The porphyrin-cyclodextrin conjugates were prepared and tested for selective and effective multifunctional drug delivery and therapy. The porphyrin receptor system combines efficient binding of the selected drug to the cyclodextrin cavity and photosensitizing properties of the porphyrin moiety with high accumulation of the whole complex in cancer tissue. The combined effect of chemotherapy and photodynamic therapy is demonstrated by in vitro and in vivo studies.

• MeSH
• buněčná smrt účinky léků   MeSH
• cyklodextriny farmakologie   chemická syntéza   chemie   MeSH
• kombinovaná terapie MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   patologie   MeSH
• nanotechnologie MeSH
• porfyriny farmakologie   chemická syntéza   chemie   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   chemická syntéza   chemie   MeSH
• screeningové testy protinádorových léčiv MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The development of anticancer drug delivery systems which retain or enhance the cytotoxic properties of the drug to tumorous tissues, while reducing toxicity to other organs is of key importance. We investigated different poly(methacrylic acid)-g-poly(ethyleneglycol methacrylate) polymers as in situ coating agents for magnetite nanocrystallites. The obtained magnetic nano-assemblies were in turn thoroughly characterized for their structural, colloidal and physicochemical properties (drug loading capacity/release, magnetic field triggered drug release, cell uptake and localization) in order to select the best performing system. With the focus on in vivo validation of such magnetic drug delivery systems for first time, we selected cisplatin as the drug, since it is a potent anticancer agent which exhibits serious side effects due to lack of selectivity. In addition, cisplatin would offer facile determination of the metal content in the animal tissues for biodistribution studies. Alongside post-mortem Pt determination in the tissues, the biodistribution of the drug nanocarriers was also monitored in real time with PET-CT (positron emission tomography/computed tomography) with and without the presence of magnetic field gradients; using a novel chelator-free method, the nanoparticles were radiolabeled with 68Ga without having to alter their structure with chemical modifications for conjugation of radiochelators. The ability to be radiolabeled in such a straightforward but very robust way, along with their measured high MRI response, renders them attractive for dual imaging, which is an important functionality for translational investigations. Their anticancer properties were evaluated in vitro and in vivo, in a cisplatin resistant HT-29 human colon adenocarcinoma model, with and without the presence of magnetic field gradients. Enhanced anticancer efficacy and reduced toxicity was recorded for the cisplatin-loaded nanocarriers in comparison to the free cisplatin, particularly when a magnetic field gradient was applied at the tumor site. Post mortem and real-time tissue distribution studies did not reveal increased cisplatin concentration in the tumor site, suggesting that the enhanced anticancer efficacy of the cisplatin-loaded nanocarriers is driven by mechanisms other than increased cisplatin accumulation in the tumors.

• MeSH
• adenokarcinom farmakoterapie   patologie   MeSH
• buňky HT-29 MeSH
• chemorezistence MeSH
• cisplatina aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• kyseliny polymethakrylové chemie   MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• magnetické nanočástice * MeSH
• methakryláty chemie   MeSH
• myši nahé MeSH
• myši SCID MeSH
• nádory tračníku farmakoterapie   patologie   MeSH
• PET/CT MeSH
• polyethylenglykoly chemie   MeSH
• protinádorové látky aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• tkáňová distribuce MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

Advanced drug delivery micro- and nanosystems have been widely explored due to their appealing specificity/selectivity, biodegradability, biocompatibility, and low toxicity. They can be applied for the targeted delivery of pharmaceuticals, with the benefits of good biocompatibility/stability, non-immunogenicity, large surface area, high drug loading capacity, and low leakage of drugs. Cardiovascular diseases, as one of the primary mortalities cause worldwide with significant impacts on the quality of patients' life, comprise a variety of heart and circulatory system pathologies, such as peripheral vascular diseases, myocardial infarction, heart failure, and coronary artery diseases. Designing novel micro- and nanosystems with suitable targeting properties and smart release behaviors can help circumvent crucial challenges of the tolerability, low stability, high toxicity, and possible side- and off-target effects of conventional drug delivery routes. To overcome different challenging issues, namely physiological barriers, low efficiency of drugs, and possible adverse side effects, various biomaterials-mediated drug delivery systems have been formulated with reduced toxicity, improved pharmacokinetics, high bioavailability, sustained release behavior, and enhanced therapeutic efficacy for targeted therapy of cardiovascular diseases. Despite the existing drug delivery systems encompassing a variety of biomaterials for treating cardiovascular diseases, the number of formulations currently approved for clinical use is limited due to the regulatory and experimental obstacles. Herein, the most recent advancements in drug delivery micro- and nanosystems designed from different biomaterials for the treatment of cardiovascular diseases are deliberated, with a focus on the important challenges and future perspectives.

