Thermosensitive Nanoparticles Research Articles

Reengineering of Donor-Acceptor-Donor Structured Near-Infrared II Aggregation-Induced Emission Luminogens for Starving-Photothermal Antitumor and Inhibition of Lung Metastasis.

Electron acceptor possessing strong electron-withdrawing ability and exceptional stability is crucial for developing donor-acceptor-donor (D-A-D) structured aggregation-induced emission luminogens (AIEgens) with second near-infrared (NIR-II) emission. Although 6,7-diphenyl-[1,2,5] thiadiazolo [3,4-g] quinoxaline (PTQ) and benzobisthiadiazole (BBT) are widely employed as NIR-II building blocks, they still suffer from limited electron-withdrawing capacity or inadequate chemo-stability under alkaline conditions. Herein, a boron difluoride formazanate (BFF) acceptor is utilized to construct NIR-II AIEgen, which exhibits a better overall performance in terms of NIR-II emission and chemo-stability compared to the PTQ- and BBT-derived fluorophores. With finely tuned intramolecular motions and strong D-A interaction strength, TPE-BFF simultaneously exhibits high molar extinction coefficient (ε= 4.31 × 104 M-1cm-1), strong NIR-II emission (Φ = 0.49%) and photothermal effect (η = 58.5%), as well as high stability. Thanks to these merits, the thermosensitive nanoparticles constructed by integrating TPE-BFF and the antiglycolytic agent 2-deoxy-d-glucose (2DG) are successfully utilized for imaging-guided photothermal antitumor lung metastasis by regulating glycolysis and reducing ATP-dependent heat shock proteins. Combining experimental results and theoretical calculations, BFF proves to be an outstanding electron acceptor for the design of versatile NIR-II AIEgens. Overall, this study offers a promising alternative for developing multifunctional NIR-II AIEgens in biomedical applications.

NIR-Triggered Thermosensitive Nanoreactors for Dual-Guard Mechanism-Mediated Precise and Controllable Cancer Chemo-Phototherapy.

Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.

Mitochondria-Mediated HSP Inhibition Strategy for Enhanced Low-Temperature Photothermal Therapy.

Low-temperature photothermal therapy (PTT) has the advantage of causing less damage to normal tissues and has attracted great attention in recent years. However, the efficacy of low-temperature PTT is restricted by the overexpression of heat shock proteins (HSPs), specifically HSP70 and HSP90. Inhibiting the function of these HSPs is a major strategy used in the development of new cancer therapies. Herein, we designed four T780T-containing thermosensitive nanoparticles to interrupt the energy supply for HSP expression using their TPP-based mitochondrial targeting action. The reversal behavior of the nanoparticles on the gambogic acid (GA)-induced compensatory increase of HSP70 was investigated in vitro by Western blot and in vivo by immunohistochemistry. The in vivo anticancer efficacy of the low-temperature PTT based on these thermosensitive nanoparticles was also systematically examined. The design proposes for the first time to utilize and elucidate the mechanism of the mitochondrial targeting of T780T-containing NPs in synergy with the HSP90 inhibition of GA to achieve an effective low-temperature PTT. This work not only provides a novel pathway for the dual inhibition of HSP70 and HSP90 but also opens up a new approach for low-temperature PTT of tumors.

Anti-cancer activity of naringenin loaded smart polymeric nanoparticles in breast cancer

Breast cancer is the most common form of cancer among women worldwide, and approximately comprise 25% of all female malignancies. Naringenin (Nar) is a promising anticancer agent for breast cancer. However, its use as a therapeutic agent is limited due to its poor water solubility and bioavailability. The purpose of the present study is to prepare pH and thermo sensitive smart polymeric nanoparticles carrying naringenin (NarSPNPs) to improve bioavailability, and increase therapeutic efficacy against breast cancer. N-isopropylacrylamide and Vinyl imidazole were used as thermo and pH sensitive monomers, respectively. NarSPNPs were characterized using dynamic light scattering (DLS) analyses, SEM and FTIR for particle size and potential analysis, surface morphology and functional group determinations, respectively. Release profile and its effects on cell proliferation, apoptosis and cell cycle in breast cancer were also studied. Physicochemical characterization of newly prepared NarSPNPs, cytotoxicity, and IC50 assessments confirmed their stability and bioactivity as an anti-breast cancer agent with no toxicity against human epithelia cells. These findings together with flow cytometry analysis, revealed that apoptosis is the main mechanism underlying cell death after NarSPNPs treatment.

