxorubicin hydrochloride (DOX) as a model drug, the DOX-loaded GQD-MSNs (DOX-GQD-MSNs) not only exhibited pH- and temperature-responsive drug-release behavior, but using near-infrared irradiation, they efficiently generated heat to kill cancer cells. Furthermore, GQD-MSNs were biocompatible and were internalized by 4T1 cells. Compared with chemotherapy and photothermal therapy alone, DOX-GQD-MSNs were much more effective in killing the 4T1 cells owing to a synergistic chemo-photothermal effect. Therefore, GQD-MSNs may have promising applications in cancer therapy.