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1.
    
It is of great significance to develop a multifunctional imaging‐guided therapeutic platform with ideal resolution and sensitivity. Notably, rare‐earth (RE) nanoparticles are attractive candidates for multimodal imaging due to their unique optical and magnetic properties. In this work, a rational design of hierarchical nanohybrids employing RE‐Au hetero‐nanostructures is proposed. 1D RE nanorods are adopted as the core to facilitate cellular internalization with the coating of gold nanoshells for photothermal performances. Hydroxyl‐rich polycations with low cytotoxicity are grafted onto the surface of RE‐Au to produce RE‐Au‐PGEA (ethanolamine‐functionalized poly(glycidyl methacrylate)) nanohybrids with impressive gene transfection capability. Given the virtues of all the components, the feasibility of RE‐Au‐PGEA for multifunctional photoacoustic, computed tomography, magnetic resonance, upconversion luminescence imaging, and complementary photothermal therapy/gene therapy therapy is investigated in detail in vitro and in vivo. The visualization of the therapeutic processes with comprehensive information renders RE‐Au‐PGEA nanohybrid an intriguing platform to realize enhanced antitumor efficiency.  相似文献   

2.
    
Integrating multiple mechanisms to maximize photothermal conversion efficiency is a significant strategy but remains challenging to construct therapeutic agents toward photothermal tumor treatment. Here, an approach to synthesize asymmetric Bi2Se3/CdSe-Au hierarchical nanorods with excellent photothermal conversion is reported. Ag wetting-layer is firstly grown to help overcome the interfacial lattice mismatch and promote the site-selective growth of AgCdSe onto one end or side surface of Au nanorods. Subsequently, extraction of Ag+ ions out of lattice is observed during cation exchange reaction and epitaxial growth of Bi2Se3 shell. Bi2Se3/CdSe heterojunction with type-II band alignment is formed and located at the plasmonic hotspots of Au nanorods, which experiences enhanced light absorption and accelerates the charge separation of photo-excited carriers. Under excitation of near-infrared 808 nm laser, the matchstick-like Bi2Se3/CdSe-Au nanorods show an excellent photothermal conversion, with 4.3 times temperature increment ( Δ T) than that of bare Au nanorods. Moreover, in vitro and in vivo experiments verify them as excellent photothermal therapeutic agents.  相似文献   

3.
    
Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the efficient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA‐181b inhibitor (anti‐miR‐181b) is successfully condensed into polyethyleneimine (PEI)‐modified and folate receptor (FR)‐targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti‐miR‐181b/PTPAuNCs nanocomplexes (PTPAuNC‐NPs), which begin with chemical modification of AuNCs with SH‐PEG5000‐folic acid (SH‐PEG5000‐FA) and SH‐PEG5000 through a gold–sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti‐miR‐181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC‐NPs can efficiently deliver anti‐miR‐181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC‐7721 tumor‐bearing nude mice under near‐infrared radiation. All these results suggest that PTPAuNC‐NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.  相似文献   

4.
    
Developing a comprehensive platform which has both diagnosis and therapeutic strategies is necessary for efficient tumor treatment. In this work, a F uel I mproved micro R NA E xplorer (FIRE) probe with signal amplification capability is designed for sensitive detection of microRNA‐21 (miR‐21), which is upregulated in most tumor cells. Besides, FIRE could be loaded by polyethylenimine (PEI)‐modified gold nanorods (AuNR‐PEI) via facile electrostatic interaction, which could avoid the complicated processes commonly used to covalently conjugate nucleic acid probes onto AuNRs. The as‐fabricated AuNR‐PEI/FIRE system could efficiently distinguish tumor cells from non‐tumor cells. The fluorescence signals in MCF‐7 breast carcinoma and HeLa cervical carcinoma cells treated with AuNR‐PEI/FIRE are enhanced 7‐ and 4.5‐fold, respectively, compared with non‐amplification system. AuNR‐PEI/FIRE improves tumor detection ability in vivo and exhibits excellent tumor inhibition efficacy under the fluorescence imaging and photoacoustic imaging guided photothermal therapy. This is the first time to utilize the combined application of amplified nucleic acid detection and photothermal effect derived from gold nanorods together with PA imaging in a facile manner to provide a promising theranostic strategy for accurate diagnosis and tumor therapy.  相似文献   

