Anticancer Drug Carrier Research Articles

Surface adsorption of Crizotinib on carbon and boron nitride nanotubes as Anti-Cancer drug Carriers: COSMO-RS and DFT molecular insights

In this study, the adsorption mechanisms and interactions between the anticancer molecule Crizotinib (CZT) on the surfaces of carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs) are investigated. The investigations are carried out using the density functional theory (DFT) and the conductor-like screening model for real solvents (COSMO-RS). The quantum molecular descriptors (QMD) are also computed to explain the drug-carrier interaction mechanism and energy of adsorption. The negative adsorption energies of the complex drug-CNT indicate that adsorption is exothermic. The electrophilicity index of the drug-CNT system is five times greater than that of the drug-BNNT, demonstrating the higher stability of the CNTs with respect to BNNT. Moreover, a stronger interaction is observed for CZT-CNT, using the COSMO-RS method. A solvation study in water also reveals that the CZT-CNT complex is more soluble than CZT-BNNT. Finally, a quantum theory of atoms in molecules (QTAIM) analysis is also applied to investigate the nature of the intermolecular interactions. Based on the obtained results, it can be concluded that CNTs are more stable and better carriers than BNNTs when applied for CZT drug delivery in biological media.

Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs

Small interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.

Multi-stimuli-responsive performance and morphological changes of radical-functionalized self-assembled micellar nanoaggregates and their multi-triggered drug release

Stimuli-responsive self-assembled nanostructures are of great interest as smart materials in different industries, but there are limitations to obtain such materials in radical-functionalized amphiphilic random copolymers owing to structural illness. Herein, a series of novel radical-functionalized poly(N-isopropyl methacrylamide- co -acrylic acid)s (RF-p(NIPMAM-co-AA)s) amphiphilic random copolymers were synthesized and their self-assembled nanostructures were studied by electron spin resonance (ESR) with other analytical techniques. ESR spectroscopy and TEM revealed the formation of smart supramolecular nanoaggregates (SNAs), their multi-stimuli-responsiveness and morphological transitions in different external parameters ( e.g . pH, temperature, reductant, polarity and viscosity), hence, ESR spectroscopy provides the dynamics of inter and/or intra-molecular interactions of polymer chains dependent on nanomaterial’s environments. At a more acidic medium, the colloidal nanoparticles were shown to disassemble due to the disproportionation of nitroxide radicals. The particles’ morphology was observed to be a lower critical solution temperature (LCST) type, where multi-micelle aggregates were formed upon increasing the temperature. The kinetically controlled redox-triggered disassembly was noticed upon the addition of different molar equivalents of vitamin C (VC) as a reducing agent. Interestingly, the morphological transitions were observed on changing the polarity of the medium, whereas THF and 1-octanol were used as nonpolar solvents. These observations are helpful to yield insight into the structure-property relationship of colloidal supramolecular nanosystems and could be used to design similar spontaneous and controlled self-assembled nanostructures by regulating the microenvironments. The biocompatibility of the assemblies was investigated by hemolysis assay. As a proof-of-concept demonstration, we utilized the nanoaggregates as an anticancer drug carrier in multi-triggered release systems. • Multi-stimuli-responsive performance of stable radical-functionalized nanoparticles has been reported. • Dynamical and structural information has been investigated by electron spin resonance spectroscopy. • Proof-of-concept demonstration was proved their multi-triggered application in anticancer drug delivery. • This design promotes a robust and simple synthesis of spontaneous and controlled stimuli-responsive nanosystems.

Atomistic Study of Several Peptides Covering Single‐walled Carbon Nanotube by Noncovalent Adsorption

Single-walled Carbon Nanotubes (SWNTs) have shown outstanding physicochemical, mechanical, electronic, and optical properties that enable a broad range of biomedical applications, including drug delivery (carrier for anti-cancer drugs), imaging (carrier for contrast agents), tissue engineering (bone, nerve, and cardiac), gene delivery, and biosensors. However, their carbon hexagonal-lattice nanostructure causes a sizeable surface-to-volume ratio with a potent van der Waals surface that leads to limiting characteristics for bioapplications (e.g., low solubility, agglomeration, and potential toxicity). In this perspective, the biomolecule-adsorption strategy that exhibits advantageous characteristics over covalent functionalization could not only help overcome these SWNT limitations but also preserve its pristine sp2 hybridization wall by noncovalently binding amphiphilic peptides. The objective of this computational study is to investigate the fundamental interactions and properties of ten different segments (lower than 40 amino acids) on (16,0) SWNT system using Molecular Dynamics (MD) simulations that are essential and effective factors on SWNT applications, particularly for drug delivery. This proposed coverage of natural-sequence peptides can potentially be easier recognized by biological processes as well as increase dispersibility and decrease toxicity of SWNT.