• MeSH
• biokompatibilní materiály MeSH
• kardiovaskulární nemoci * farmakoterapie   MeSH
• lékové transportní systémy MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• příprava léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Alginates have been widely explored due to their salient advantages of hydrophilicity, biocompatibility, mucoadhesive features, bioavailability, environmentally-benign properties, and cost-effectiveness. They are applied for designing micro- and nanosystems for controlled and targeted drug delivery and cancer therapy as alginate biopolymers find usage in encapsulating anticancer drugs to improve their bioavailability, sustained release, pharmacokinetics, and bio-clearance. Notably, these nanomaterials can be applied for photothermal, photodynamic, and chemodynamic therapy of cancers/tumors. Future explorations ought to be conducted to find novel alginate-based (nano)systems for targeted cancer therapy using advanced drug delivery techniques with benefits of non-invasiveness, patient compliance, and convenience of drug administration. Thus, some critical parameters such as mucosal permeability, stability in the gastrointestinal tract environment, and drug solubility ought to be considered. In addition, the comprehensive clinical translational studies along with the optimization of synthesis techniques still need to be addressed. Herein, we present an overview of the current state of knowledge and recent developments pertaining to the applications of alginate-based micro- and nanosystems for targeted cancer therapy based on controlled drug delivery, photothermal therapy, and chemodynamic/photodynamic therapy approaches, focusing on important challenges and future directions.

• MeSH
• algináty * MeSH
• biologická dostupnost MeSH
• lékové transportní systémy metody   MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• nádory * farmakoterapie   MeSH
• rozpustnost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Inflammatory diseases, whether caused by excessive stress on certain tissues/parts of the body or arising from infections accompanying autoimmune or secondary diseases, have become a problem, especially in the Western world today. Whether these are inflammations of visceral organs, joints, bones, or the like, they are always a physiological reaction of the body, which always tries to eradicate noxious agents and restore tissue homeostasis. Unfortunately, this often results in damage, often irreversible, to the affected tissues. Nevertheless, these inflammatory reactions of the body are the results of excessive stress, strain, and the generally unhealthy environment, in which the people of Western civilization live. The pathophysiology and pathobiochemistry of inflammatory/autoimmune processes are being studied in deep detail, and pharmaceutical companies are constantly developing new drugs that modulate/suppress inflammatory responses and endogenous pro-inflammatory agents. In addition to new specifically targeted drugs for a variety of pro-inflammatory agents, a strategy can be found for the use of older drugs, which are formulated into special nanodrug delivery systems with targeted distribution and often modified release. This contribution summarizes the current state of research and development of nanoformulated anti-inflammatory agents from both conventional drug classes and experimental drugs or dietary supplements used to alleviate inflammatory reactions.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The use of natural compounds is becoming increasingly popular among patients, and there is a renewed interest among scientists in nature-based bioactive agents. Traditionally, herbal drugs can be taken directly in the form of teas/decoctions/infusions or as standardized extracts. However, the disadvantages of natural compounds, especially essential oils, are their instability, limited bioavailability, volatility, and often irritant/allergenic potential. However, these active substances can be stabilized by encapsulation and administered in the form of nanoparticles. This brief overview summarizes the latest results of the application of nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers used as drug delivery systems of herbal essential oils or used directly for their individual secondary metabolites applicable in cancer therapy. Although the discussed bioactive agents are not typical compounds used as anticancer agents, after inclusion into the aforesaid formulations improving their stability and bioavailability and/or therapeutic profile, they indicated anti-tumor activity and became interesting agents with cancer treatment potential. In addition, co-encapsulation of essential oils with synthetic anticancer drugs into nanoformulations with the aim to achieve synergistic effect in chemotherapy is discussed.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cíl: Cílem projektu je navrhnout a ověřit nanokonstrukt jako inovativní nástroj pro efektivní zacílení na bakteriální buňku. Metodika: Konstrukt SPIONs/ Au/NPs/AB1/GF/AgNPsGS/ APO/ATB je tvořen: A – stříbrná nanočástice, která byla připravena zelenou syntézou z rostlinných extraktů (AgNPsGS); B – apoferitin (APO) s enkapsulovaným antibiotikem (ATB); C – superparamagnetická zlatá nanočástice modifikovaná grafenovým listem a protilátkou (SPIONs/Au/NPs/AB1/GF). Výsledky: Nejlepší antibakteriální efekt k S. aureus byl pozorován u AgNPsGS4 (Thymus serpyllum): 0,4 μg/ ml. Efektivita enkapsulace antibiotika do nanometrické struktury apoferitinu byla okolo 15 % aplikované koncentrace. V přítomnosti nanokonstruktu byla zaznamenána dramatická inhibice S. aureus. Biologický efekt nanotransportérů spočívá ve dvou hlavních mechanismech. AgNPsGS indukují vznik reaktivních kyslíkových radikálů (ROS reactive oxygen species), což následně vede k poškození buněčné membrány bakteriální buňky a k destrukci prokaryotické nukleové kyseliny. Kromě efektu AgNPsGS se uplatňuje i účinek enkapsulovaného ATB, který se podílí na léčbě bakteriální infekce a který lze vhodně zvolit podle typu infekčního onemocnění. Dále svou roli také sehrává významný synergický efekt AgNPsGS a ATB. Závěr: Díky inovativnímu a funkčnímu spojení účinku AgNPsGS a ATB dochází ke vzniku jedinečného terapeutického nanosystému pro cílenou terapii vážných bakteriálních infekcí.