5.
为了提高信息安全,防止信息泄露,进一步拓宽柔性器件在信息安全领域的应用,本文报道了一种基于双层膜光驱动软体致动器的新型信息示假隐真技术。首先,将所制得的不同长径比的金纳米棒通过图案遮罩和涂覆的方法,均匀地分散到聚丙烯/聚酰亚胺复合薄膜体系中,制得双层膜光热驱动软体致动器,接着将软体致动器进行选择性剪切。当无外界光刺激时,我们把该双层膜所呈现的信息定义为第一种假信息;当外界相应波长的激发光刺激该软体致动器时,该器件由于发生形变可以展示出另外一种信息,我们定义为第二种假信息;由于不同的金纳米棒在相应波长光激发下才具有最高的光热转化效率,因此通过红外相机所观察到的不同区域的温度呈现出一种新的图案,我们定义为真信息,起到信息示假隐真作用。实验结果表明：未接受光照时,软体致动器处于平整状态;在相应波长激光刺激下,被切割部分的软体致动器弯曲角可达到50°以上,裸眼可以清晰地观测所显示信息;而通过红外相机观测到光热区域与非光热区域温度相差至少在10℃以上,可以明显看到所显示的真信息。将软体致动器与信息示假隐真结合在一起,具有新颖性,而且效果明显,为信息安全问题提供了一个新的解决方案。  相似文献   

6.
    
Organic/inorganic nanohybrids hold great importance in fabricating multifunctional theranostics to integrate therapeutic functions with real‐time imaging. Although Au nanorods (NRs) have been employed for theranostics, complicated design of materials limits their practical applications. In this work, new multifunctional theranostic agents are designed and synthesized employing Au NRs with desirable near‐infrared absorbance as the cores. A facile “grafting‐onto” approach is put forward to prepare the series of hierarchical nanohybrids (Au‐PGEA and Au‐PGED) of Au NRs and poly(glycidyl methacrylate)‐based polycations. The resultant nanohybrids can be utilized as gene carriers with high gene transfection performances. The structural effect of polycations on gene transfection is investigated in detail, and Au‐PGEA with abundant hydroxyl groups on the surface exhibits superior performance. Au‐PGEA nanohybrids are further validated to possess remarkable capability of combined photothermal therapy (PTT) and gene therapy (GT) for complementary tumor treatment. Moreover, significantly enhanced computed tomography (CT)/photoacoustic (PA) signals are detected both in vitro and in vivo, verifying the potential of Au‐PGEA for dual‐modal imaging with precise and accurate information. Therefore, these multifunctional nanohybrids fabricated from a simple and straightforward strategy are promising for in vivo dual‐modal CT/PA imaging guided GT/PTT therapy with high antitumor efficacy.  相似文献   

7.
    
The concept of the “supramolecular photothermal effects” refers to the collection property and photothermal conversion efficiency resulting from the supramolecular assembly of molecular photothermal sensitizers. This review considers organic supramolecular photothermal materials assembled at the nanoscale via various molecular self‐assembly strategies and associated with the organization of multiple noncovalent interactions. In these materials, the individual photosensitizer molecules are typically aggregated through self‐assembly in a certain form that exhibits enhanced biostability, increased photothermal conversion efficiency with photoluminescence quenching, and improved photothermal therapeutic effects in comparison with those of the monomeric photosensitizer molecules. These supramolecular photothermal effects are controlled or influenced by intermolecular noncovalent interactions, especially the hydrophobic effects, which are distinct from the mechanisms of conventional sensitizer molecules and polymers and inorganic photothermal agents. A focus lies on how self‐assembly strategies give rise to supramolecular photothermal effects, including polymer and protein fabrication, small molecule self‐assembly, and the construction of donor–acceptor binary systems. Emphases are placed on the rational design of supramolecular photothermal nanomaterials, drug delivery, and in vivo photothermal therapeutic effects. Finally, the key challenges and promising prospects of these supramolecular photothermal nanomaterials in terms of both technical advances and clinical translation are discussed.  相似文献   