Facile solvothermal synthesis of monodisperse superparamagnetic mesoporous Fe3O4 nanospheres for pH-responsive controlled drug delivery

In the present work, monodisperse Fe3O4 nanospheres with typical mesoporous structures and superparamagnetic characteristics were synthesized through a simple solvothermal approach. Various characterization experiments including SEM, TEM, XRD, XPS, BET and SQUID were performed to investigate in detail the morphology, microstructure, composition and physicochemical properties of the prepared Fe3O4 nanospheres. It was found that the average diameter of Fe3O4 nanospheres was determined to be about 207.3 nm with a relatively narrow size distribution. The analysis of nitrogen adsorption/desorption isotherms indicated that Fe3O4 nanospheres represented typical mesoporous structures having a surface area of 20.68 m2/g. The magnetic property measurements demonstrated that the synthesized nanospheres behaved as superparamagnetic with a high saturation magnetization of 97.5 emu/g. Most importantly, the mesoporous Fe3O4 nanospheres could be utilized as a potential anti-cancer drug carrier for doxorubicin hydrochloride (DOX). The drug loading capacity and in vitro drug release behavior of DOX in phosphate buffered solutions under different pH values (4.0, 5.5 and 7.4) were examined. The results showed that the developed drug delivery system based on mesoporous Fe3O4 nanospheres exhibited a high drug loading capacity and a controlled drug release behavior.

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

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.

Silver Nanoparticles as Carriers of Anticancer Drugs for Efficient Target Treatment of Cancer Cells.

Since the last decade, nanotechnology has evolved rapidly and has been applied in several areas, such as medicine, pharmaceutical, microelectronics, aerospace, food industries, among others. The use of nanoparticles as drug carriers has been explored and presents several advantages, such as controlled and targeted release of loaded or coupled drugs, and the improvement of the drug’s bioavailability, in addition to others. However, they also have some limitations, related to their in vivo toxicity, which affects all organs including the healthy ones, and overall improvement in the disease treatment, which can be unnoticeable or minimal. Silver nanoparticles have been increasingly investigated due to their peculiar physical, chemical, and optical properties, which allows them to cover several applications, namely in the transport of drugs to a specific target in the body. Given the limitations of conventional cancer chemotherapy, which include low bioavailability and the consequent use of high doses that cause adverse effects, strategies that overcome these difficulties are extremely important. This review embraces an overview and presentation about silver nanoparticles used as anticancer drug carrier systems and focuses a discussion on the state of the art of silver nanoparticles exploited for transport of anticancer drugs and their influence on antitumor effects.

A narrative review of tumor-associated macrophages in lung cancer: regulation of macrophage polarization and therapeutic implications.

Lung cancer is the deadliest malignancy worldwide. An inflammatory microenvironment is a key factor contributing to lung tumor progression. Tumor-Associated Macrophages (TAMs) are prominent components of the cancer immune microenvironment with diverse supportive and inhibitory effects on growth, progression, and metastasis of lung tumors. Two main macrophage phenotypes with different functions have been identified. They include inflammatory or classically activated (M1) and anti-inflammatory or alternatively activated (M2) macrophages. The contrasting functions of TAMs in relation to lung neoplasm progression stem from the presence of TAMs with varying tumor-promoting or anti-tumor activities. This wide spectrum of functions is governed by a network of cytokines and chemokines, cell-cell interactions, and signaling pathways. TAMs are promising therapeutic targets for non-small cell lung cancer (NSCLC) treatment. There are several strategies for TAM targeting and utilizing them for therapeutic purposes including limiting monocyte recruitment and localization through various pathways such as CCL2-CCR2, CSF1-CSF1R, and CXCL12-CXCR4, targeting the activation of TAMs, genetic and epigenetic reprogramming of TAMs to antitumor phenotype, and utilizing TAMs as the carrier for anti-cancer drugs. In this review, we will outline the role of macrophages in the lung cancer initiation and progression, pathways regulating their function in lung cancer microenvironment as well as the role of these immune cells in the development of future therapeutic strategies.

