Temperature-responsive and biocompatible nanocarriers based on clay nanotubes for controlled anti-cancer drug release (original) (raw)

Enzyme-activated intracellular drug delivery with tubule clay nanoformulation

Scientific reports, 2015

Fabrication of stimuli-triggered drug delivery vehicle s is an important milestone in treating cancer. Here we demonstrate the selective anticancer drug delivery into human cells with biocompatible 50-nm diameter halloysite nanotube carriers. Physically-adsorbed dextrin end stoppers secure the intercellular release of brilliant green. Drug-loaded nanotubes penetrate through the cellular membranes and their uptake efficiency depends on the cells growth rate. Intercellular glycosyl hydrolases-mediated decomposition of the dextrin tube-end stoppers triggers the release of the lumen-loaded brilliant green, which allowed for preferable elimination of human lung carcinoma cells (А549) as compared with hepatoma cells (Hep3b). The enzyme-activated intracellular delivery of brilliant green using dextrin-coated halloysite nanotubes is a promising platform for anticancer treatment.

Halloysite clay nanotubes for life sciences applications: From drug encapsulation to bioscaffold

Advances in colloid and interface science, 2018

Natural forming clay halloysite is an emerging nanomaterial carrier for sustained drug delivery. These 50 nm diameter aluminosilicate tubes, with inner - alumina and outer - silica surface layers, can be loaded with 10-30 wt% of drug molecules, DNA and enzymes. The opposite charge of the inner and outer halloysite surface allow for selective drug adsorption inside or outside the clay nanotubes. The drug loaded halloysite enhanced the zeta potential of minus 50-60 mV allowing for stable aqueous nanocolloids. Halloysite nanoformulations provide an extended 10-20 h release profile, and may be functionalized (e.g., clogging tubes' end with polymers extending release time to 1-2 weeks or allowing for triggered release), which renders these clay nanostructures as promising controlled delivery systems. Recent studies demonstrate the potential of abundantly available halloysite clay nanotubes for life science applications, from drug delivery via oral or topical administration, to tissue...

Bi-Functionalized Clay Nanotubes for Anti-Cancer Therapy

Applied Sciences

Systemic toxicity is an undesired consequence of the majority of chemotherapeutic drugs. Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. Halloysite clay nanotubes (HNTs) have shown potential as a drug delivery vehicle, and its surface can be modified and tailored as a targeted drug delivery system. In this short report, we modified the HNT surface by covalently bonding folic acid (FA) and fluorescein isothiocyanate (FITC). The modification of HNTs with folic acid imparts the potential to target tumor cells selectively. The addition of FITC offers a method for quantifying the effectiveness of the FA tagged HNTs ability to target tumor cells. We documented cell uptake of our bi-functionalized HNT (bHNT) through phase contrast and epi-fluorescent microscopy. bHNTs showed no signs of cytotoxicity up to a concentration of 150 µg/mL. The increase in cell death with increased bHNT concentration may be due to induced cytotoxicity resulting from intracellular bHNT accumulation that disrupts cellular function leading to cell death. With HNTs recognized as having the ability to serve as both a nanocontainer and nanocarrier, we envision our construct as a potential modular platform for potential use in cancer therapeutics. The HNT interior can be loaded with a variety of anti-cancer drugs (or other chemotherapeutics) and serve as a "death cargo" designed to kill cancer cells while providing feedback imaging data on drug efficacy. The surface of the HNT can be modified with gold or silver nanoparticles and used in photothermal therapy by converting light to heat inside tumors. Our HNT-based drug delivery system has the potential to provide localized and targeted therapies that limit or reduce side effects, reduce patient costs and length of hospital stays, and improve quality of life. However, further research is needed to validate the potential of this new chemotherapeutic drug delivery system.

Halloysite clay nanotubes: characterization, biocompatibility and use as drug carriers

2008

Halloysite is aluminosilicate clay with hollow tubular structure. Biocompatibility study is important for its potential application in controlled drug delivery. Halloysite nanotubes were added to different cell cultures for toxicity tests. Its fluorescence functionalisation by APTES and with fluorescently-labeled polyelectrolyte layers allowed following halloysite uptake by the cells with Confocal Laser Scanning Microscopy (CLSM). Quantitative Trypan blue and MTT measurements performed with two neoplastic cell lines model systems as function of the nanotubes concentration and incubation time indicate that halloysite exhibits a high level of biocompatibility and very low cytotoxicity, rendering it a good candidate for household materials and medicine. A combination of Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM) and Scanning Force microscopy (SFM) imaging techniques have been employed to elucidate the structure of halloysite nanotubes.

Chitosan-Coated Halloysite Nanotubes As Vehicle for Controlled Drug Delivery to MCF-7 Cancer Cells In Vitro

Materials

The aim of the work is to improve the release properties of curcumin onto human breast cancer cell lines using coated halloysite nanotubes (HNTs) with chitosan as a polycation. A loading efficiency of 70.2% (w/w) was attained for loading 4.9 mg of the drug into 0.204 g bed volume of HNTs using the vacuum suction method. Results acquired from Brunauer-Emmett-Teller (BET), Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron spectroscopy (SEM), zeta potential, and thermogravimetric analysis (TGA) indicated the presence of the drug and the biopolymer in and around the nanotubes. The release properties of drug-loaded HNTs (DLHNTs) and chitosan-coated drug-loaded HNTs (DLHNTs-CH) were evaluated. The release percentages of DLHNTs and DLHNTs-CH after 6 h were 50.7 and 37%, respectively. Based on the correlation coefficients obtained by fitting the release nature of curcumin from the two samples, the Korsmeyer-Peppas model was found to be...