8.
    
Near infrared (NIR) light‐activated supersensitive drug release via photothermal conversion is of particular interest due to its advantages in spatial and temporal control. However, such supersensitive drug release is rarely reported for polymeric nanoparticles. In this study, polymeric nanoparticles observed with flowable core can achieve NIR‐activated supersensitive drug release under the assistance of photothermal agent. It is demonstrated that only 5 s NIR irradiation (808 nm, 0.3 W cm?2) leads to 17.8% of doxorubicin (DOX) release, while its release is almost completely stopped when the NIR laser is switched off. In contrast, the control, poly(d ,l ‐lactide) nanoparticles with rigid cores, do not exhibit such supersensitive effect. It is demonstrated that intraparticle temperature is notably increased during photothermal conversion by detecting fluorescein lifetime using a time‐correlated single photon counting (TCSPC) technique, which is the main driving force for such supersensitive drug release from hydrophobic flow core. In contrast, rigid chain of nanoparticular core hinders drug diffusion. Furthermore, such NIR light‐activated supersensitive drug release is demonstrated, which significantly enhances its anticancer efficacy, resulting in overcoming of the resistance of cancer cells against DOX treatment in vitro and in vivo. This simple and highly universal strategy provides a new approach to fabricate NIR light‐activated supersensitive drug delivery systems.  相似文献   

9.
    
Currently, most thrombolytic agents are limited by short circulation time and excessive dose needed for clinical therapy, which increases lethal risk for intracranial hemorrhage. Here, a near‐infrared‐triggered, controlled‐release system, using gold@mesoporous silica core–shell nanospheres (Au@MSNs) with phase‐changed material 1‐tetradecanol, is formulated to release urokinase plasminogen activators (uPA) on demand. The prepared system presents a sensitive system for releasing uPA, owing to an elevated temperature created by Au@MSNs‐induced photothermal effect. For in vitro study, a 3D printed vein vasculature is designed and fabricated to simulate the thrombolysis of system in blood vessel. Murine tail thrombus model is also built to evaluate thrombolysis in vivo. Consequently, localized hyperthermia is validated to possess an effective enhancement for thrombolysis. Therefore, according to the results, the fabricated system demonstrates two aspects of potential superiority: controlled uPA release for reducing risk of side effects, and hyperthermia‐enhanced thrombolysis locally for decreasing drug dosage. Assisted with thermal thrombolysis, the present formulated system shows a high efficiency, on‐demand drug release, and thus a safer protocol for thrombolytic therapy, which fits the developing trends of precision medicine.  相似文献   

10.
    
Up to date, a large variety of liposomal nanodrugs have been explored for cancer nanomedicine, showing encouraging results in both preclinical animal experiments and clinical treatment of cancer patients. Herein, a phospholipid conjugated with a cisplatin prodrug is used as the major structure component of liposomes together with other commercial lipids via self‐assembling. By doping with 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindotricarbocyanine iodide (DiR), a lipophilic dye with strong near infrared (NIR) absorbance and fluorescence, the obtained DiR‐Pt(IV)‐liposome is found to be an effective probe for in vivo NIR fluorescence and photoacoustic bimodal imaging. Attributing to its intrinsically doped cis‐Pt(IV) prodrug, efficient photothermal conversion ability, and excellent tumor homing ability, DiR‐Pt(IV)‐liposome confers greatly enhanced therapeutic outcomes in the combined photothermal‐chemotherapy. Moreover, Pt(IV)‐liposome is also demonstrated to be an efficient carrier for both small hydrophilic molecules and proteins, which are encapsulated inside the water‐cavity of liposomes, further demonstrating the versatile functions of this nanoplatform. This study develops a unique type of liposomal nanomedicine with a prodrug conjugated phospholipid as the major structure component. Such Pt(IV)‐liposome is featured with advantages including precisely defined/easily tunable drug compositions, stealth‐like pharmacokinetics, efficient tumor passive uptake, and the capabilities to simultaneously load with various types of imaging or therapeutic agents.  相似文献   