Graphene Oxide as a Carrier for Drug Delivery of Methotrexate

Nanomaterials, including carbon-based nanoparticles, have been applied as carriers for anticancer drugs. This short communication reported the synthesis, cytotoxicity, and drug delivery of methotrexate using graphene oxide (GO) as a carrier. GO was synthesized following Hummer's method. It was characterized using X-ray diffraction (XRD), transmission electron microscope (TEM), and scanning electron microscope (SEM). Data analysis confirms the synthesis of GO with high crystallinity and lamellae morphology. GO showed a high cytocompatibility toward the human EA.hy926 endothelial cells. GO has been used as a carrier for the anticancer drug; methotrexate. The drug delivery was tested for hepatocellular carcinoma cells (HepG2 cells), human embryonic kidney cells (HEK293A cells), and porcine skin fibroblasts (PEF).

Ion exchange column technique as a novel method for evaluating the release of docetaxel from different lipid nanoparticles.

Lipid nanoparticles with their unique characters showed many advantages as carriers for anticancer drugs. To compare between these nanoparticles as carriers for anticancer drugs, it was important to evaluate and characterize their drug retention and release properties. In this study, ion exchange column is used as a new evaluation technique. Solid lipid nanoparticles (SLN), nanostructured lipid carrier (NLC), and cubic nanoparticles were prepared using the homogenization technique. Characterization of these nanoparticles was carried out by measuring particle size, zeta potential, and entrapment efficiency. The ion exchange column was used to evaluate docetaxel release from the different nanoparticles as donors to acceptor liposomes that mimic the cell membranes. Both populations were mixed and at different time points, separated using the columns. The amounts of docetaxel in the eluted nanoparticles and retained liposomes were calculated. The particle size of all donors was in the nanometer range with almost neutral zeta potential. The particle size of the acceptor liposomes was 135nm with a high negative zeta potential -55mV. Ion exchange columns showed excellent retention of the negative acceptor liposomes while less than 1% of the different donors were retained on the columns. Cubic nanoparticles showed the highest entrapment efficiency (95%) and the slowest drug transfer in comparison with SLN and NLC. In conclusion, the ion exchange column technique can be applied successfully to evaluate the release of docetaxel from the different lipid nanoparticles to acceptor liposomes. Cubic nanoparticles showed advantageous docetaxel incorporation and transfer over SLN and NLC.

Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment.

Since more than 40 years liposomes have being extensively studied for their potential as carriers of anticancer drugs. The basic principle behind their use for cancer treatment consists on the idea that they can take advantage of the leaky vasculature and poor lymphatic drainage present at the tumor tissue, passively accumulating in this region. Aiming to further improve their efficacy, different strategies have been employed such as PEGlation, which enables longer circulation times, or the attachment of ligands to liposomal surface for active targeting of cancer cells. A great challenge for drug delivery to cancer treatment now, is the possibility to trigger release from nanosystems at the tumor site, providing efficacious levels of drug in the tumor. Different strategies have been proposed to exploit the outer and inner tumor environment for triggering drug release from liposomes and are the focus of this review.

Preparation, characterization, and cytotoxicity evaluation of self-assembled nanoparticles of diosgenin-cytarabine conjugate

Diosgenin (DG) isolated from yam roots revealed various bioactivities and applications as drug carrier. In the present study, a conjugate of DG with cytarabine (Ara-C) was used to prepare the self-assembled nanoparticles (NPs) of DG-Ara-C by a nanoprecipitation method. Dynamic light scattering (DLS) as well as transmission electron microscopy (TEM) were employed to analyze the size and the morphology of NPs, respectively. The stability and absorption of DG-Ara-C NPs were measured. Additionally, the cytotoxicity of the NPs was determined via MTT assay. The results indicated that the average particle size of DG-Ara-C NPs was around 190 nm with a narrow size distribution (PDI = 0.1). TEM showed that DG-Ara-C NPs had a spherical morphology. Compared to free DG or Ara-C, the self-assembled DG-Ara-C NPs exhibited a better anti-tumor activity against solid tumor cells as well as leukemia cells. In conclusion, DG possesses dual role in the self-assembled NPs of DG-Ara-C conjugate, being as a promising anticancer drug and drug carrier.