Loading and release of cancer chemotherapy drugs utilizing simultaneous temperature and pH-responsive nanohybrid

BMC Pharmacology and Toxicology, 2021

Background Recently, the development of nanocarriers and the improvement of their biochemical properties have became of great importance. Single-walled carbon nanotubes (SWCNT) have many applications in drug delivery systems (DDS) as a common carbon-based structure. In the current work, the penetration, co-loading, and co-release of Doxorubicin (DOX) and Paclitaxel (PAX), as two cancer chemotherapy agents, were investigated using a novel modified copolymer with functionalized SWCNT. Results This study proposes a dual-responsive smart carrier that is sensitive to pH and temperature. The carrier consists of functionalized SWNT and Dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) grafting on SWCNT. This suggested carrier was investigated by utilizing molecular simulations. Interaction energies between DOX, PAX, and carrier as well as the affinity of drugs to the nanocarrier were studied. The energy analysis of drug release and adsorption presented that DOX and PAX delivery using this ...

Clay nanotube encapsulation for functional biocomposites

Advances in colloid and interface science, 2014

Natural halloysite clay nanotubes with 50 nm outer- and 15 nm inner- diameters are described as miniature vehicles for sustained release of drugs and proteins. The release time may be adjusted from 10 to 200 h with the tube surface polymeric coating. An explanation of sustained release through locking electrical potential at the nanotube ends is suggested. These biocompatible ceramic tubes may be also used for architectural construction of nanoshells on microbes through alternation with polycations to enhance the intrinsic properties of biological cells. Halloysite nanotubes (pristine or drug-loaded) are well mixable with polar and low-polar polymers allowing for functional biocomposites with enhanced mechanical strength, adhesivity and slow release of drugs or other chemical agents. Halloysite is nontoxic abundantly available from natural deposit material which does not require exfoliation or other complicated energy consuming processing.

Spherical and tubule nanocarriers for sustained drug release

Current opinion in pharmacology, 2014

We discuss new trends in Layer-by-Layer (LbL) encapsulation of spherical and tubular cores of 50-150 nm diameter and loaded with drugs. This core size decrease (from few micrometers to a hundred of nanometers) for LbL encapsulation required development of sonication assistant non-washing technique and shell PEGylation to reach high colloidal stability of drug nanocarriers at 2-3mg/mL concentration in isotonic buffers and serum. For 120-170 nm spherical LbL nanocapsules of low soluble anticancer drugs, polyelectrolyte shell thickness controls drug dissolution. As for nanotube carriers, we concentrated on natural halloysite clay nanotubes as cores for LbL encapsulation that allows high drug loading and sustains its release over tens and hundreds hours. Further drug release prolongation was reached with formation of the tube-end stoppers.

Halloysite Nanotubes, a Multifunctional Nanovehicle for Anticancer Drug Delivery

Chinese Journal of Chemistry, 2012

Targeted drug delivery systems have attracted a great deal of interest by virtue of their potential use in chemotherapy. In this study, multicomponent halloysite nanotubes (HNTs) have been evaluated as a platform to assist and direct the delivery of anticancer drug doxorubicin (DOX) into cancer cells. Folic acid (FA) and magnetite nanoparticles were successfully grafted onto HNTs via amide reaction whereas the drug has been introduced by capitalizing electrostatic interaction between cationic drug and anionic exterior of HNTs, which eventually leads to pH responsive release. The resultant DOX loaded FA-Fe 3 O 4 @HNTs were well characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and XRD. The clinical efficacy of the system was validated by confocal microscopy and cell cytotoxicity assay (MTT assay). MTT assay results revealed a high biocompatibility up to a concentration of 200 μg/mL of HNTs, while, DOX loaded FA-Fe 3 O 4 @HNTs were markedly cytotoxic to HeLa cells. This multifunctional nanovehicle has a great potential for cancer diagnosis and therapy, and could further advance the clinical use of nanomedicine.

Nano-Clays for Cancer Therapy: State-of-the Art and Future Perspectives

Journal of Personalized Medicine

To date, cancer continues to be one of the deadliest diseases. Current therapies are often ineffective, leading to the urgency to develop new therapeutic strategies to improve treatments. Conventional chemotherapeutics are characterized by a reduced therapeutic efficacy, as well as them being responsible for important undesirable side effects linked to their non-specific toxicity. In this context, natural nanomaterials such as clayey mineral nanostructures of various shapes (flat, tubular, spherical and fibrous) with adjustable physico-chemical and morphological characteristics are emerging as systems with extraordinary potential for the delivery of different therapeutic agents to tumor sites. Thanks to their submicron size, high specific surface area, high adsorption capacity, chemical inertia and multilayer organization of 0.7 to 1 nm-thick sheets, they have aroused considerable interest among the scientific community as nano systems that are highly biocompatible in cancer therapy...