11.
    
Endometriosis is a prevalent gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, causing chronic pelvic pain, painful periods, and infertility. Despite the common use of hormone therapy and surgical lesion excision in its treatment, there remain significant postoperative risks and potential side effects, with a high recurrence rate. An efficient nonsurgical treatment for this condition is therefore urgently needed. In this study, an interventional hydrogel microsphere with near-infrared (NIR)-controlled curcumin release is developed for the non-invasive thermal therapy of endometriosis. The hydrogel microspheres demonstrate good biocompatibility and photothermal activities, causing the death of endometrial stromal cells under NIR and controlled curcumin (Cur) release. When injected into endometriotic lesions and stimulated by NIR light, the interventional hydrogel microspheres (Cur-FeHMPs) can raise the temperature of the endometriotic lesions to 43.65 °C, inducing endometriotic lesion elimination. Furthermore, the controlled curcumin release from the interventional hydrogel inhibits the proinflammatory environment in endometriosis. The Cur-FeHMPs in combination with NIR present a novel strategy for endometriosis treatment.  相似文献   

12.
    
Gold nanoparticles exhibiting absorption in the desirable near‐infrared region are attractive candidates for photothermal therapy (PTT). Furthermore, the construction of one nanoplatform employing gold nanoparticles for complementary therapy is still a great challenge. Here, well‐defined unique hollow silica nanostars with encapsulated gold caps (starlike Au@SiO2) are readily synthesized using a sacrificial template method. Ethanolamine‐functionalized poly(glycidyl methacrylate) (denoted as BUCT‐PGEA) brushes are then grafted controllably from the surface of starlike Au@SiO2 nanoparticles via surface‐initiated atom transfer radical polymerization to produce starlike Au@SiO2‐PGEA. The photothermal effect of gold caps with a cross cavity can be utilized for PTT. The interior hollow feature of starlike Au@SiO2 nanoparticles endows them with excellent drug loading capability for chemotherapy, while the polycationic BUCT‐PGEA brushes on the surface provide good transfection performances for gene therapy, which will overcome the penetration depth limitation of PTT for tumor therapy. Compared with ordinary spherical Au@SiO2‐PGEA counterparts, the starlike Au@SiO2‐PGEA hybrids with sharp horns favor endocytosis, which can contribute to enhanced antitumor effectiveness. The rational integration of photothermal gold caps, hollow nanostars, and polycations through the facile strategy might offer a promising avenue for complementary cancer therapy.  相似文献   

13.
    
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   

14.
    
