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1.
Long blood circulation in vivo remains a challenge to dual‐drug‐loaded nanocarriers for synergistic chemotherapy. Herein, a novel strategy to prepare lollipop‐like dual‐drug‐loaded nanoparticles (DOX–PDA–gossypol NPs) is developed based on the self‐assembly of gossypol, doxorubicin (DOX), and polydopamine (PDA) via π–π stacking. Dopamine polymerizes to PDA and fills the gaps between the gossypol and DOX molecules to form the super compact long‐circulating nanoparticles. The DOX–PDA–gossypol NPs show a suitable particle size of 59.6 ± 9.6 nm, high drug loading of 91%, superb stability, high maximum‐tolerated dose (MTD) of over 60 mg kg‐1, and negligible toxicity. These NPs also exhibit pH‐dependent drug release and low combination index (0.23). Notably, they show dramatically ultralong blood circulation (>192 h) with elimination half times 458‐fold and 258‐fold longer than that of free DOX and free gossypol, respectively. These values are markedly higher than most of the reported results. Therefore, the DOX–PDA–gossypol NPs have a high tumor accumulation of 12% remaining on the 8th day postinjection. This characteristic contributes to the excellent tumor comprehensive synergistic therapeutic efficacy (TIR > 90%) with low administration dosage and is benefitted for widening the drug therapeutic window. Thus, the proposed strategy has remarkable potential for tumor synergistic therapy.  相似文献   

2.
Poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) nanoparticles, after being coated with polyethylene glycol (PEG), are used as a drug carrier to load various types of aromatic therapeutic molecules, including chemotherapy drugs doxorubicin (DOX) and SN38, as well as a photodynamic agent chlorin e6 (Ce6), through ππ stacking and hydrophobic interaction. Interesting functionalities of PEDOT:PSS‐PEG as an unique versatile drug delivery platform are discovered. Firstly, for water‐insoluble drugs such as SN38, the loading on PEDOT:PSS‐PEG dramatically enhances its water solubility, while maintaining its cytotoxicity to cancer cells. Secondly, the delivery of Ce6 by PEDOT:PSS‐PEG is able to remarkably accelerate the cellular uptake of Ce6 molecules, and thus offers improved photodynamic therapeutic efficacy. Using DOX‐loaded PEDOT:PSS‐PEG as the model system, it is demonstrated that the photothermal effect of PEDOT:PSS‐PEG can be utilized to promote the delivery of this chemotherapeutic agent, achieving a combined photothermal‐ and chemotherapy with an obvious synergistic cancer killing effect. Moreover, it is also shown that multiple types of therapeutic agents could be simultaneously loaded on PEDOT:PSS‐PEG nanoparticles and delivered into cancer cells. This work highlights the great potential of NIR‐absorbing polymeric nanoparticles as multifunctional drug carriers for potential cancer combination therapy with high efficacy.  相似文献   

3.
Although near‐infrared (NIR) light‐absorbing organic dyes have recently been proposed for photothermal ablation of tumors, their clinical applications have often been hampered by problems such as low water solubility and minimal tissue absorption. Rapid development of nanotechnology provides various novel nanostructures to address these issues. In this work, doxorubicin (DOX)‐loaded stealth liposomes are engineered through the incorporation of an NIR‐absorptive heptamethine indocyanine dye IR825 into the thermoresponsive liposomes for photothermal/chemo combined cancer therapy. It is demonstrated that the lipid nanostructure can enhance the bioavailability of water‐insoluble IR825 for efficient photothermal treatment, while delivering the anticancer drug doxorubicin to achieve simultaneous anticancer medication. The combined treatment of photothermal ablation and chemotherapy synergistically improves the overall cancer cell killing efficiency, which can be of future clinical interest.  相似文献   

4.
Photodynamic therapy (PDT) mediated by near‐infrared (NIR) dyes is a promising cancer treatment modality; however, its use is limited by significant challenges, such as hypoxic tumor microenvironments and self‐quenching of photosensitizers. These challenges hamper its utility in inducing immunogenic cell death (ICD) and triggering potent systemic antitumor immune responses. This study demonstrates that molecular dispersion of NIR dyes in nanocarriers can significantly enhance their ability to produce reactive oxygen species and potentiate synergistic PDT and photothermal therapy against tumors. Specifically, NIR dye indocyanine green (ICG) can be spontaneously adsorbed to covalent organic frameworks (COFs) via π–π conjugations to prevent intermolecular stacking interactions. Then, ICG‐loaded COFs are ultrasonically exfoliated and coated with polydopamine (PDA) to construct a new phototherapeutic agent ICG@COF‐1@PDA with enhanced efficacy. In conjunction with ICG@COF‐1@PDA, a single round of NIR laser irradiation can induce obvious ICD, elicit antitumor immunity in colorectal cancer, and yield 62.9% inhibition of untreated distant tumors. ICG@COF‐1@PDA also exhibits notable phototherapeutic efficacy against 4T1 murine breast to lung metastasis, a spontaneous metastasis mode for triple‐negative breast cancers (TNBCs). Overall, this study reveals a novel nanodelivery system for molecular dispersion of NIR dyes, which may present new therapeutic opportunities against primary and metastatic tumors.  相似文献   

5.
The integration of efficient imaging for diagnosis and synergistic tumor therapy into a single‐component nanoplatform is much promising for high efficacy tumor treatment but still in a great challenge. Herein, a smart and versatile nanotheranostic platform based on hollow mesoporous Prussian blue nanoparticles (HMPBs) with perfluoropentane (PFP) and doxorubicin (DOX) inside, has been designed, for the first time, to achieve the distinct in vivo synergistic chemo‐thermal tumor therapy and synchronous diagnosis and monitoring by ultrasound (US)/photoacoustic (PA) dual mode imaging. The prepared HMPBs show excellent photothermal conversion properties with large molar extinction coefficient (≈1.2 × 1011m ?1 cm?1) and extremely high photothermal conversion efficiency (41.4%). Such a novel theranostic nanoplatform is expected to overcome the inevitable tumor recurrence and metastasis resulting from the inhomogeneous ablation of single thermal therapy, which will find a promising prospect in the application of noninvasive cancer therapy.  相似文献   

6.
Core/shell nanoparticles that display a pH‐sensitive thermal response, self‐assembled from the amphiphilic tercopolymer, poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide‐co‐10‐undecenoic acid) (P(NIPAAm‐co‐DMAAm‐co‐UA)), have recently been reported. In this study, folic acid is conjugated to the hydrophilic segment of the polymer through the free amine group (for targeting cancer cells that overexpress folate receptors) and cholesterol is grafted to the hydrophobic segment of the polymer. This polymer also self‐assembles into core/shell nanoparticles that exhibit pH‐induced temperature sensitivity, but they possess a more stable hydrophobic core than the original polymer P(NIPAAm‐co‐DMAAm‐co‐UA) and a shell containing folate molecules. An anticancer drug, doxorubicin (DOX), is encapsulated into the nanoparticles. DOX release is also pH‐dependent. DOX molecules delivered by P(NIPAAm‐co‐DMAAm‐co‐UA) and folate‐conjugated P(NIPAAm‐co‐DMAAm‐co‐UA)‐g‐cholesterol nanoparticles enter the nucleus more rapidly than those transported by P(NIPAAm‐co‐DMAAm)‐b‐poly(lactide‐co‐glycolide) nanoparticles, which are not pH sensitive. More importantly, these nanoparticles can recognize folate‐receptor‐expressing cancer cells. Compared to the nanoparticles without folate, the DOX‐loaded nanoparticles with folate yield a greater cellular uptake because of the folate‐receptor‐mediated endocytosis process, and, thus, higher cytotoxicity results. These multifunctional polymer core/shell nanoparticles may make a promising carrier to target drugs to cancer cells and release the drug molecules to the cytoplasm inside the cells.  相似文献   

7.
A high‐performance naphthalene diimide (NDI)‐based conjugated polymer for use as the active layer of n‐channel organic field‐effect transistors (OFETs) is reported. The solution‐processable n‐channel polymer is systematically designed and synthesized with an alternating structure of long alkyl substituted‐NDI and thienylene–vinylene–thienylene units (PNDI‐TVT). The material has a well‐controlled molecular structure with an extended π‐conjugated backbone, with no increase in the LUMO level, achieving a high mobility and highly ambient stable n‐type OFET. The top‐gate, bottom‐contact device shows remarkably high electron charge‐carrier mobility of up to 1.8 cm2 V?1 s?1 (Ion/Ioff = 106) with the commonly used polymer dielectric, poly(methyl methacrylate) (PMMA). Moreover, PNDI‐TVT OFETs exhibit excellent air and operation stability. Such high device performance is attributed to improved π–π intermolecular interactions owing to the extended π‐conjugation, apart from the improved crystallinity and highly interdigitated lamellar structure caused by the extended π–π backbone and long alkyl groups.  相似文献   

8.
Fabricating theranostic nanoparticles combining multimode disease diagnosis and therapeutic has become an emerging approach for personal nanomedicine. However, the diagnostic capability, biocompatibility, and therapeutic efficiency of theranostic nanoplatforms limit their clinic widespread applications. Targeting to the theme of accurate diagnosis and effective therapy of cancer cells, a multifunctional nanoplatform of aptamer and polyethylene glycol (PEG) conjugated MoS2 nanosheets decorated with Cu1.8S nanoparticles (ATPMC) is developed. The ATPMC nanoplatform accomplishes photoluminescence imaging, photoacoustic imaging, and photothermal imaging for in vitro and in vivo tumor cells imaging diagnosis. Meanwhile, the ATPMC nanoplatform facilitates selective delivery of gene probe to detect intracellular microRNA aberrantly expressed in cancer cells and anticancer drug doxorubicin (DOX) for chemotherapy. Moreover, the synergistic interaction of MoS2 and Cu1.8S renders the ATPMC nanoplatform with superb photothermal conversion efficiency. The ATPMC nanoplatform loaded with DOX displays near‐infrared laser‐induced programmed chemotherapy and advanced photothermal therapy, and the targeted chemo‐photothermal therapy presents excellent antitumor efficiency.  相似文献   

9.
In this study, biocompatible Fe(III) species‐WS2‐polyvinylpyrrolidone (Fe(III) @ WS2‐PVP) nanocapsules with enhanced biodegradability and doxorubicin (DOX) loading capacity are one‐pot synthesized. In this nanocapsule, there exists a redox reaction between Fe(III) species and WS2 to form Fe2+ and WO42?. The formed Fe2+ could be oxidized to Fe3+, which reacts with Fe(III) @ WS2‐PVP again to continuously produce Fe2+ and WO42?. Such a repeated endogenous redox reaction leads to an enhanced biodegradation and DOX release of DOX @ Fe(III) @ WS2‐PVP. More strikingly, the Fe2+ generation and DOX release are further accelerated by the overexpressed H2O2 and the mild acidic tumor microenvironment (TME), since H2O2 and H+ can accelerate the oxidation of Fe2+. The continuously generated Fe2+ catalyzes a fast Fenton reaction with the innate H2O2 in tumor cells and produces abundant highly toxic hydroxyl radicals for nanocatalytic tumor therapy. Together with the high photothermal transforming capability, the DOX @ Fe(III) @WS2‐PVP nanocapsules successfully achieve the endogenous redox reaction and exogenous TME‐augmented tumor photothermal therapy, chemo and nanocatalytic therapy outcome. The concept of material design can be innovatively extended to the synthesis of biodegradable Fe(III) @ MoS2‐PVP nanocomposite, thus paving a promising novel way for the rational design of intelligent theranostic agents for highly efficient treatment of cancer.  相似文献   