Nanocellulose as a Vehicle for Drug Delivery and Efficiency of Anticancer Activity: A Short-Review

With the high demand of using nanotechnology, nanocellulose has become popular for different biomedical and anticancer applications. Cellulose, a nature gifted material and the most abundant organic polymer on earth, is systematically reviewed. Details of the mechanical and chemical structure of nanocellulose are explained, starting with preparation methods along with physiochemical properties and pH gradient to incorporate innovative polymeric drug delivery vehicles in anticancer applications. A myriad of research fields has introduced nanocellulose as an intriguing candidate for anticancer drug excipient and carrier in modern cancer therapy. Albeit, innovative nanocellulose-based drug carrier systems will be complicated for their commercial use in pharmacies. Of this, it is required to understand the preparation, properties, and potential drug conjugation of nanocellulose to improve its interactions with human tissues.

A two-fold interpenetration pillar-layered metal-organic frameworks based on BODIPY for chemo-photodynamic therapy

The combination of chemotherapy and photodynamic therapy has been proved to be a promising therapy for drug-resistant cancers. In this study, we report, for the first time, a novel two-fold interpenetration pillar-layered metal-organic frameworks (MOFs) material, using BODIPY-derivate bipyridine as linker and Photosensitizer (PS), named BBP-MOFs, was successfully synthesized to serve as a drug carrier and Photodynamic agent simultaneously. The BBP-MOFs could generate singlet oxygen (1O2) to perform PDT under 660 nm light irradiation, in the meantime, the anticancer drugs doxorubicin (DOX) could be loaded for chemotherapy. The results showed that BBP-MOFs exhibited a high drug loading content of 49.7% a controlled drug release and ideal biocompatibility. This DOX loaded BBP-MOFs was readily taken up by HeLa cells, and high levels of 1O2 were generated under light irradiation. This work provided strong evidence for BBP-MOFs as a promising new anticancer drug carrier and PDT candidate, the PDT and chemotherapy combined synergistic therapy revealed high therapeutic efficacy for cancer cells.

MD and DFT calculations on the structural variations of amino-cyclodextrin as a pH-sensitive carrier for smart carriage and release of Doxorubicin

Cyclodextrins have been widely employed as nanocarriers due to their unique structure and proper controlled drug delivery as well as nontoxicity, water solubility, and proper capacity to carry hydrophobic drugs. In addition, pH-sensitized compounds have found particular importance in the field of anticancer drug delivery. In this study, the structure of amino-β-cyclodextrin was theoretically explored as a pH-sensitive and smart carrier for Doxorubicin anticancer drug. To this end, quantum chemical calculation methods and molecular dynamics (MD) simulations were applied on amino-β-cyclodextrin to assess its ability to carry Doxorubicin anticancer drug. Quantum chemistry results indicated a deformation in the nanocarrier during protonation. Moreover, interaction energy and quantum molecular describers confirm the drug storage under non-protonated conditions and its release under protonation conditions. Hydrogen bonding, carrier-drug energy, and center of mass (COM) distances (obtained from MD simulation) also suggest drug carrying and releasing under non-protonated and protonated conditions, respectively.

5FU encapsulated polyglycerol sebacate nanoparticles as anti-cancer drug carriers.

The majority of anti-cancer drugs fail to reach clinical trials due to their low water solubility. A biocompatible drug delivery system that encapsulates and efficiently delivers hydrophobic drugs to the target site is the need of the hour. This study addresses the issue by focusing on a polymeric polyglycerol sebacate (PGS) nanoparticles loaded with 5-fluorouracil (5FU), a primary line chemotherapy drug for many types of cancers. The generated nanoparticle (PGS-NP) was biocompatible and had minimal cytotoxicity against the MDA-MB-231 and A549 cell lines, even at a high concentration of 100 μg mL−1. The cell viability post treatment with PGS nanoparticles encapsulated with 5FU (PGS-5FU) decreased to as low as around 40% whereas, in the case of treatment with 5FU, the viability percentage increased. The nanoparticles also showed controlled drug release when encapsulated with 5FU. This striking observation suggested that these nanoparticles can improve the efficacy of drug delivery to tumor sites. Apoptosis assay and caspase-3 activity quantification supported these data wherein PGS-5FU treatment showed almost three times caspase-3 activity as compared to control cells. Additionally, throughout all the experiments, MDA-MB-231 cells were more sensitive to PGS-5FU than A549 cells, indicating that these nanoparticles are ideal for breast cancer treatment. In summary, 5FU encapsulated PGS nanoparticles are a potential drug carrier to deliver 5FU efficiently to cancer cells.