The high locoregional breast cancer recurrence rate poses a significant risk for patients' survival. Injecting theranostic drugs‐laden soft tissue‐like hydrogels into the resected breast cavity is a promising strategy to achieve both precisely local therapy of breast cancer and reconstructive mammoplasty. In this work, a robust injectable thermoresponsive supramolecular poly(N‐acryloyl glycinamide‐co‐acrylamide) (PNAm) hydrogel bearing polydopamine (PDA) coated‐gold nanoparticles (AuNPs) and doxorubicin (DOX) is fabricated. The supramolecular polymer nanocomposite (SPN) hydrogels exhibit an excellent photothermal effect arising from PDA‐AuNPs that are tightly fixed to the hydrogel matrix via PDA and amide moieties in the network, built‐in near infrared (NIR) light‐triggered gel–sol transition as well as tunable drug delivery. The PNAm‐PDAAu‐DOX sol driven by prior heating is injected into the cavity of resected cancerous breasts of rats where gelation occurred rapidly while the temperature decreased to body temperature, thereby finely serving as a breast filler. During 4 week of implantation, interval NIR light irradiation can mediate photothermal effect and concertedly controllable DOX release, thus collectively preventing the recurrence of breast cancer. Remarkably, this stable remoldable SPN hydrogel facilitates the breast reconstruction and can be tracked by computed tomography (CT) imaging owing to the intrinsic X‐ray attenuation property of the loaded AuNPs.  相似文献   

15.
    
Optimal nanosized drug delivery systems (NDDS) require long blood circulation and controlled drug release at target lesions for efficient anticancer therapy. Red blood cell (RBC) membrane‐camouflaged nanoparticles (NPs) can integrate flexibility of synergetic materials and highly functionality of RBC membrane, endowed with many unique advantages for drug delivery. Here, new near‐infrared (NIR)‐responsive RBC membrane‐mimetic NPs with NIR‐activated cellular uptake and controlled drug release for treating metastatic breast cancer are reported. An NIR dye is inserted in RBC membrane shells, and the thermoresponsive lipid is employed to the paclitaxel (PTX)‐loaded polymeric cores to fabricate the RBC‐inspired NPs. The fluorescence of dye in the NPs can be used for in vivo tumor imaging with an elongated circulating halftime that is 12.3‐folder higher than that of the free dye. Under the NIR laser stimuli, the tumor cellular uptake of NPs is significantly enhanced to 2.1‐fold higher than that without irradiation. The structure of the RBC‐mimetic NPs can be destroyed by the light‐induced hyperthermia, triggered rapid PTX release (45% in 30 min). These RBC‐mimetic NPs provide a synergetic chemophotothermal therapy, completely inhibited the growth of the primary tumor, and suppress over 98% of lung metastasis in vivo, suggesting it to be an ideal NDDS to fight against metastatic breast cancer.  相似文献   

16.
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17.
    
Carbon‐based nanomaterials have been developed for photothermal cancer therapy, but it is still a great challenge to fabricate their multifunctional counterparts with facile methods, good biocompatibility and dispersity, and high efficiency for cancer theranostics. In this work, an alternative multifunctional nanoplatform is developed based on carbon–silica nanocapsules with gold nanoparticle in the cavity (Au@CSN) for cancer theranostics. The encapsulated chemodrug doxorubicin can be released from the Au@CSN with mesoporous and hollow structure in a near‐infrared light and pH stimuli‐responsive manner, facilitating spatiotemporal therapy to decrease off‐target toxicity. The nanocapsules with efficient photothermal conversion and excellent biocompatibility achieve a synergistic effect of photothermal and chemotherapy. Furthermore, the nanocapsules can act as a multimodal imaging agent of computed tomography and photoacoustic tomography imaging for guiding the therapy. This new design platform can provide a promising strategy for precise cancer theranostics.  相似文献   

18.
Magnetic hyperthermia (MHT) and photothermal therapy (PTT) are emergent state‐of‐the‐art modalities for thermal treatment of cancer. While their mechanisms of action have distinct physical bases, both approaches rely on nanoparticle‐mediated remote onset of thermotherapy. Yet, are the two heating techniques interchangeable? Here, the heating obtained either with MHT or with PTT is compared. The heating is assessed in distinct environments and involves a set of nanomaterials differing in shape (spheres, cubes, stars, shells, and rods) as well as in composition (maghemite, magnetite, cobalt ferrite, and gold). The nanoparticle's heating efficacy in an aqueous medium is first evaluated. Subsequently, the heating efficiency within the cellular environment, where intracellular processing markedly decreases MHT, is compared. Conversely, endosomal sequestration could have a positive effect on PTT. Finally, iron oxide nanocubes and gold nanostars are compared in MHT and PTT in vivo within the heterogeneous intratumoral environment. Overall, two distinct therapeutic approaches, related to high dosage allowing MHT and low dosage associated with PTT, are identified. It is also demonstrated that PTT mediated by magnetic nanoparticles has an efficacy that is comparable to that of plasmonic nanoparticles, but only at significant nanoparticle dosages. At low concentrations, only plasmonic nanoparticles can deliver a therapeutic heating.  相似文献   