Aim: The aim of the project was to design and verify the nanoconstruct as an innovative tool for effective targeting to the bacterial cell. Methods: The SPIONs/Au/ NPs/AB1/GF/AgNPsGS/APO/ ATB construct consists of: A – a silver nanoparticle prepared by green synthesis using plant extracts (AgNPsGS); B – apoferritin (APO) with the encapsulated antibiotic (ATB); and C – a superparamagnetic gold nanoparticle modified with graphene sheet and antibody (SPIONs/Au/NPs/AB1/GF). Results: The highest antibacterial effect (Staphylococcus aureus) was observed in AgNPsGS4 (Thymus serpyllum) at a concentration of 0.4 μg/mL. The effectiveness of encapsulation of the antibiotic into the nanometric structure of apoferritin was about 15% of the applied concentration. Dramatic inhibition of S. aureus was observed in the presence of the nanoconstruct. The biological effect of nanotransporter consists in two main mechanisms. AgNPsGS induce the formation of ROS, which subsequently leads to damage to the bacterial cell membrane and destruction of prokaryotic nucleic acid. In addition to the effect of AgNPsGS, the effect of encapsulated ATB is involved in the treatment of bacterial infection. This antibiotic can be appropriately selected according to the type of infectious disease. Furthermore, a significant synergistic effect of AgNPsGS and ATB also plays a role. Conclusion: Due to the innovative and functional combination of the effects of AgNPsGS and ATB, a unique therapeutic nanosystem was created.

• MeSH
• antibakteriální látky MeSH
• apoferritiny chemie   terapeutické užití   MeSH
• bakteriální infekce * farmakoterapie   MeSH
• fotosyntéza MeSH
• kovové nanočástice * chemie   MeSH
• lidé MeSH
• rostlinné extrakty MeSH
• stříbro chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

To improve the treatment of psoriasiform inflammation, we developed actively targeted nanocarriers loaded with the phosphodiesterase 4 inhibitor AN2728. Methods: Phospholipid-poly(lactic-co-glycolic acid) nanohybrids were prepared and conjugated with monovalent anti-desmoglein 3 antibody to bind keratinocytes. Results: The actively targeted nanohybrids were 229 nm in mean size with a nearly neutral surface charge. Flow cytometry and confocal microscopy showed a 9-fold increase in keratinocyte uptake of targeted nanohybrids relative to non-targeted nanoparticles. The nanoparticles localized mainly in lysosomes after internalization. AN2728-loaded antibody-conjugated nanocarriers inhibited cytokine/chemokine overexpression in activated keratinocytes without affecting cell viability. The targeted nanohybrids also suppressed neutrophil migration by reducing CXCL1 and CXCL2 release from keratinocytes. Following subcutaneous administration in mice, the nanohybrids distributed to the epidermis and hair follicles. In a psoriasis-like skin mouse model, the actively targeted nanoparticles were superior to free drug and non-targeted nanoparticles in mitigating skin inflammation. Intervention with the targeted nanosystem reduced the epidermal thickness of the psoriasiform lesion from 191 to 42 µm, decreased the Psoriasis Area Severity Index by 74%, restored barrier function, and returned chemokine levels to baseline. Conclusions: Our developed nanosystem was safe and demonstrated efficient targeting properties for the treatment of cutaneous inflammation.

• MeSH
• bicyklické sloučeniny heterocyklické aplikace a dávkování   farmakologie   MeSH
• buněčné linie keratinocytů HaCaT MeSH
• chemokin CXCL1 účinky léků   imunologie   MeSH
• chemokin CXCL2 účinky léků   imunologie   MeSH
• chemotaxe účinky léků   MeSH
• desmoglein 3 imunologie   MeSH
• epidermis MeSH
• fosfolipidy * MeSH
• imunokonjugáty farmakologie   MeSH
• inhibitory fosfodiesterasy 4 aplikace a dávkování   farmakologie   MeSH
• keratinocyty účinky léků   imunologie   MeSH
• kopolymer kyseliny glykolové a mléčné * MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• lyzozomy metabolismus   ultrastruktura   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nanočástice * MeSH
• neutrofily účinky léků   MeSH
• nosiče léků MeSH
• protilátky imunologie   MeSH
• psoriáza imunologie   patologie   MeSH
• sloučeniny boru aplikace a dávkování   farmakologie   MeSH
• vlasový folikul MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Purpose: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer. Methods: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity. Results: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions. Conclusion: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles' self-monitoring function has been developed, opening up new ideas for combined tumor therapy.

• MeSH
• apoptóza účinky léků   MeSH
• buněčná smrt účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• dánio pruhované MeSH
• endocytóza účinky léků   MeSH
• fluorescence MeSH
• irinotekan farmakologie   terapeutické užití   MeSH
• kurkumin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   MeSH
• nanočástice chemie   MeSH
• nosiče léků MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH