Thermosensitive polymer prodrug nanoparticles prepared by an all-aqueous nanoprecipitation process and application to combination therapy.

Despite their great versatility and ease of functionalization, most polymer-based nanocarriers intended for use in drug delivery often face serious limitations that can prevent their clinical translation, such as uncontrolled drug release and off-target toxicity, which mainly originate from the burst release phenomenon. In addition, residual solvents from the formulation process can induce toxicity, alter the physico-chemical and biological properties and can strongly impair further pharmaceutical development. To address these issues, we report polymer prodrug nanoparticles, which are prepared without organic solvents via an all-aqueous formulation process, and provide sustained drug release. This was achieved by the "drug-initiated" synthesis of well-defined copolymer prodrugs exhibiting a lower critical solution temperature (LCST) and based on the anticancer drug gemcitabine (Gem). After screening for different structural parameters, prodrugs based on amphiphilic diblock copolymers were formulated into stable nanoparticles by all-aqueous nanoprecipitation, with rather narrow particle size distribution and average diameters in the 50-80 nm range. They exhibited sustained Gem release in human serum and acetate buffer, rapid cellular uptake and significant cytotoxicity on A549 and Mia PaCa-2 cancer cells. We also demonstrated the versatility of this approach by formulating Gem-based polymer prodrug nanoparticles loaded with doxorubicin (Dox) for combination therapy. The dual-drug nanoparticles exhibited sustained release of Gem in human serum and acidic release of Dox under accelerated pathophysiological conditions. Importantly, they also induced a synergistic effect on triple-negative breast cancer line MDA-MB-231, which is a relevant cell line to this combination.

Upconversion Nanoparticles Intercalated in Large Polymer Micelles for Tumor Imaging and Chemo/Photothermal Therapy.

Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs.

Sequential Dual Coating with Thermosensitive Polymers for Advanced Fiber Optic Temperature Sensors.

We systematically designed dual polymer Fabry-Perrot interferometer (DPFPI) sensors, which were used to achieve highly sensitive temperature sensors. The designed and fabricated DPFPI has a dual polymer coating layer consisting of thermosensitive poly (methyl methacrylate) (PMMA) and polycarbonate (PC) polymers. Four different DPFPI sensors were developed, in which different coating optical path lengths and the resultant optical properties were generated by the Vernier effect, changing the sequence of the applied polymers and varying the concentration of the coating solutions. The experimental results confirmed that the PC_PMMA_S1 DPFPI sensor delivered a temperature sensitivity of 1238.7 pm °C-1, which was approximately 4.4- and 1.4-fold higher than that of the PMMA and PMMA_PC_S1-coated sensor, respectively. Thus, the results reveal that the coating sequence, the compact thickness of the dual polymer layers, and the resultant optical parameters are accountable for achieving sensors with high sensitivity. In the PC_ PMMA-coated sensor, the PMMA outer layer has comparatively better optical properties than the PC, which might produce synergistic effects that create a large wavelength shift with small temperature deviations. Therefore, it is considered that the extensive results with the PC_PMMA_S1 DPFPI sensor validate the efficacy, repeatability, reliability, quick reaction, feasibility, and precision of the temperature readings.

Enhanced tumor penetration for efficient chemotherapy by a magnetothermally sensitive micelle combined with magnetic targeting and magnetic hyperthermia.

The high accumulation and poor penetration of nanocarriers in tumor is a contradiction of nanomedicine, which reduces the efficacy of chemotherapy. Due to the positive effect of hyperthermia on in vivo drug diffusion, we designed a magnetothermally sensitive micelle (MTM) by integrating magnetic targeting (MT), magnetic hyperthermia (MH), and magnetothermally responsive drug release to facilitate simultaneous drug accumulation and penetration in tumor. Accordingly, we synthesized a cyanine7-modified thermosensitive polymer with phase transition at 42.3°C, and utilized it to prepare drug-loaded MTMs by encapsulating superparamagnetic MnFe2O4 nanoparticles and doxorubicin (DOX). The obtained DOX-MTM had not only high contents of DOX (9.1%) and MnFe2O4 (38.7%), but also some advantages such as superparamagnetism, high saturation magnetization, excellent magnetocaloric effect, and magnetothermal-dependent drug release. Therefore, DOX-MTM improved in vitro DOX cytotoxicity by enhancing DOX endocytosis under the assistance of MH. Furthermore, MT and MH enhanced in vivo DOX-MTM accumulation and DOX penetration in tumor, respectively, substantially inhibiting tumor growth (84%) with excellent biosafety. These results indicate the development of an optimized drug delivery system with MH and MH-dependent drug release, introducing a feasible strategy to enhance the application of nanomedicines in tumor chemotherapy.

