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Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy
摘要： The low tissue penetration depth of external excitation light severely hinders the sensitivity of fluorescence imaging (FL) and the efficacy of photodynamic therapy (PDT) in vivo; thus, rational theranostic platforms that overcome the light penetration depth limit are urgently needed. To overcome this crucial problem, we designed a self-luminescing nanosystem (denoted POCL) with near-infrared (NIR) light emission and singlet oxygen (1O2) generation abilities utilizing an intraparticle relayed resonance energy transfer strategy. Methods: Bis[3,4,6-trichloro-2-(pentyloxycarbonyl) phenyl] oxalate (CPPO) as a chemical energy source with high reactivity toward H2O2, poly[(9,9’-dioctyl-2,7-divinylene-?uorenylene)-alt-2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylene] (PFPV) as a highly efficient chemiluminescence converter, and tetraphenylporphyrin (TPP) as a photosensitizer with NIR emission and 1O2 generation abilities were coencapsulated by self-assembly with poly(ethyleneglycol)-co-poly(caprolactone) (PEG-PCL) and folate-PEG-cholesterol to form the POCL nanoreactor, with folate as the targeting group. A series of in vitro and in vivo analyses, including physical and chemical characterizations, tumor targeting ability, tumor microenvironment activated imaging and photodynamic therapy, as well as biosafety, were systematically investigated to characterize the POCL. Results: The POCL displayed excellent NIR luminescence and 1O2 generation abilities in response to H2O2. Therefore, it could serve as a speci?c H2O2 probe to identify tumors through chemiluminescence imaging and as a chemiluminescence-driven PDT agent for inducing tumor cell apoptosis to inhibit tumor growth due to the abnormal overproduction of H2O2 in the tumor microenvironment. Moreover, the folate ligand on the POCL surface can further improve the accumulation at the tumor site via a receptor-mediated mechanism, thus enhancing tumor imaging and the therapeutic effects both in vitro and in vivo but without any observable systemic toxicity. Conclusion: The nanosystem reported here might serve as a targeted, smart, precise, and noninvasive strategy triggered by the tumor microenvironment rather than by an outside light source for cancer NIR imaging and PDT treatment without limitations on penetration depth.
关键词： chemiluminescent imaging,H2O2,self-luminescing theranostic nanoreactors,intraparticle relayed energy transfer,PDT
更新于2025-09-23 15:23:52
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Antimicrobial-Peptide-Conjugated MoS2 Based Nanoplatform for Multimodal Synergistic Inactivation of Superbugs
摘要： Development of new antibacterial therapeutics material is becoming increasingly urgent due to the huge threat of superbugs, which are responsible for more than half million death each year in this world. Here, we report the development of novel nano-biomaterial based on melittin antimicrobial peptide (AMP) attached transition metal dichalcogenide MoS2 based theranostic nanoplatform. Reported nanoplatform has capability for targeted identification and synergistic inactivation of 100% multidrug-resistant superbugs by combined photo thermal therapy (PTT), photodynamic therapy (PDT) and AMP process. A novel approach for the design of melittin antimicrobial peptide attached MoS2 based nanoplatform is reported, which emits very bright and photo stable fluorescence. It also generates heat as well as reactive oxygen species (ROS) in the presence of 670 nm near infrared light, which allow it to be used as PTT & PDT agent. Due to the presence of AMP, multifunctional AMP exhibits significantly improved antibacterial activity for superbugs via multimodal synergistic killing mechanism. Reported data demonstrate that nanoplatforms are capable of identification of multidrug-resistant superbugs via luminescence imaging. Experimental results show that it is possible to kill only ~45% of superbugs via MoS2 nanopaltform based on PTT & PDT processes together. On the other hand, killing of less than 10% of superbugs is possible using melittin antimicrobial peptide alone. Whereas, 100% Methicillin-resistant Staphylococcus aureus (MRSA), drug resistance Escherichia coli (E. coli) and drug resistance Klebsiella pneumoniae (KPN) superbugs can be killed using antimicrobial peptide attached MoS2 QDs, via synergistic killing mechanism. Mechanisms for possible synergistic killing of multidrug-resistant superbugs have been discussed.
关键词： theranostic transition metal dichalcogenide,photodynamic therapy,multimodal therapy for multidrug-resistant superbugs,Melittin antimicrobial peptide attached MoS2 based nanoplatform,photo thermal therapy
更新于2025-09-23 15:23:52
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Multifunctional Nanotheranostic Gold Nanocages for Photoacoustic Imaging Guided Radio/Photodynamic/Photothermal Synergistic Therapy
摘要： In this work, we developed a novel multifunctional nanoplatform based on hyaluronic acid modified Au nanocages (AuNCs-HA). The rational design of AuNCs-HA renders the nanoplatform three functionalities: (1) AuNCs-HA with excellent LSPR peak in the NIR region act as contrast agent for enhanced photoacoustic (PA) imaging and photothermal therapy (PTT); (2) the nanoplatform with high-energy rays (X-ray) absorption and auger electrons generation acts as a radiosensitizer for radiotherapy; (3) good photocatalytic property and large surface area make AuNCs-HA a photosensitive agent for photodynamic therapy (PDT). In vivo results demonstrated that AuNCs-HA presented excellent PA imaging performance after intravenous injection, which provided contour, size, and location information of the tumor. Moreover, because AuNCs-HA could combine radiotherapy and phototherapy together, the tumors treated with AuNCs-HA showed complete growth inhibition, comparing to that with each therapy alone. Taken together, our present study demonstrates that AuNCs-HA is of great potential as a multifunctional nanoplatform for PA imaging-guided radio- and photo-therapy of tumor.
关键词： PTT,Au nanocages,radiotherapy,PDT,theranostic nanoplatform,PA imaging
更新于2025-09-23 15:21:21
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Enhanced photoacoustic and photothermal effect of functionalized polypyrrole nanoparticles for near-infrared theranostic treatment of tumor
摘要： Functionalized nanomaterials with near-infrared (NIR) responsive capacity are quite promising for theranostic treatment of tumors, but formation of NIR responsive nanomaterials with enhanced theranostic ability and excellent biocompatibility is still very challenging. Herein, PEGylated indocyanine green (ICG)-loaded polypyrrole nanoparticles (PPI NPs) were designed and successfully formed through selecting polydopamine as the linkage between each component, demonstrating enhanced NIR responsive theranostic ability against tumor. Combining in vitro cell study with in vivo assay, the formed PPI NPs were proved being fantastic biocompatible while effectively internalizing in HeLa cells and retaining in HeLa tumor demonstrated by in vitro flow cytometry/confocal measurement and in vivo photoacoustic imaging assay. With the guidance of photoacoustic imaging, successful photothermal ablation of tumor was achieved when treating with PPI NPs plus laser, which was much more effective than the group treated with NPs free of ICG. The greatly combined enhanced photoacoustic and photothermal effect is mainly ascribed to the functionalized polypyrrole nanoparticles, which could accumulate in tumor site more effectively with a relative longer retention time taking advantage of the nanomaterial-induced endothelial leakiness phenomenon. All these results demonstrate the designed PPI NPs possess enhanced NIR responsive property are to hold a great promise for tumor NIR theranostic applications.
关键词： polypyrrole nanoparticles,photoacoustic imaging,photothermal therapy,Functionalized nanomaterials,near-infrared (NIR) responsive,theranostic treatment
更新于2025-09-23 15:21:21
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Biocompatible superparamagnetic core-shell nanoparticles for potential use in hyperthermia-enabled drug release and as an enhanced contrast agent
摘要： Superparamagnetic iron oxide nanoparticles (SPIONs) and core-shell type nanoparticles, consisting of SPIONs coated with mesoporous silica and/or lipid, were synthesized and tested for their potential theranostic applications in drug delivery, magnetic hyperthermia and as a contrast agent. Transmission Electron Microscopy (TEM) confirmed the size of bare and coated SPIONs was in the range of 5-20 nm and 100-200 nm respectively. The superparamagnetic nature of all the prepared nanomaterials as indicated by Vibrating Sample Magnetometry (VSM) and their heating properties under an AC field confirm their potential for hyperthermia applications. Scanning Column Magnetometry (SCM) data showed that extrusion of bare-SPION (b-SPION) dispersions through a 100 nm polycarbonate membrane significantly improved the dispersion stability of the sample. No sedimentation was apparent after 18 hours compared to a pre-extrusion estimate of 43% settled at the bottom of the tube over the same time. Lipid coating also enhanced dispersion stability. Transversal relaxation time (T2) measurements for the nanoparticles, using a bench-top relaxometer, displayed a significantly lower value of 46 ms, with a narrow relaxation time distribution, for lipid silica coated SPIONs (Lip-SiSPIONs) as compared to that of 1316 ms for the b-SPIONs. Entrapment efficiency of the anticancer drug, Doxorubicin (DOX) for Lip-SPIONs was observed to be 35% which increased to 58% for Lip-SiSPIONs. Moreover, initial in-vitro cytotoxicity studies against human breast adenocarcinoma, MCF-7 cells showed that % cell viability increased from 57% for bSPIONs to 82% for Lip-SPIONs and to 87% for Lip-SiSPIONs. This suggests that silica and lipid coatings improve the biocompatibility of bSPIONs significantly and enhance the suitability of these particles as drug carriers. Hence, the magnetic nanomaterials prepared in this work have potential theranostic properties as a drug carrier for hyperthermia cancer therapy and also offer enhancement of contrast agent efficacy and a route to a significant increase in dispersion stability.
关键词： magnetoliposomes,drug carrier,cancer therapy,colloidal stability,hyperthermia,theranostic,Superparamagnetic iron oxide nanoparticles
更新于2025-09-23 15:21:01
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Carbon Dots as Theranostic Agents || Carbon Dots for Cell Imaging and Diagnostics
摘要： Not only CDs, but many carbon allotropes showing graphitic structure, i.e., honeycomb-like arrangement of carbon atoms, have shown potential for various applications in electronic devices in biosensors and bioimaging agents. Some examples of these are 0D fullerene [274], diamond nanocrystals [123] and carbon dots (CDs), as well as 1D CNT [275], 2D graphene QD (GQDs) [276] and graphene [277]. However, it must be mentioned here that although CDs and GQDs have similar quantum-confined fluorescent carbon materials, CDs have been more used as biosensors and bioimaging agents [278]. Both CD and GQD are mainly composed of sp2 carbon, oxygen and nitrogen elements and other doped heteroatoms [24, 101]; the different spatial arrangements of carbon atoms exhibit distinctive physical and chemical properties [279]. Unlike GQD, the CDs do not have perfect crystal structures [42]. Moreover, CDs exhibit luminance at size < 10 nm, whereas GQDs have size up to 100 nm [280, 281] and are luminescent. Generally, CDs display strong optical absorption in the UV region, with a tail extending out into the visible range (Figure 5.1a), i.e., 280–360 nm. The absorption band could be regulated via surface passivation or modification. CDs show the excitation-dependent emission properties in wavelength and intensity (Figure 5.1b). Other properties that make CD more applicable for biomedical applications are their low cost, high quantum yield, abundant source, low cytotoxicity, and superior chemical and photo stability. Wang et al. [282] have evaluated the cytotoxicity of the CDs prepared by different combinations of precursor of CDs and molecules used for surface functionalization. It is found that in terms of their nanoscale structure and configuration CDs are not intrinsically cytotoxic. The cytotoxicity of CD depends on the selection of surface passivation molecules.
关键词： quantum yield,theranostic agents,bioimaging,carbon dots,photoluminescence,biosensors,cytotoxicity
更新于2025-09-23 15:21:01
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Ag2S-Glutathione Quantum Dots for NIR Image Guided Photothermal Therapy
摘要： Aqueous synthesis of glutathione (GSH) coated Ag2S quantum dots (QD) with strong emission in the medical imaging window (700-900 nm) were prepared from AgNO3. Variations in temperature, time, pH and sulfur source (Na2S and thioacetamide) were studied to tune the emission wavelength and intensity of QDs. The optimum synthesis condition to produce the smallest QDs (ca 7 nm) with the highest quantum yield (70 %) and excellent stability was determined as 50 ℃ and pH 10 where Na2S was used in 2 h reactions. Cytotoxicity was evaluated with MTT assay on HT29 and MCF7 cancer cell lines and indicated no significant toxicity of QDs up to 200 μg/mL. Photothermal Therapy (PTT) potential was first investigated by 795 nm, continuous-wave fiber coupled diode laser using aqueous solutions of QDs and then on HT29 and MCF7 cells. QD (150 μg/mL) treated MCF7 cells almost quantitatively died after 10 min irradiation at 795 nm (700 mW, 1.82 W/cm2) and the viability of HT29 cells dropped to 40%. Most cell death was late apoptotic/necrotic. This study indicates that such laser irradiation procedure and the QDs are safe yet, their combination provides a dramatic cell death upon short laser treatment. PTT coupled with strong intracellular optical signal promotes Ag2S-GSH QDs as potential theranostic nanoparticles.