19.
    
Nanomedicines that inhibit/disassemble amyloid β (Aβ) aggregates in Alzheimer's disease (AD) are highly desirable yet remain challenging. Therapeutic efficacy and systemic delivery of reported molecules and nanoparticles (NPs) are hampered by various challenges, including low biocompatibility, off‐target toxicity, and lack of specificity. Herein, a versatile NP is designed by integrating high Aβ‐binding affinity, stimuli‐responsive drug release, and photothermal degradation properties for efficient disassembly of Aβ. Near‐infrared (NIR)‐absorbing conjugated polymer PDPP3T‐O14 serves as a photothermal core while thermal‐responsive polymer 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine at the outer layer as the NIR‐stimuli gatekeeper. Curcumin, an inhibitor of Aβ aggregation, is loaded into the NP with high encapsulation efficiency. The 5‐mer β‐sheet breaker peptides LPFFD (Leu‐Pro‐Phe‐Phe‐Asp) having high binding affinity toward Aβ are further anchored onto the surface of polyethylene glycol‐lipid shell for active Aβ‐targeting. The resultant NPs exhibit good Aβ‐targeting ability and obvious photothermal dissociation effect together with Aβ aggregation‐dependent fluorescence detection capability. Upon NIR laser irradiation, entrapped curcumin can be effectively released from the unconsolidated NPs to enhance the anti‐amyloid activity. In vitro studies demonstrate that the NPs dramatically lower Aβ‐induced cytotoxicity of PC12 cells, and therefore show great potential for the application in AD treatment.  相似文献   

20.
血栓是导致心肌梗塞、脑卒中等心血管疾病的主要因素之一。纤维蛋白溶酶类抗血栓药物虽然已被广泛应用于临床, 但依然受到治疗窗口狭窄、半衰期短、易失活和因非靶向性造成的异常出血等不良反应的限制。因此, 有效地将溶栓物质靶向输送到血栓部位并将不良反应降至最低至关重要。基于人血清白蛋白(human serum albumin, HSA) 在血液中的长循环效果和优异的载药特性, 本研究运用基因工程技术在HSA的N末端融合一段能靶向血栓部位的功能肽(P-selectin binding peptide, PBP), 经毕赤酵母表达并纯化得到具有血栓靶向功能的白蛋白融合蛋白。该融合蛋白包载金纳米粒子(gold nanoparticles, Au NPs) 后能够形成均一稳定的纳米粒(PBP-HSA@Au), 粒径为17.7 ± 1.0 nm, zeta电位为-11.3 ± 0.2 mV。细胞毒性和溶血实验证明PBP-HSA@Au生物相容性好, 血小板靶向实验表明PBP的引入赋予了PBP-HSA@Au血栓靶向能力, 近红外光(near infrared ray, NIR) 照射后, PBP-HSA@Au能将光能快速转化为热能进而破坏纤维蛋白, 表现出优异的溶栓效果。本研究设计的白蛋白融合蛋白递送系统为血栓治疗提供了一种精准、快速、非药物的治疗策略, 该体系设计简单、生物相容性高, 具有较强的临床应用性。研究涉及的所有动物实验均按照江南大学动物实验伦理委员会批准的方案执行[JN.No20230915S0301015(423)]。  相似文献   

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