Thermosensitive chitosan/poly(N-isopropyl acrylamide) nanoparticles embedded in aniline pentamer/silk fibroin/polyacrylamide as an electroactive injectable hydrogel for healing critical-sized calvarial bone defect in aging rat model

Thermosensitive nanoparticles with phase transition abilities have been considered as suitable materials in biomedical fields, especially drug delivery systems. Moreover, electroactive injectable hydrogels supporting bone regeneration of the elderly will highly be desired in bone tissue engineering applications. Herein, thermosensitive nanoparticles were fabricated using chitosan/poly(N-isopropyl acrylamide) for simvastatin acid delivery. The nanoparticles were incorporated into electroactive injectable hydrogels based on aniline pentamer/silk fibroin/polyacrylamide containing vitamin C. The nanoparticles had thermosensitive properties as simvastatin acid had higher release rates at 37 than 23 °C without significant burst release. The hydrogels also revealed an appropriate gelation time, stable mechanical and rheological characteristics, high water absorbency, and proper biodegradability. In vitro studies indicated that the hydrogel was biocompatible and nontoxic, especially those containing drugs. Implantation of the hydrogels containing both simvastatin acid and vitamin C into the critical calvarial bone defect of the aged rat also demonstrated significant enhancement of bone healing after 4 and 8 weeks post-implantation. We found that the electroactive injectable hydrogels containing thermosensitive nanoparticles exhibited great potential for treating bone defects in the elderly rats

Vinyl copolymers with faster hydrolytic degradation than aliphatic polyesters and tunable upper critical solution temperatures

Vinyl polymers are the focus of intensive research due to their ease of synthesis and the possibility of making well-defined, functional materials. However, their non-degradability leads to environmental problems and limits their use in biomedical applications, allowing aliphatic polyesters to still be considered as the gold standards. Radical ring-opening polymerization of cyclic ketene acetals is considered the most promising approach to impart degradability to vinyl polymers. However, these materials still exhibit poor hydrolytic degradation and thus cannot yet compete with traditional polyesters. Here we show that a simple copolymerization system based on acrylamide and cyclic ketene acetals leads to well-defined and cytocompatible copolymers with faster hydrolytic degradation than that of polylactide and poly(lactide-co-glycolide). Moreover, by changing the nature of the cyclic ketene acetal, the copolymers can be either water-soluble or can exhibit tunable upper critical solution temperatures relevant for mild hyperthermia-triggered drug release. Amphiphilic diblock copolymers deriving from this system can also be formulated into degradable, thermosensitive nanoparticles by an all-water nanoprecipitation process.

Dual Targeting of Cancer Cells and MMPs with Self-Assembly Hybrid Nanoparticles for Combination Therapy in Combating Cancer.

The co-delivery of chemotherapeutic agents and immune modulators to their targets remains to be a great challenge for nanocarriers. Here, we developed a hybrid thermosensitive nanoparticle (TMNP) which could co-deliver paclitaxel-loaded transferrin (PTX@TF) and marimastat-loaded thermosensitive liposomes (MMST/LTSLs) for the dual targeting of cancer cells and the microenvironment. TMNPs could rapidly release the two payloads triggered by the hyperthermia treatment at the site of tumor. The released PTX@TF entered cancer cells via transferrin-receptor-mediated endocytosis and inhibited the survival of tumor cells. MMST was intelligently employed as an immunomodulator to improve immunotherapy by inhibiting matrix metalloproteinases to reduce chemokine degradation and recruit T cells. The TMNPs promoted the tumor infiltration of CD3+ T cells by 2-fold, including memory/effector CD8+ T cells (4.2-fold) and CD4+ (1.7-fold), but not regulatory T cells. Our in vivo anti-tumor experiment suggested that TMNPs possessed the highest tumor growth inhibitory rate (80.86%) compared with the control group. We demonstrated that the nanoplatform could effectively inhibit the growth of tumors and enhance T cell recruitment through the co-delivery of paclitaxel and marimastat, which could be a promising strategy for the combination of chemotherapy and immunotherapy for cancer treatment.

Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy.

Simple SummaryMild hyperthermia is a technique that induces a local tumor temperature increase up to 43.0 °C. In this paper, we introduce three devices that could be used to apply hyperthermia in small animals in combination with intravital microscopy for the real-time visualization of in vivo intratumoral events such as drug delivery.This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.

Fabrication of composite Fe3O4 nanoparticles coupled by thermo-responsive and fluorescent Eu complex on surface

Stimuli-responsive luminescent hybrid nanoparticles consisting of a magnetite Fe3O4 core and a hydrophilic outer shell were synthesized. The shell was a thermo-responsive Eu(III) complex shell, which was synthesized as follows: first, 3-Methacryloxypropyl-trimethoxysilane (MEMO)-co-poly(N-isopropylacrylamide) (NIPAM) (MEMO-co-PNIPAM) copolymer was prepared by free radical polymerization. Subsequently, the copolymer chelated with Europium(III) ions to form a luminescent polymeric layer. Finally, the polymeric shell was grafted onto the Fe3O4 nanoparticles surface through chemical action. The sizes of fabricated nanoparticles with core–shell structure were controlled at about 30-45 nm. The as-synthesized nanocomposite particles had excellent fluorescence performance and thermo-responsive behavior, which possessed high color purity and produced red-emission at 613 nm. The lower critical solution temperature (LCST) of thermo-sensitive magnetic nanoparticles was at around 37–38 °C. Cell viability assays suggested that these nanoparticles showed excellent biocompatibility and fluorescence-intensity in vitro.

Thermosensitive Nanoparticles Based on Polyethylenimine as Promising Materials for Biomedical Applications

Thermosensitive nanoparticles were synthesized by acylation of branched polyethyleneimine with isobutyroyl chloride and cross-linking by 1,6-hexamethylene diisocyanate. It was found that colloidal aqueous solutions of these particles reversibly lose solubility around physiological temperature. The influence of the composition of the nanoparticle on their hydrodynamic parameters, as well as on the phase transition temperatures in aqueous solutions was evaluated.

PD08-11 REAL-TIME MONITORING OF RADIOFREQUENCY ABLATION RANGE OF RENAL TUMORS BY THERMOSENSITIVE LIPID NANOPARTICLES

You have accessJournal of UrologyKidney Cancer: Localized: Ablative Therapy (PD08)1 Apr 2020PD08-11 REAL-TIME MONITORING OF RADIOFREQUENCY ABLATION RANGE OF RENAL TUMORS BY THERMOSENSITIVE LIPID NANOPARTICLES Linfang Yao*, Guanchen Zhu, Wenmin Cao, Wei Wang, Wei Chen, Ming Chen, Xingqun Zhao, and Hongqian Guo Linfang Yao*Linfang Yao* More articles by this author , Guanchen ZhuGuanchen Zhu More articles by this author , Wenmin CaoWenmin Cao More articles by this author , Wei WangWei Wang More articles by this author , Wei ChenWei Chen More articles by this author , Ming ChenMing Chen More articles by this author , Xingqun ZhaoXingqun Zhao More articles by this author , and Hongqian GuoHongqian Guo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000835.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To explore the feasibility of assessing intraoperative radiofrequency ablation coverage by using novel thermosensitive lipid nanoparticles contained with liquid perfluorohexane. METHODS: In this experiment, a new kind of thermosensitive lipid nanoparticle contained with liquid perfluorohexane was prepared by rotating evaporation and acoustic resonance method, which could be changed from liquid to gas quickly at 58-60 °C. Thermal phase transition of nanoparticles was observed in vitro water capsule heating experiment and agar-agar gel model radiofrequency ablation experiment. In vivo rabbit kidney VX2 tumor model was used for ultrasound imaging with the nanoparticles. Radiofrequency ablation alone and radiofrequency ablation combined with this thermosensitive nanoparticles were performed respectively. The formation of gasification area was observed with ultrasonic measuring system (Flex Focus 800 (BK Medical). The boundary temperature of the gasification zone was detected by the temperature measuring system(NATIONAL INSTRUMENTS Company, USA). The size of gasification area and gross pathology were measured, and their correlation was analyzed. RESULTS: Through in vitro characterization, the size of this nanoparticles was confirmed to be about 300nm. In vitro ultrasound experiments showed that the echo of thermosensitive lipid nanoparticles was significantly enhanced compared with that before heating. Radiofrequency ablation of rabbit renal VX2 tumor in vivo showed that thermosensitive lipid nanoparticles made the gasification zone generated by radiofrequency ablation more obvious, and the boundary temperature of the gasification zone was about 60?. The gasification zone is larger than the radiofrequency ablation range, and highly correlated with gross pathologic necrosis zone. CONCLUSIONS: Thermosensitive lipid nanoparticles contained with liquid perfluorohexane have the potential of thermosensitive phase transition. It is expected to be a new method for intraoperative real-time monitoring and evaluation of radiofrequency ablation boundaries. Source of Funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81972388, 81772710) , Nanjing health science and technology development special fund project?YKK18076?,Jiangsu postdoctoral research fund?1701023B?, the Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Key Medical Discipline (Laboratory) (ZDXKB2016014). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e172-e173 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Linfang Yao* More articles by this author Guanchen Zhu More articles by this author Wenmin Cao More articles by this author Wei Wang More articles by this author Wei Chen More articles by this author Ming Chen More articles by this author Xingqun Zhao More articles by this author Hongqian Guo More articles by this author Expand All Advertisement PDF downloadLoading ...

Thermosensitive N-isopropylacrylamide Nanoparticles Hydrogel Application on Biomolecules Identification

Intelligent hydrogel is hydrophilic polymer gel which is immiscible but significantly swells in water. Thermosensitive nanoparticles hydrogel is a kind of intelligent hydrogels, and its volume phase could change with the external temperature value resulting to its typical of low critical solution temperature. It has extraordinary nanometer characterization and sensitivity to the stimulus of the environmental conditions. In recent years, thermosensitive N-isopropylacrylamide nanoparticles hydrogel are one of the hotspots in hydrogels research. They have attracted much attention in the field of biomedicine due to their good biocompatibility and sensitive temperature response. Thermosensitive N-isopropylacrylamide nanoparticles hydrogel show good application prospects in drug delivery system, protein separation, medical diagnosis, biosensors, biomaterials and other fields. In this paper, the application research and development prospect of N-isopropylacrylamide thermosensitive nanoparticles hydrogel in macromolecule recognition was mainly summarized from protein to peptide. Moreover, the employ of nanoparticles in drug delivery and release, and capillary electrophoresis for DNA separation were also overviewed. Further promising applications of this biological material in macromolecule recognition are ever-accelerated. It is expected that thermosensitive N-isopropylacrylamide nanoparticles hydrogel will break through the limitations of biomedical field and be widely used in other fields.

Sustained co-delivery of ibuprofen and basic fibroblast growth factor by thermosensitive nanoparticle hydrogel as early local treatment of peri-implantitis.

ObjectiveThe aims of this study were to 1) encapsulate ibuprofen (IBU) and basic fibroblast growth factor (bFGF) in a thermosensitive micellar hydrogel, 2) test the biological properties of this in situ drug delivery system, and 3) study the effect of hydrogel in promoting soft tissue healing after implant surgery and its anti-inflammatory function as an early local treatment of peri-implantitis.Materials and methodsA thermosensitive micellar hydrogel was prepared from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone) (PECT) nanoparticles and tested in vitro using a scanning electron microscope, rheometer, UV spectrophotometer, HPLC, and transmission electron microscope.ResultsThe bFGF + IBU/PECT hydrogel formed a stable, water-dispersible nanoparticle core shell that was injectable at room temperature, hydrogel in situ at body temperature, and provided sustained release of both hydrophilic and hydrophobic drugs. The hydrogel promoted the proliferation and adhesion of human gingival fibroblasts, upregulated the expression of adhesion factors such as vinculin proteins, and showed anti-inflammatory properties.ConclusionIn situ preparation of IBU-and bFGF-loaded PECT hydrogel represents a promising drug delivery system with the potential to provide early local treatment for peri-implantitis.

Co-delivery of Doxorubicin and Interferon-γ by Thermosensitive Nanoparticles for Cancer Immunochemotherapy.

A dual-sensitive nanoparticle delivery system was constructed by incorporating an acid sensitive hydrazone linker into thermosensitive nanoparticles (TSNs) for co-encapsulating doxorubicin (DOX) and interferon γ (IFNγ) and to realize the co-delivery of chemotherapy and immunotherapy agents against melanoma. DOX, a chemotherapeutic drug, was conjugated to TSNs by a pH-sensitive chemical bond, and IFNγ, a potent immune-modulator, was absorbed into TSNs through the thermosensitivity and electrostatics of nanoparticles. Consequently, the dual sensitive drug-loaded TSN delivery systems were successfully built and showed an obvious core-shell structure, good encapsulation efficiency of drugs, sustained and sensitive drug release, prolonged circulation time, as well as excellent synergistic antitumor efficiency against B16F10 tumor bearing mice. Moreover, the combinational antitumor immune responses of hydrazone bearing DOX/IFNγ-TSN (hyd) were strengthened by activating Th1-type CD4+ T cells, cytotoxic T lymphocytes, and natural killer cells, downregulating the expression levels of immunosuppressive cytokines, such as IL10 and TGFβ, and upregulating the secretion of IL2 and TNFα. Taken together, the multifunctional TSNs system provides a promising strategy for multiple drugs co-delivery with distinct properties.