Synthetic Thermo-Responsive Terpolymers as Tunable Scaffolds for Cell Culture Applications.

The use of tailored synthetic hydrogels for in vitro tissue culture and biomanufacturing provides the advantage of mimicking the cell microenvironment without issues of batch-to-batch variability. To that end, this work focused on the design, characterization, and preliminary evaluation of thermo-responsive, transparent synthetic terpolymers based on N-isopropylacrylamide, vinylphenylboronic acid, and polyethylene glycol for cell manufacturing and in vitro culture applications. Polymer physical properties were characterized by FT-IR, 1H-NMR, DLS, rheology, and thermal-gravimetric analysis. Tested combinations provided polymers with a lower critical solution temperature (LCST) between 30 and 45 °C. Terpolymer elastic/shear modulus varied between 0.3 and 19.1 kPa at 37 °C. Cellular characterization indicated low cell cytotoxicity on NIH-3T3. Experiments with the ovarian cancer model SKOV-3 and Jurkat T cells showed the terpolymers' capacity for cell encapsulation without interfering with staining or imaging protocols. In addition, cell growth and high levels of pluripotency demonstrated the capability of terpolymer to culture iPSCs. Characterization results confirmed a promising use of terpolymers as a tunable scaffold for cell culture applications.

Engineering Au Nanoclusters for Relay Luminescence Enhancement with Aggregation-Induced Emission.

The research of aggregation-induced emission (AIE) has been growing rapidly for the design of highly luminescent materials, as exemplified by the library of AIE-active materials (or AIEgens) fabricated and explored for diverse applications in different fields. Herein, we reported a relay luminescence enhancement of luminescent Au nanoclusters (Au NCs) through AIE. In addition, we demonstrated the emergence of reduced aggregation-caused luminescence by adjusting the temperature of the Au NC solution. The key to induce this effect is to attach a thermosensitive polymer poly(N-isopropylacrylamide) (PNIPAAm) on the surface of Au NCs, which will shrink at high temperature. More interestingly, the as-synthesized Au NCs-PNIPAAm can self-assemble into vesicles, resulting in an obvious decrease in the luminescence intensity in aqueous solution. The combination of relay luminescence enhancement (by AIE) and luminescence decrease (induced by thermosensitive polymers) will be beneficial to the understanding and manipulation of the optical properties of Au NCs, paving the way for their practical applications.

On Demand Sequential Release of (Sub)Micron Particles Controlled by Size and Temperature.

Polymeric devices capable of releasing submicron particles (subMP) on demand are highly desirable for controlled release systems, sensors, and smart surfaces. Here, a temperature-memory polymer sheet with a programmable smooth surface served as matrix to embed and release polystyrene subMP controlled by particle size and temperature. subMPs embedding at 80 °C can be released sequentially according to their size (diameter D of 200 nm, 500 nm, 1 µm) when heated. The differences in their embedding extent are determined by the various subMPs sizes and result in their distinct release temperatures. Microparticles of the same size (D ≈ 1 µm) incorporated in films at different programming temperatures Tp (50, 65, and 80 °C) lead to a sequential release based on the temperature-memory effect. The change of apparent height over the film surface is quantified using atomic force microscopy and the realization of sequential release is proven by confocal laser scanning microscopy. The demonstration and quantification of on demand subMP release are of technological impact for assembly, particle sorting, and release technologies in microtechnology, catalysis, and controlled release.

Simply Fabricated Inexpensive Dual-Polymer-Coated Fabry-Perot Interferometer-Based Temperature Sensors with High Sensitivity.

We designed simply fabricated, highly sensitive, and cost-effective dual-polymer-coated Fabry-Perot interferometer (DFPI)-based temperature sensors by employing thermosensitive polymers and non-thermosensitive polymers, as well as different two successive dip-coating techniques (stepwise dip coating and polymer mixture coating). Seven sensors were fabricated using different polymer combinations for performance optimization. The experiments demonstrated that the stepwise dip-coated dual thermosensitive polymer sensors exhibited the highest sensitivity (2142.5 pm °C-1 for poly(methyl methacrylate)-polycarbonate (PMMA_PC) and 785.5 pm °C-1 for poly(methyl methacrylate)- polystyrene (PMMA_PS)). Conversely, the polymer-mixture-coated sensors yielded low sensitivities (339.5 pm °C-1 for the poly(methyl methacrylate)-polycarbonate mixture (PMMA_PC mixture) and 233.5 pm °C-1 for the poly(methyl methacrylate)-polystyrene mixture (PMMA_PS mixture). Thus, the coating method, polymer selection, and thin air-bubble-free coating are crucial for high-sensitivity DFPI-based sensors. Furthermore, the DFPI-based sensors yielded stable readouts, based on three measurements. Our comprehensive results confirm the effectiveness, reproducibility, stability, fast response, feasibility, and accuracy of temperature measurements using the proposed sensors. The excellent performance and simplicity of our proposed sensors are promising for biomedical, biochemical, and physical applications.

Preparation of thermosensitive PNIPAm-based copolymer coated cytodex 3 microcarriers for efficient nonenzymatic cell harvesting during 3D culturing.

Enzymatic detachment of cells might damage important features and functions of cells and could affect subsequent cell-based applications. Therefore, nonenzymatic cell detachment using thermosensitive polymer matrix is necessary for maintaining cell quality after harvesting. In this study, we prepared thermosensitive PNIPAm-co-AAc-b-PS and PNIPAm-co-AAm-b-PS copolymers and low critical solution temperature (LCST) was tuned near to body temperature. Then, spin coated polymer films were prepared for cell adhesion and thermal-induced cell detachment. The alpha-step analysis and scanning electron microscope image of the films suggested that the thickness of the films depends on the molecular weight and concentration which ranged from 206 to 1330 nm for PNIPAm-co-AAc-b-PS and 97.5-497 nm for PNIPAm-co-AAm-b-PS. The contact angles of the films verified that the polymer surface was moderately hydrophilic at 37°C. Importantly, RAW264.7 cells were convincingly proliferated on the films to a confluent of >80% within 48 h and abled to detach by reducing the temperature. However, relatively more cells were grown on PNIPAm-co-AAm-b-PS (5%w/v) films and thermal-induced cell detachment was more abundant in this formulation. As a result, PNIPAm-co-AAm-b-PS (5%w/v) was further used to coat commercial cytodex 3 microcarriers for 3D cell culturing and interestingly enhanced cell detachment with preserved potential of recovery was observed at a temperature of below LCST. Thus, surface modification of microcarriers with thermosensitive PNIPAm-co-AAm-b-PS could be vital strategy for nonenzymatic cell detachment and to achieve adequate number of cells with maximum cell viability and functionality.

Thermosensitive and Conductive Hybrid Polymer for Real-Time Monitoring of Spheroid Growth and Drug Responses.

Three-dimensional (3D) cell culture based on polymer scaffold provides a promising tool to mimic a physiological microenvironment for drug testing; however, the next-generation cell activity monitoring technology for 3D cell culture is still challenging. Conventionally, drug efficacy evaluation and cell growth heavily rely on cell staining assays, using optical devices or flow cytometry. Here, we report a dual-function polymer scaffold (DFPS) composed of thermosensitive, silver flake- and gold nanoparticle-decorated polymers, enabling conductance change upon cell proliferation or death for in situ cell activity monitoring and drug screening. The cell activity can be quantitatively monitored via measuring the conductance change induced by polymeric network swelling or shrinkage. This novel dual-function system (1) provides a 3D microenvironment to enable the formation and growth of tumor spheroid in vitro and streamlines the harvesting of tumor spheroids through the thermosensitive scaffold and (2) offers a simple and direct quantitative method to monitor 3D cell culture in situ for drug responses. As a proof of concept, we demonstrated that a breast cancer stem cell line MDA-MB-436 was able to form cell spheroids in the scaffold, and the conductance change of the sensor exhibited a linear relationship with cell concentration. To examine its potential in drug screening, cancer spheroids in the cell sensor were treated with paclitaxel (PTX) and docetaxel (DTX), and predicted quantitative evaluation of the cytotoxic effect of drugs was established. Our results indicated that this cell sensing system may hold promising potential in expanding into an array device for high-throughput drug screening.

Synthesis, Phase-Transition Behaviour, and Oil Adsorption Performance of Porous Poly(oligo(ethylene glycol) Alkyl Ether Acrylate) Gels.

To probe the effects of pendant side-chain structures on the properties of porous thermoresponsive polymer gels, oligo(ethylene glycol) alkyl ether acrylates were polymerised in an aqueous medium under radical-mediated phase-separation conditions. The monomer structures varied according to the lengths and termini of their ethylene glycol side chains. The porous poly(oligo(ethylene glycol) alkyl ether acrylate) (POEGA) gels exhibited variable lower critical solution temperatures (LCSTs) but similar and rapid swelling-deswelling behaviours. Although the LCST of the poly(tri(ethylene glycol) monomethyl ether acrylate) (PTEGA) gel decreased with increasing aqueous NaCl or CaCl2 concentration, PTEGA showed excellent thermosensitivity in highly concentrated salt solutions, recommending its application in saline environments. Examination of PTEGA adsorption performance in an oil-water emulsion showed that n-tridecane adsorption increased with temperature. Although n-tridecane was effectively adsorbed at 70 °C, its release from the fully adsorbed PTEGA gel was difficult despite a temperature reduction from 70 to 20 °C.

Evaluation of Strategies Aimed at Improving Liver Progenitor Cell Rolling and Subsequent Adhesion to the Endothelium.

Adult-derived human liver stem/progenitor cells (ADHLSCs) are a promising alternative to orthotopic liver transplantation in the treatment of inborn errors of metabolism. However, as is the case with many mesenchymal stromal cells, ADHLSCs have shown a low level of engraftment, which could be explained by the fact that they lack expression of selectin ligand and LFA-1 and only slightly express VLA- 4, molecules that have been shown to be involved in cell adhesion to the endothelium. In this paper, we have investigated strategies to increase their rolling and adhesion during the homing process by (1) adding a selectin ligand (Sialyl Lewis X) to their surface using biotinyl-N-hydroxy-succinimide-streptavidin bridges, and (2) protecting the adhesion proteins from trypsinization-induced damage using a thermosensitive polymer for cell culture and a nonenzymatic cell dissociation solution (CDS) for harvest. Despite increasing adhesion of ADHLSCs to E-selectin during an adhesion test in vitro performed under shear stress, the addition of Sialyl Lewis X did not increase adhesion to endothelial cells under the same conditions. Cultivating cells on a thermosensitive polymer and harvesting them with CDS increased their adhesion to endothelial cells under noninflammatory conditions, compared to the use of trypsin. However, we were not able to demonstrate any improvement in cell adhesion to the endothelium following culture on polymer and harvest with CDS, suggesting that alternative methods of improving engraftment still need to be evaluated.

Preparation and Characterization of Thermoresponsive Poly(N-Isopropylacrylamide) for Cell Culture Applications.

Poly(N-isopropylacrylamide) (PNIPAAm) is a typical thermoresponsive polymer used widely and studied deeply in smart materials, which is attractive and valuable owing to its reversible and remote "on-off" behavior adjusted by temperature variation. PNIPAAm usually exhibits opposite solubility or wettability across lower critical solution temperature (LCST), and it is readily functionalized making it available in extensive applications. Cell culture is one of the most prospective and representative applications. Active attachment and spontaneous detachment of targeted cells are easily tunable by surface wettability changes and volume phase transitions of PNIPAAm modified substrates with respect to ambient temperature. The thermoresponsive culture platforms and matching thermal-liftoff method can effectively substitute for the traditional cell harvesting ways like enzymatic hydrolysis and mechanical scraping, and will improve the stable and high quality of recovered cells. Therefore, the establishment and detection on PNIPAAm based culture systems are of particular importance. This review covers the important developments and recommendations for future work of the preparation and characterization of temperature-responsive substrates based on PNIPAAm and analogues for cell culture applications.

Thermosensitive molecularly imprinted poly(1-vinyl-2-pyrrolidone/methyl methacrylate/N-vinylcaprolactam) for selective extraction of imatinib mesylate in human biological fluid.

The efficiency of a molecularly imprinted polymer as a selective packing material for the solid-phase extraction of imatinib mesylate sorption was investigated. The molecularly imprinted polymer was prepared using N,N'-methylenebisacrylamide as a cross-linker agent, N-vinylcaprolactam as a thermo-sensitive monomer, 1-vinyl-2-pyrrolidone and methyl methacrylate as functional monomers, azobisisobutyronitrile as an initiator and imatinib mesylate as a template. The drug-imprinted polymer was identified by Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, and scanning electron microscopy. It was found that this polymer can be used for determination of trace levels of imatinib mesylate with a recovery percentage that could reach over 90%. Furthermore, the synthesized molecularly imprinted polymer indicated higher selectivity towards imatinib mesylate than other compounds. From isotherm study, the equilibrium adsorption data of imatinib mesylate by imprinted polymer were analyzed by Langmuir, Freundlich, and Temkin isotherm models. The developed method was used for determination of imatinib mesylate in human fluid samples by high performance liquid chromatography with excellent results.

Development and characterization of mucoadhesive-thermoresponsive gels for the treatment of oral mucosa diseases.

INTRODUCTION: The mucositis is an inflammatory, erosive and ulcerative process of the oral mucosa. It is usually caused by radiation, chemotherapy, infections, diabetes, smoking and it is characterized by severe pain and difficulty eating and can have a very serious impact on quality of life. A suitable treatment must ensure pain control and mechanical protection to promote mucosal healing. The purpose of this work was to study an in-situ gelling formulation to be sprayed onto the damaged oral mucosa by self-administration. The formulation must be able to quickly form a film when applied in the oral cavity. METHODS: many batches were prepared mixing a thermosensitive polymer (poloxamer PF127 or P123) with mucoadhesive polymers polyvinylpyrrolidone (PVP), sodium carboxymethyl cellulose (NaCMC), Carbopol 971P, chitosan (CS). By an experimental design three suitable formulations were identified and loaded with the model drug benzydamine hydrochloride. The hydrogel based on 25.50% PF127, 0.20% PVP and 0.35% CS maintained its original properties (gelling, rheological and mucoadhesive) after loading and showing a sustained drug release. CONCLUSIONS: the selected hydrogel showed to be suitable for the treatment of mucositis, able to reduce the number of daily administration and to protect the damaged mucosa from mechanical and chemical solicitations.

Smart thermosensitive chitosan hydrogel for nasal delivery of ibuprofen to treat neurological disorders.

BACKGROUND: The in-situ gelation of thermosensitive nasal formulations with desirable spray characteristics at room temperature and ability to undergo a phase change to a semi-solid state with mucoadhesive behavior at physiological temperature has the potential to efficiently deliver therapeutics to brain. However, their application in nasal spray generation with favorable characteristics has not been investigated. METHODS: Thermosensitive chitosan (CS)-based formulations with different viscosities were prepared for intranasal delivery of ibuprofen using CS of various molecular weights. The formulation developed was optimized with regards to its physicochemical, rheological, biological properties and the generated aerosol characteristics. RESULTS: The formulations showed rapid gelation (4-7 min) at 30-35°C, which lies in the human nasal cavity temperature spectrum. The decrease in CS molecular weight to 110-150 kDa led to generation of optimum spray with lower Dv50, wider spray area, and higher surface area coverage. This formulation also showed improved ibuprofen solubility that is approximately 100× higher than its intrinsic aqueous solubility, accelerated ibuprofen transport across human nasal epithelial cells and transient modulation of tight junctions. CONCLUSIONS: A thermosensitive CS-based formulation has been successfully developed with suitable rheological properties, aerosol performance and biological properties that is beneficial for nose-to-brain drug delivery.

Cleavable and thermo-responsive hybrid nanoparticles for on-demand drug delivery.

By combining the photothermal ability of copper sulphide nanoparticles (NPs) upon excitation with Near Infrared (NIR) Light and the thermo-responsive properties of the homemade oligo (ethylene glycol) methyl ether methacrylate copolymer we have obtained fragmentable nanocomposites able to release a carried drug on-demand after NIR-light triggering. A complete physico-chemical characterization of the resulting nanoparticles has been carried out and their degradation assessed at different temperatures. Herein, we have also evaluated the drug loading capacity of those nanoparticles and the temperature dependence in their drug release kinetics using bupivacaine hydrochloride as a model drug. For those hybrid nanoparticles, subcytotoxic doses on four different cell lines and their potential interference in cell metabolism, induction of apoptosis, and cell cycle have been evaluated by Alamar Blue fluorometry and flow cytometry.

Magnetic Nanoparticles Create Hot Spots in Polymer Matrix for Controlled Drug Release.

Herein, original magnetic drug delivery nanomaterials for cancer therapy are developed and compared, with the purpose to show active control over drug release by using an alternative magnetic field (AMF). The rationale is to combine polymers and superparamagnetic nanoparticles to trigger such drug release under AMF. Two magnetic nanosystems are thus presented: magnetic nanogels made of thermosensitive and biocompatible polymers and core-shell nanoparticles with a magnetic core and a molecularly imprinted polymer as shell. Both encapsulate doxorubicin (DOX) and the DOX controlled release was investigated in vitro and in cells under AMF excitation. It confirms that the local heat profile at the vicinity of the iron oxide core can be used for the DOX controlled release. It also shows that both nanosystems help delivering more DOX inside the cells compared to internalization of free DOX. Finally, the DOX intracellular release could be remotely triggered under AMF, in athermal conditions, thus enhancing DOX cytotoxicity.

Development a hydrazide-functionalized thermosensitive polymer based homogeneous system for highly efficient N-glycoprotein/glycopeptide enrichment from human plasma exosome.

As one of the most common post-translational modifications, protein N-glycosylation precipitates in many important biological processes and has closely correlations with the occurrence and progression of multiple diseases. Plasma exosomes secreted by cells contain various bioactive N-glycoproteins which may serve as potential biomarkers for early disease diagnosis and treatment. However, the protein N-glycosylation profile in human plasma exosome is largely unknown, due to the technical challenges in glycoprotein identification. Signals of the rare N-glycoproteins/N-glycopeptides are severely suppressed by the abundant coexisting non-glycosylated counterparts in mass spectrometry analysis. Therefore, specific enrichment of N-glycoprotein/glycopeptide is a prerequisite for large scale N-glycosylation profiling. In this work, we developed a hydrazide functionalized thermosensitive polymer for efficient enrichment and in-depth identification of protein N-glycosylation in human plasma exosome by mass spectrometry. The polymer chains completely dissolve in the enrichment system to form a homogeneous solution. Therefore, efficient covalent coupling between the N-glycoprotein/glycopeptide and the polymer chain is achieved, due to the reduced interfacial mass transfer resistance and the densely packed accessible functional groups on the polymer chains. Furthermore, the thermosensitive polymer can be easily precipitated and recovered by simply rising the system temperature to above 34 °C. As a result, 329 N-glycosylation sites corresponding to 180 N-glycoproteins were enriched and identified from plasma exosomes of glioma patients and healthy subjects using the thermosensitive polymer. By quantitative comparison, we found 26 N-glycoproteins significantly changed between the glioma patients and the healthy subjects, demonstrating the potential of this new strategy for N-glycoproteome research of plasma exosome and biomarker discovery.

Beyond Traditional Hyperthermia: In Vivo Cancer Treatment with Magnetic-Responsive Mesoporous Silica Nanocarriers.

In this study, we present an innovation in the tumor treatment in vivo mediated by magnetic mesoporous silica nanoparticles. This device was built with iron oxide magnetic nanoparticles embedded in a mesoporous silica matrix and coated with an engineered thermoresponsive polymer. The magnetic nanoparticles act as internal heating sources under an alternating magnetic field (AMF) that increase the temperature of the surroundings, provoking the polymer transition and consequently the release of a drug trapped inside the silica pores. By a synergic effect between the intracellular hyperthermia and chemotherapy triggered by AMF application, significant tumor growth inhibition was achieved in 48 h after treatment. Furthermore, the small magnetic loading used in the experiments indicates that the treatment is carried out without a global temperature rise of the tissue, which avoids the problem of the necessity to employ large amounts of magnetic cores, as is common in current magnetic hyperthermia.