RESUMEN
Developing optical tumor imaging probes with minimal background noise is very important for its early detection of small lesions and accurate diagnosis of cancer. To overcome the bottleneck of low signal to noise ratio and sensitivity, it needs further improvement in fluorescent probe design and understanding of tumor development process. Recent reports reveal that lysosome's acidity in cancer cells can be below 4.5 with high Na+ /H+ exchange activity, which makes it an ideal target intracellular organelle for cancer diagnosis based on the variation of pH. Herein, a boron 2-(2'-pyridyl) imidazole complex derivative (BOPIM-N) is developed, with the ability to show a pH-activatable "OFF-ON" fluorescent switch by inhibiting twisted intramolecular charge transfer upon protonation at pH 3.8-4.5, which is studied for its selective viable cancer cell imaging ability in both in vitro and in vivo experiments. Interestingly, BOPIM-N can specifically emit green fluorescence in lysosomes of cancer cells, indicating its promising cancer cell specific imaging ability. More importantly, nanoformulated BOPIM-N probes can be specifically light-ON in tumor bearing site of nude mice with resolution up to cellular level, indicating its potential application in tumor diagnosis and precision medicine.
Asunto(s)
Imidazoles/química , Lisosomas/química , Sondas Moleculares/química , Polímeros/química , Animales , Línea Celular Tumoral , Humanos , Concentración de Iones de Hidrógeno , Ratones , Ratones Desnudos , Imagen Óptica/métodosRESUMEN
A gold nanotip array platform with a combination of ultrasensitive electrochemical sensing and spectroscopic monitoring capability is reported. Adenosine triphosphate is detected down to 1 pM according to the impedance changes in response to aptamer-specific binding. Furthermore, the local molecular information can be monitored at the individual plasmonic nanotips, and hence provide the capability for a better understanding of complex biological processes.
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Técnicas Electroquímicas/instrumentación , Oro/química , Nanotecnología/instrumentación , Espectrometría Raman , Adenosina Trifosfato/análisis , ADN/química , Dimetilpolisiloxanos/química , Azul de Metileno/químicaRESUMEN
Biodegradable piezoelectric force sensors can be used as implantable medical devices for monitoring physiological pressures of impaired organs or providing essential stimuli for drug delivery and tissue regeneration without the need of additional invasive removal surgery or battery power. However, traditional piezoelectric materials, such as inorganic ceramics and organic polymers, show unsatisfactory degradability, and cytotoxicity. Amino acid crystals are biocompatible and exhibit outstanding piezoelectric properties, but their small crystal size makes it difficult to align the crystals for practical applications. Here, a mechanical-annealing strategy is reported for engineering all-organic biodegradable piezoelectric force sensors using natural amino acid crystals as piezoelectric materials. It is shown that the piezoelectric constant of the mechanical-annealed crystals can reach 12 times that of the single crystal powders. Moreover, mechanical annealing results in flat and smooth surfaces, thus improving the contact of the crystal films with the electrodes and leading to high output voltages of the devices. The packaged force sensors can be used to monitor dynamic motions, including muscle contraction and lung respiration, in vivo for 4 weeks and then gradually degrade without causing obvious inflammation or systemic toxicity. This work provides a way to engineer all-organic and biodegradable force sensors for potential clinical applications.
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Aminoácidos , Fenómenos Mecánicos , Prótesis e Implantes , Ingeniería , PolímerosRESUMEN
Poly(ε-lysine) (ε-PL)-analogous click polypeptides with not only similar α-amino side groups but also similar main chain to ε-PL were chemically synthesized for the first time through click polymerization from aspartic (or glutamic)-acid-based dialkyne and diazide monomers. With microwave-assisting, the reaction time of click polymerization was compressed into 30 min. The polymers were fully characterized by NMR, ATR-FTIR, and SEC-MALLS analysis. The deprotected click polypeptides had similar pK(a) value (7.5) and relatively low cytotoxicity as ε-PL and could be used as substitutes of ε-PL in biomedical applications, especially in endotoxin selective removal. Poly(ethylene glycol) (PEG)-containing alternating copolymers with α-amino groups were also synthesized and characterized. After deprotection, the polymers could be used as functional gene vector with PEG shadowing system and NCA initiator to get amphiphilic graft polymers.
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Microondas , Polilisina/síntesis química , Polímeros/síntesis química , Aminoácidos , Endotoxinas/aislamiento & purificación , Humanos , Polietilenglicoles , Polilisina/uso terapéutico , Polimerizacion , Polímeros/uso terapéuticoRESUMEN
Simultaneous implementation of high signal-to-noise ratio (SNR) but low crosstalk is of great importance for weak surface electromyography (sEMG) signals when precisely driving a prosthesis to perform sophisticated activities. However, due to gaps with the curved skin during muscle contraction, many electrodes have poor compliance with skin and suffer from high bioelectrical impedance. This causes serious noise and error in the signals, especially the signals from low-level muscle contractions. Here, the design of a compliant electrode based on an adhesive hydrogel, alginate-polyacrylamide (Alg-PAAm) is reported, which eliminates those large gaps through the strong electrostatic interaction and abundant hydrogen bond with the skin. The obtained compliant electrode, having an ultralow bioelectrical impedance of ≈20 kΩ, can monitor even 2.1% maximal voluntary contraction (MVC) of muscle. Furthermore, benefiting from the high SNR of >5:1 at low-level MVC, the crosstalk from irrelevant muscle is minimized through reducing the electrode size. Finally, a prosthesis is successfully demonstrated to precisely grasp a needle based on a 9 mm2 Alg-PAAm compliant electrode. The strategy to design such compliant electrodes provides the potential for improving the quality of dynamically weak sEMG signals to precisely control prosthesis in performing purposefully dexterous activity.
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Hidrogeles/química , Resinas Acrílicas/química , Adhesividad , Alginatos/química , Impedancia Eléctrica , ElectrodosRESUMEN
Bacterial infections remain a leading threat to global health because of the misuse of antibiotics and the rise in drug-resistant pathogens. Although several strategies such as photothermal therapy and magneto-thermal therapy can suppress bacterial infections, excessive heat often damages host cells and lengthens the healing time. Here, a localized thermal managing strategy, thermal-disrupting interface induced mitigation (TRIM), is reported, to minimize intercellular cohesion loss for accurate antibacterial therapy. The TRIM dressing film is composed of alternative microscale arrangement of heat-responsive hydrogel regions and mechanical support regions, which enables the surface microtopography to have a significant effect on disrupting bacterial colonization upon infrared irradiation. The regulation of the interfacial contact to the attached skin confines the produced heat and minimizes the risk of skin damage during thermoablation. Quantitative mechanobiology studies demonstrate the TRIM dressing film with a critical dimension for surface features plays a critical role in maintaining intercellular cohesion of the epidermis during photothermal therapy. Finally, endowing wound dressing with the TRIM effect via in vivo studies in S. aureus infected mice demonstrates a promising strategy for mitigating the side effects of photothermal therapy against a wide spectrum of bacterial infections, promoting future biointerface design for antibacterial therapy.
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Antibacterianos/química , Fototerapia , Infecciones Estafilocócicas/terapia , Resinas Acrílicas/química , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Vendajes , Oro/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/efectos de la radiación , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/efectos de la radiación , Hidrogeles/química , Rayos Infrarrojos/uso terapéutico , Nanopartículas del Metal/química , Ratones , Infecciones Estafilocócicas/patología , Infecciones Estafilocócicas/veterinariaRESUMEN
The reciprocal mechanical interaction of engineered materials with biointerfaces have long been observed and exploited in biomedical applications. It contributes to the rise of biomechano-responsive materials and biomechano-stimulatory materials, constituting the biomechano-interactive interfaces. Here, endogenous and exogenous biomechanical stimuli available for mechanoresponsive interfaces are briefed and their mechanistic responses, including deformation and volume change, mechanomanipulation of physical and chemical bonds, dissociation of assemblies, and coupling with thermoresponsiveness are summarized. The mechanostimulatory materials, however, are capable of delivering mechanical cues, including stiffness, viscoelasticity, geometrical constraints, and mechanical loads, to modulate physiological and pathological behaviors of living tissues through the adaptive cellular mechanotransduction. The biomechano-interactive materials and interfaces are widely implemented in such fields as mechanotriggered therapeutics and diagnosis, adaptive biophysical sensors, biointegrated soft actuators, and mechanorobust tissue engineering, which have offered unprecedented opportunities for precision and personalized medicine. Pending challenges are also addressed to shed a light on future advances with respect to translational implementations.
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Materiales Biocompatibles/química , Animales , Portadores de Fármacos/química , Elasticidad , Mecanotransducción Celular , Nanopartículas/química , Ingeniería de TejidosRESUMEN
Soft and stretchable electronic devices are important in wearable and implantable applications because of the high skin conformability. Due to the natural biocompatibility and biodegradability, silk protein is one of the ideal platforms for wearable electronic devices. However, the realization of skin-conformable electronic devices based on silk has been limited by the mechanical mismatch with skin, and the difficulty in integrating stretchable electronics. Here, silk protein is used as the substrate for soft and stretchable on-skin electronics. The original high Young's modulus (5-12 GPa) and low stretchability (<20%) are tuned into 0.1-2 MPa and > 400%, respectively. This plasticization is realized by the addition of CaCl2 and ambient hydration, whose mechanism is further investigated by molecular dynamics simulations. Moreover, highly stretchable (>100%) electrodes are obtained by the thin-film metallization and the formation of wrinkled structures after ambient hydration. Finally, the plasticized silk electrodes, with the high electrical performance and skin conformability, achieve on-skin electrophysiological recording comparable to that by commercial gel electrodes. The proposed skin-conformable electronics based on biomaterials will pave the way for the harmonized integration of electronics into human.
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Seda , Materiales Biocompatibles , Módulo de Elasticidad , Electrodos , Humanos , PielRESUMEN
The spatial-temporal synchronization of photothermal therapy and chemotherapy is highly desirable for an efficient cancer treatment with synergistic effect. Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained nanoparticles (NPs) exhibit good monodispersity and excellent stability, which can efficiently convert laser energy into thermal energy for photothermal therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2-naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR two-photon laser irradiation, which leads to fast drug release. Furthermore, the surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD) tripeptide significantly enhances the accumulation of the NPs within integrin αvß3 overexpressed cancer cells. The half-maximal inhibitory concentration (IC50) of the combination therapy is 13.7 µg mL(-1), while the IC50 for chemotherapy and photothermal therapy alone is 147.8 µg mL(-1) and 36.2 µg mL(-1), respectively. The combination index (C.I.) is 0.48 (<1), which indicates the synergistic effect for chemotherapy and PTT. These findings provide an excellent NIR laser regulated nanoplatform for combined cancer treatment with synergistic effect due to the synchronous chemo- and photo-thermal therapy.
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Antineoplásicos/química , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos , Ácido Láctico/química , Naftoquinonas/química , Neoplasias/tratamiento farmacológico , Polímeros/química , Línea Celular Tumoral , Núcleo Celular/metabolismo , Terapia Combinada , Portadores de Fármacos/administración & dosificación , Femenino , Células HEK293 , Humanos , Hipertermia Inducida , Concentración 50 Inhibidora , Integrina alfaVbeta3/química , Rayos Láser , Células MCF-7 , Espectroscopía de Resonancia Magnética , Microscopía Confocal , Nanopartículas/química , Nanotecnología , Oligopéptidos/química , Fotoquimioterapia , Fotones , Poliésteres , Espectroscopía Infrarroja CortaRESUMEN
Programmable polymer substrates, which mimic the variable extracellular matrices in living systems, are used to regulate multicellular morphology, via orthogonally modulating the matrix topography and elasticity. The multicellular morphology is dependent on the competition between cell-matrix adhesion and cell-cell adhesion. Decreasing the cell-matrix adhesion provokes cytoskeleton reorganization, inhibits lamellipodial crawling, and thus enhances the leakiness of multicellular morphology.