A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles

The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

Preparation of a novel injectable in situ-gelling nanoparticle with applications in controlled protein release and cancer cell entrapment.

Temperature sensitive injectable hydrogels have been used as drug/protein carriers for a variety of pharmaceutical applications. Oligo(ethylene glycol) methacrylate (OEGMA) monomers with varying ethylene oxide chain lengths have been used for the synthesis of in situ forming hydrogel. In this study, a new series of thermally induced gelling hydrogel nanoparticles (PMOA hydrogel nanoparticles) was developed by copolymerization with di(ethylene glycol) methyl ether methacrylate (MEO2MA), poly(ethylene glycol) methyl ether methacrylate (300 g mol−1, OEGMA300), and acrylic acid (AAc). The effects of acrylic acid content on the physical, chemical, and biological properties of the nanoparticle-based hydrogels were investigated. Due to its high electrostatic properties, addition of AAc increases LCST as well as gelation temperature. Further, using Cy5-labelled bovine serum albumin and erythropoietin (Epo) as model drugs, studies have shown that the thermogelling hydrogels have the ability to tune the release rate of these proteins in vitro. Finally, the ability of Epo releasing hydrogels to recruit prostate cancer cells was assessed in vivo. Overall, our results support that this new series of thermally induced gelling systems can be used as protein control releasing vehicles and cancer cell traps.

Hydrodynamic Cavitation through “Labs on a Chip”: From Fundamentals to Applications

Monitoring hydrodynamic cavitation of liquids through “labs on a chip” (i.e . microchannels with a shrinkage, such as microdiaphragms or microventuris) is an improvement in experimental approaches devoted to study the mechanisms involved in these multiphase flows. The small sizes of the reactors do not require big substructures. Flow rates of around 1 L/h make possible the characterisation of rare, toxic or expensive pure fluids or mixtures. Moreover, because of that microfluidic approach, an unique inception of the cavitation from a laminar flow regime is also possible, that provides precious databases for simulation or modelisation. Lastly, “labs on a chip” are an extremely versatile solution to perform novel experiments, as they are embeddable in tools basically designed to proceed with small samples (confocal microscopy, spectroscopy). We present here a summary of the former experiments performed by our team, concerning the fundamental aspects of hydrodynamic cavitation in a microchannel. We have recorded, with thermosensitive nanoparticles dispersed in water, the thermal signature of the growth and collapse of bubbles. We were also able to monitor the cavitation flow regime from a laminar single liquid phase. We are currently involved in applicative studies of hydrodynamic cavitation in microchannels, and preliminary results concerning liquid phase exfoliation of graphene will be also presented.

Thermoresponsive mesoporous silica nanoparticles as a carrier for skin delivery of quercetin

Recently, mesoporous silica nanoparticles (MSNs) have emerged as promising drug delivery systems able to preserve the integrity of the carried substance and/or to selectively reach a target site; however, they have rarely been explored for skin application. In this study, thermoresponsive MSNs, designed to work at physiologic cutaneous temperature, are proposed as innovative topical carriers for quercetin (Q), a well-known antioxidant. The thermosensitive nanoparticles were prepared by functionalizing two different types of matrices, with pore size of 3.5nm (MSNsmall) and 5.0nm (MSNbig), carrying out a free radical copolymerization of N-isopropylacrylamide (NIPAM) and 3-(methacryloxypropyl)trimethoxysilane (MPS) inside the mesopores. The obtained copolymer-grafted MSNs (copoly-MSNs) were physico-chemically characterized and their biocompatibility was attested on a human keratinocyte cell line (HaCaT). The release profiles were assessed and the functional activity of Q, free or loaded, was evaluated in terms of antiradical and metal chelating activities. Ex vivo accumulation and permeation through porcine skin were also investigated. The characterization confirmed the copolymer functionalization of the MSNs. In addition, both the bare and functionalized silica matrices were found to be biocompatible. Among the copolymer-grafted complexes, Q/copoly-MSNbig exhibited more evident thermoresponsive behavior proving the potential of these thermosensitive systems for advanced dermal delivery.

Controlled release of anti-inflammatory peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation

Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-inflammatory peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.

Self-assembled thermosensitive nanoparticles based on oligoethylene glycol dendron conjugated doxorubicin: preparation, and efficient delivery of free doxorubicin

An amphiphilic dendron–drug conjugate was synthesized via oligoethylene glycol (OEG) dendrons coupled with anticancer drug doxorubicin (DOX).