关键词： glutathione coating,NIR imaging,Ag2S quantum dots,theranostic nanoparticles,photothermal therapy
更新于2025-09-23 15:19:57
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Rhomboidal Pt(II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy
摘要： Fluorescent theranostics probes at the second near-IR region (NIR-II; 1.0–1.7 μm) are in high demand for precise theranostics that minimize autofluorescence, reduce photon scattering, and improve the penetration depth. Herein, we designed and synthesized an NIR-II theranostic nanoprobe 1 that incorporates a Pt(II) metallacycle 2 and an organic molecular dye 3 into DSPE-mPEG5000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]). This design endows 1 with good photostability and passive targeting ability. Our studies show that 1 accurately diagnoses cancer with high resolution and selectively delivers the Pt(II) metallacycle to tumor regions via an enhanced permeability and retention effect. In vivo studies reveal that 1 efficiently inhibits the growth of tumor with minimal side effects. At the same time, improved fluorescent imaging quality and signal-to-noise ratios are shown due to the long emission wavelengths. These studies demonstrate that 1 is a potential theranostic platform for tumor diagnosis and treatment in the NIR-II region.
关键词： metallacycle,image-guided therapy,supramolecular coordination complexes,second near-infrared region,theranostic
更新于2025-09-19 17:15:36
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Targeted and synergic glioblastoma treatment: multifunctional nanoparticles delivering verteporfin as adjuvant therapy for temozolomide chemotherapy
摘要： Despite advances in cancer therapies, glioblastoma multiforme treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low Temozolomide (TMZ) chemotherapeutic selectivity. To improve therapeutic outcomes, in this work we propose two strategies: (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles (m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in Pluronic P85/F127 copolymers. These smart m-NPs can surmount the BBB and co-encapsulate multiple cargoes under optimized conditions. Overall, the present study conducts a rational m-NP design, characterization, and optimizes the formulation conditions. Confocal microscopy studies on T98-G, U87-MG, and U343 glioblastoma cells and on NIH-3T3 normal fibroblast cells show that the m-NPs and the encapsulated drugs are selectively taken up by tumor cells presenting a broad intracellular distribution. The formulations display no toxicity in the absence of light and are not toxic to healthy cells, but they exert a robust synergic action in cancer cells in the case of concomitant PDT/TMZ treatment, especially at low TMZ concentrations and higher light doses, as demonstrated by nonlinear dose–effect curves based on Chou-Talalay method. The results evidenced different mechanisms of action related to the disjoint cell cycle phases at the optimal PDT/TMZ ratio. This effect favors synergism between the PDT and the chemotherapy with TMZ, enhances the antiproliferative effect, and overcomes cross-resistance mechanisms. These results point out that m-NP-based PDT adjuvant therapy is a promising strategy to improve TMZ-based glioblastoma multiforme treatments.
关键词： Verteporfin,Temozolomide,Photodynamic therapy,Nanotechnology,Theranostic
更新于2025-09-19 17:15:36
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Real-time molecular optical micro-imaging of EGFR mutations using a fluorescent erlotinib based tracer
摘要： Background: EGFR mutations are routinely explored in lung adenocarcinoma by sequencing tumoral DNA. The aim of this study was to evaluate a fluorescent-labelled erlotinib based theranostic agent for the molecular imaging of mutated EGFR tumours in vitro and ex vivo using a mice xenograft model and fibred confocal fluorescence microscopy (FCFM). Methods: The fluorescent tracer was synthesized in our laboratory by addition of fluorescein to an erlotinib molecule. Three human adenocarcinoma cell lines with mutated EGFR (HCC827, H1975 and H1650) and one with wild-type EGFR (A549) were xenografted on 35 Nude mice. MTT viability assay was performed after exposure to our tracer. In vitro imaging was performed at 1 μM tracer solution, and ex vivo imaging was performed on fresh tumours excised from mice and exposed to a 1 μM tracer solution in PBS for 1 h. Real-time molecular imaging was performed using FCFM and median fluorescence intensity (MFI) was recorded for each experiment. Results: MTT viability assay confirmed that addition of fluorescein to erlotinib did not suppress the cytotoxic of erlotinib on tumoral cells. In vitro FCFM imaging showed that our tracer was able to distinguish cell lines with mutated EGFR from those lines with wild-type EGFR (p < 0.001). Ex vivo FCFM imaging of xenografts with mutated EGFR had a significantly higher MFI than wild-type (p < 0.001). At a cut-off value of 354 Arbitrary Units, MFI of our tracer had a sensitivity of 100% and a specificity of 96.3% for identifying mutated EGFR tumours. Conclusion: Real time molecular imaging using fluorescent erlotinib is able to identify ex vivo tumours with EGFR mutations.
关键词： Lung cancer,Erlotinib,Theranostic,EGFR,Epidermal growth factor,Fibred confocal fluorescence microscopy,Molecular imaging
更新于2025-09-19 17:15:36