Ultra-thin patchy polymer-coated graphene oxide as a novel anticancer drug carrier

PISA generated polymer pimples on single graphene oxide sheets maintain colloidal stability for the adsorption and release of DOX.

Surface adsorption of nitrosourea on pristine and doped (Al, Ga and In) boron nitride nanosheets as anticancer drug carriers: the DFT and COSMO insights.

To minimize the side effects of chemotherapeutic drugs and enhance the effectiveness of cancer treatment, it is necessary to find a suitable drug delivery carrier for anticancer drugs. Recently nanomaterials are extensively being studied as drug vehicles and transport drugs in tumor cells. Using DFT calculations, the adsorption behavior with electronic sensitivity and reactivity of pristine and doped (Al, Ga and In)-BNNS towards the nitrosourea (NU) drug has been investigated in gas as well as water media. Our calculations showed that the NU drug is physically adsorbed on the pristine BNNS with −0.49 and −0.26 eV by transferring little amount of charge of about 0.033e and 0.046e in gas and water media in the most stable complex. But after replacing one of the central B atoms with an Al or Ga or In atom, the sensitivity of the doped BNNS remarkably enhances towards the NU drug molecules. The NU drug prefers to be chemically adsorbed on the BN(Al)NS, BN(Ga)NS and BN(In)NS by −1.28, −1.58 and −3.06 eV in the gas phase and −1.34, −1.23 and −3.65 eV in water media in the most stable complexes respectively. The large destabilization of LUMO energies after the adsorption of the NU drug on the BN(Al)NS, BN(Ga)NS and BN(In)NS significantly reduces their Eg from 4.37 to 0.69, 4.37 to 1.04 and 4.33 to 0.66 eV in the S1 complex respectively. The reduction of Eg of doped BNNS by the NU drug greatly enhances the electrical conductivity which can be converted to an electrical signal. Therefore, this doped BNNS can be used as a fascinating electronic sensor for the detection of NU drug molecules. Furthermore the work function of the doped BNNS was largely affected by the NU drug adsorption about 47.3%, 39.3% and 40.4% in the gas phase and 41.3%, 36.6% and 31.6% in water media in the S1 complex of NU/BN(Al)NS, NU/BN(Ga)NS and NU/BN(In)NS respectively. Thus, the doped BNNS may be used as a Ф type sensor for NU drug molecules.

Magnetic hydroxyapatite nanomaterial–cyclodextrin tethered polymer hybrids as anticancer drug carriers

Osteosarcoma, the most common bone cancer, leads to a poor survival rate of patients. Drug targeting employing hydroxyapatite (HAp)-based nanocarriers represents a fascinating choice for non-invasive treatment of osteosarcoma.

Thermodynamic Studies on Calixarene Nanoparticles as a Carrier and Adsorbent of Mercaptopurine Anticancer Drug in Drug Delivery Using Experimental Methods

Calix [4] arene refers to a group of large cyclic compounds involving a sequence of phenols, which are obtained through the hydroxylation reaction process of phenol and aldehyde derivatives. Calixarenes have a rigid and three-dimensional structure. Nanoparticles can be used in drug delivery due to their ability to enter cells. The application of a carrier for drug delivery is very effective on improving their performance. In order to employ calixarene nanoparticles as the carriers of mercaptopurine drug, their ability and type of adsorption were examined on laboratory scale. In this study, by examining the temperature changes on the course of adsorption and by matching the data against Langmuir adsorption isotherm, Freundlich, and Dubin Radushkovich, the numbers of all thermodynamic constants of this process were calculated. The obtained adsorption capacities indicated that the elevation of the initial concentration leads to the enhanced adsorption capacity. Moreover, by considering the obtained thermodynamic constants, it was found that the adsorption process is exothermic, while the values of Gibbs free energy ∆G0 and the adsorption energy Ea showed that the adsorption process was spontaneous and chemical.