10.
In this work, a joint experimental and computational study on the synthesis, self‐assembly, and ionic conduction characteristics of a new conjugated liquid crystal quaterthiophene/poly(ethylene oxide) (PEO4) consisting of terminal tetraethyleneglycol monomethyl ether groups on both ends of a quaterthiophene core is performed. In agreement with molecular dynamic simulations, temperature‐dependent grazing‐incidence wide angle X‐ray scattering and X‐ray diffraction indicate that the molecule spontaneously forms a smectic phase at ambient temperature as characterized both in bulk and thin film configurations. Significantly, this smectic phase is maintained upon blending with bis(trifluoro‐methanesulfonyl)imide as ion source at a concentration ratio up to r = [Li+]/[EO] = 0.05. Nanosegregation between oligothiophene and PEO moieties and π–π stacking of thiophene rings lead to the formation of efficient 2D pathways for ion transport, resulting in thin‐film in‐plane ionic conductivity as high as 5.2 × 10?4 S cm?1 at 70 °C and r = 0.05 as measured by electrochemical impedance spectroscopy. Upon heating the samples above a transition temperature around 95 °C, an isotropic phase forms associated with a pronounced drop in ionic conductivity. Upon cooling, partial and local reordering of the conducting smectic domains leads to an ionic conductivity decrease compared to the as‐cast state.  相似文献   

11.
Tumor hypoxia strengthens tumor resistance to different therapies especially oxygen involved strategies, such as photodynamic therapy (PDT). Herein, the thermal responsive phase change materials (PCM) are utilized to coencapsulate ultrasmall manganese dioxide (sMnO2) and organic photosensitizer IR780 to obtain IR780‐sMnO2‐PCM nanoparticles for controlled tumor hypoxia modulation and enhanced phototherapy. The thermal responsive protective PCM layer can not only prevent IR780 from photodegradation, but also immediately release sMnO2 to decompose endogenous H2O2 and generate enough oxygen for PDT under laser irradiation. Owing to the efficient accumulation of IR780‐sMnO2‐PCM nanoparticles in tumor under intravenous injection as revealed by both florescence imaging and photoacoustic imaging, the tumor hypoxia is greatly relieved. Furthermore, in vivo combined photothermal therapy (PTT) and PDT, IR780‐sMnO2‐PCM nanoparticles, compared to IR780‐PCM nanoparticles, exhibit better performance in inhibiting tumor growth. The results highlight the promise of IR780‐sMnO2‐PCM in controlled modulation of tumor hypoxia to overcome current limitations of cancer therapies.  相似文献   

12.
The multidrug resistance (MDR) of cancer cells is a major obstacle in cancer chemotherapy and very few strategies are available to overcome it. Here, a new strategy is developed to codeliver a π–π stacked dual anticancer drug combination with an actively targeted, pH‐ and reduction‐sensitive polymer micellar platform for combating multidrug resistance and tumor metastasis. In contrast to other methods, two traditional chemotherapeutics, doxorubicin (DOX) and 10‐hydroxycamptothecin with complex aromatic π–π conjugated structures, are integrated into one drug delivery system via a π–π stacking interaction, which enables the released drugs to evade the recognition of drug pumps due to a slight change in the drug's molecular structure. The micelles exhibit active targeting of DOX‐resistant human breast cancer MCF‐7 cells (MCF‐7/ADR) and have the ability to control the release of the drug in response to the microenvironmental stimuli of tumor cells. As a result, the codelivery of the π–π stacked dual anticancer drug combination displays high therapeutic efficacy in the MCF‐7/ADR tumor model and successfully prevents the lung metastasis of tumor cells. The mechanism underlying the reversal of MDR is investigated, and the results reveal that the synergistic effect of the π–π stacked dual drugs promotes mitochondria‐dependent apoptosis.  相似文献   

13.
Development of single near‐infrared (NIR) laser triggered phototheranostics for multimodal imaging guided combination therapy is highly desirable but is still a big challenge. Herein, a novel small‐molecule dye DPP‐BT is designed and synthesized, which shows strong absorption in the first NIR window (NIR‐I) and fluorescence emission in the second NIR region (NIR‐II). Such a dye not only acts as a dual‐modal contrast agent for NIR‐II fluorescence and photoacoustic (PA) imaging, but also serves as a combined therapeutic agent for photothermal therapy (PTT) and photodynamic therapy (PDT). The single NIR laser triggered all‐in‐one phototheranostic nanoparticles are constructed by encapsulating the dye DPP‐BT, chemotherapy drug DOX, and natural phase‐change materials with a folic acid functionalized amphiphile. Notably, under NIR laser irradiation, DOX can effectively release from such nanoparticles via NIR‐induced hyperthermia of DPP‐BT. By intravenous injection of such nanoparticles into Hela tumor‐bearing mice, the tumor size and location can be accurately observed via NIR‐II fluorescence/PA dual‐modal imaging. From in vitro and in vivo therapy results, such nanoparticles simultaneously present remarkable antitumor efficacy by PTT/PDT/chemo combination therapy, which is triggered by a single NIR laser. Overall, this work provides an innovative strategy to design and construct all‐in‐one nanoplatforms for clinical phototheranostics.  相似文献   

14.
The discovery of nanodipolar π‐conjugated oligomer‐containing polymers as high performance nanodielectric materials with high permittivity and low dielectric loss over a wide range of frequency (100 Hz–4 MHz) is reported. Terthiophene‐containing methacrylate polymers are synthesized by reversible addition fragmentation transfer (RAFT) polymerization. Both X‐ray and thermal studies indicate the formation of small crystalline domains of terthiophene side chains dispersed in amorphous matrix. The highly polarizable and fast‐responsive nanodipoles from the nanoscale crystalline domains (<2 nm) are believed to dictate the performance. These polymers uniquely satisfy nanodipole architectures conjectured two decades ago to guide the design of high performance nanodielectric materials. This unprecedented approach can be generalized to a variety of π‐conjugated oligomer‐containing polymers for the development of high energy density capacitor materials.  相似文献   

15.
Recently, polymer field‐effect transistors have gone through rapid development. Nevertheless, charge transport mechanism and structure‐property relationship are less understood. Here we use strong electron‐deficient benzodifurandione‐based poly(p‐phenylene vinylene) ( BDPPV ) as polymer backbone and develop six BDPPV ‐based polymers ( BDPPV‐C1 to C6 ) with various side‐chain branching positions to systematically study the side‐chain effect on device performance. All the polymers exhibited ambient‐stable n‐type transporting behaviors with the highest electron mobility of up to 1.40 cm2 V?1 s?1. The film morphologies and microstructures of all the six polymers were systematically investigated. Our results demonstrate that the interchain π–π stacking distance decreases as moving the branching position away from polymer backbones, and an unprecedentedly close π–π stacking distance down to 3.38 Å is obtained for BDPPV‐C4 to C6 . Nonetheless, closer π–π stacking distance does not always correlate with higher electron mobility. Polymer crystallinity, thin film disorder, and polymer packing conformation, which all influenced by side‐chain branching position, are proved to show significant influence on device performance. Our study not only reveals that π–π stacking distance is not the decisive factor on carrier mobility in conjugated polymers but also demonstrates that side‐chain branching position engineering is a powerful strategy to modulate and balance these factors in conjugated polymers.  相似文献   

16.
A donor–acceptor (D–A) semiconducting copolymer, PDPP‐TVT‐29, comprising a diketopyrrolopyrrole (DPP) derivative with long, linear, space‐separated alkyl side‐chains and thiophene vinylene thiophene (TVT) for organic field‐effect transistors (OFETs) can form highly π‐conjugated structures with an edge‐on molecular orientation in an as‐spun film. In particular, the layer‐like conjugated film morphologies can be developed via short‐term thermal annealing above 150 °C for 10 min. The strong intermolecular interaction, originating from the fused DPP and D–A interaction, leads to the spontaneous self‐assembly of polymer chains within close proximity (with π‐overlap distance of 3.55 Å) and forms unexpectedly long‐range π‐conjugation, which is favorable for both intra‐ and intermolecular charge transport. Unlike intergranular nanorods in the as‐spun film, well‐conjugated layers in the 200 °C‐annealed film can yield more efficient charge‐transport pathways. The granular morphology of the as‐spun PDPP‐TVT‐29 film produces a field‐effect mobility (μ FET) of 1.39 cm2 V?1 s?1 in an OFET based on a polymer‐treated SiO2 dielectric, while the 27‐Å‐step layered morphology in the 200 °C‐annealed films shows high μ FET values of up to 3.7 cm2 V?1 s?1.  相似文献   

17.
Protein‐based theranostic agents (PBTAs) exhibit superior performance in the diagnosis and therapy of cancers. However, the in vivo applications of PBTA are largely limited by undesired accumulation, penetration, or selectivity. Here, an ATP‐supersensitive protein cluster is fabricated for promoting PBTA delivery and enhancing magnetic resonance imaging (MRI)‐guided tumor photothermal therapy. Gd3+‐ and CuS‐coloaded small bovine serum albumin nanoparticles (GdCuB) are synthesized as the model protein with a size of 9 nm and are encapsulated into charge switchable polycations (DEP) to form DEP/GdCuB nanoclusters of 120 nm. In blood circulation, DEP/GdCuB significantly extends the half‐lifetime and thereby enhances the tumor accumulation of GdCuB. When the clusters reach the tumor site, the extracellular adenosine triphosphate (ATP) can effectively trigger the release of GdCuB, resulting in tumoral deep penetration as well as the activation of T1‐weighted MRI (r1 value switched from 2.8 × 10?3 to 11.8 × 10?3 m ?1 s?1). Furthermore, this delivery strategy also improves the tumoral photothermal therapy efficacy with the MRI‐guided therapy. The study of ATP‐activated nanoclusters develops a novel strategy for tumor deep penetration and on/off imaging of PBTA by size switchable technology, and reveals the potential for MRI‐guided therapy of cancers.  相似文献   

18.
High‐security nanoplatform with enhanced therapy compliance is extremely promising for tumor. Herein, using a simple and high‐efficient self‐assembly method, a novel active‐targeting nanocluster probe, namely, Ag2S/chlorin e6 (Ce6)/DOX@DSPE‐mPEG2000‐folate (ACD‐FA) is synthesized. Experiments indicate that ACD‐FA is capable of specifically labeling tumor and guiding targeting ablation of the tumor via precise positioning from fluorescence and photoacoustic imaging. Importantly, the probe is endowed with a photodynamic “on‐off” effect, that is, Ag2S could effectively quench the fluorescence of chlorin e6 (89.5%) and inhibit release of 1O2 (92.7%), which is conducive to avoid unwanted phototoxicity during transhipment in the body, and only after nanocluster endocytosed by tumor cells could release Ce6 to produce 1O2. Moreover, ACD‐FA also achieves excellent acid‐responsive drug release, and exhibits eminent chemo‐photothermal and photodynamic effects upon laser irradiation. Compared with single or two treatment combining modalities, ACD‐FA could provide the best cancer therapeutic effect with a relatively low dose, because it made the most of combined effect from chemo‐photothermal and controlled photodynamic therapy, and significantly improves the drug compliance. Besides, the active‐targeting nanocluster notably reduces nonspecific toxicity of both doxorubicin and chlorin e6. Together, this study demonstrates the potency of a newly designed nanocluster for nonradioactive concomitant therapy with precise tumor‐targeting capability.  相似文献   

19.
20.
The synthesis of two cyan color (blue and green emission) displaying high molecular weight 2,6‐bis(pyrazolyl)pyridine‐co‐octylated phenylethynyl conjugated polymers (CPs) is presented. The conjugated polymers are solution‐processed to prepare spin coated thin films and self‐assembled nano/microscale spheres, exhibiting cyan color under UV. Additionally, the metal coordinating ability of the 2,6‐bis(pyrazolyl)pyridine available on the surface of the CP films and spheres is exploited to prepare red emitting Eu(III) metal ion containing conjugated polymer (MCCP) layer. The fabricated hybrid (CP/MCCP) films and spheres exhibit bright white‐light under UV exposure. The Commission Internationale de l'Eclairage (CIE) coordinates are found to be (x = 0.33, y = 0.37) for hybrid films and (x = 0.30, y = 0.35) for hybrid spheres. These values are almost close to the designated CIE coordinates for ideal white‐light color (x = 0.33, y = 0.33). This easy and efficient fabrication technique to generate white‐color displaying films and nano/microspheres signify an important method in bottom‐up nanotechnology of conjugated polymer based hybrid solid state assemblies.  相似文献   

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