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Graphene quantum dot based charge-reversal nanomaterial for nucleus-targeted drug delivery and efficiency controllable photodynamic therapy
摘要： Graphene quantum dots (GQD), the new zero-dimensional carbon nanomaterial, has been demonstrated as a promising material for biomedical applications due to its good biocompatibility and low toxicity. However, the integration of multiple therapeutic approaches into a nano-sized platform based on the GQD has not been explored yet to our best knowledge. In this report, we regulate the generation of reactive oxygen species (ROS) when using the GQD as a photosensitizer by varying the doping amount of nitrogen atoms to achieve efficiency controllable photodynamic therapy (PDT). On the other hand, charge-reversal (3-Aminopropyl) triethoxysilane (APTES) was employed to conjugate on the surface of GQD for nucleus targeting drug delivery for the first time. The treatment outcome of produced ROS and nucleus-targeting drug delivery was investigated by fluorescence imaging. The results demonstrated that the N-GQD-DOX-APTES in dual roles as a drug carrier and photosensitizer could achieve nucleus-targeting delivery and strong ROS production simultaneously. This approach provides a promising strategy for the development of multifunctional therapy in one nano platform for biomedical applications.
关键词： nucleus-targeted drug delivery,Graphene quantum dots,nitrogen doped graphene quantum dots,charge-reversal,photodynamic therapy
更新于2025-11-21 11:24:58
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Differential photothermal and photodynamic performance behaviors of gold nanorods, nanoshells and nanocages under identical energy conditions
摘要： Various gold (Au) nanostructures have shown promising near infrared (NIR) light-activated phototherapeutic effects; however, their reported photothermal or photodynamic performance behavior is usually inconsistent or even conflicted, dramatically limiting the improvement of phototherapeutic Au nanostructures. The potential reason for this uncertainty is mainly because the photoactivities of Au nanostructures are not evaluated under identical energy conditions. Herein, three Au nanostructures, Au nanorods (NRs), nanoshells (NSs), and nanocages (NCs), were prepared to provide the same localized surface plasmon resonance (LSPR) peaks at 808 nm. All these Au nanostructures (at the same optical density) could fully exert their photoactivities under the identical and optimal energy condition of 808 nm laser irradiation. It was found that these Au nanostructures could induce similar levels of temperature elevation but different levels of reactive oxygen species (ROS) production, where Au NCs exhibited the highest ROS production, followed by Au NSs and NRs. In vitro and in vivo phototherapeutic assessments further supported that Au NCs could cause the most severe cell death and tumor growth regression. This means that the identical incident energy has different contribution to photothermal and photodynamic performance of Au nanostructures, and the corner angle structures of Au NCs compared with NSs and NCs could more efficiently convert the photon energy into photodynamic property. Taken all together, Au NCs hold great potential for phototherapy due to their efficient energy utilization capability.
关键词： reactive oxygen species,photodynamic therapy,gold nanostructures,photothermal therapy,cancer treatment
更新于2025-11-21 11:08:12
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A Near Infrared-Modulated Thermosensitive Hydrogel for Stabilization of Indocyanine Green and Combinatorial Anticancer Phototherapy
摘要： Indocyanine green (ICG), a multifunctional near-infrared (NIR) imaging agent approved by the FDA, has been extensively used in clinical cancer theranosis, but limited by its inherent instability, short plasma half-life and lack of targeting ability. Herein, an in situ formed photothermal network based thermosensitive hydrogel (PNT-gel) constructed by supramolecular cross-linking conjugated polymers was developed for stabilization of ICG and efficient combinatorial photothermal/photodynamic antitumor therapy. While the conjugated polymeric backbone in PNT-gel anchored the aromatic phototherapeutic agent ICG via π–π stacking interactions to avoid premature leakage, it also directly converted low-dose NIR light to induce localized hyperthermia to enhance the photothermal effect. The PNT-gel shows a reversible gel-to-sol upper critical solution temperature (UCST) that is slightly above the body temperature. Therefore, the controlled release of ICG was switched on or off by NIR via photothermal-induced gel-sol transition. In vitro and in vivo antitumor experiments demonstrated that ICG loaded PNT-gel not only efficiently induced the killing of 4T1 cancer cells, but also achieved almost complete eradication of 4T1 cells by one-dose in combinatorial photothermal/photodynamic therapy under irradiation of a low-dose 808 nm laser (0.14 W cm-2). Additionally, the combinational therapy proved to enhance the effectiveness of photodestruction without tumor recurrence compared with intratumoral injection photothermal therapy (PTT) or photodynamic therapy (PDT) treatment alone.
关键词： Near Infrared-Modulated Thermosensitive Hydrogel,Combinatorial Anticancer Phototherapy,Indocyanine Green,Photodynamic Therapy,Photothermal Therapy
更新于2025-11-21 11:08:12
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Biomimetic Metal-Organic Framework Nanoparticles for Cooperatively Combination of Antiangiogenesis and Photodynamic Therapy for Enhanced Efficacy
摘要： Photodynamic therapy (PDT) is a promising anticancer treatment and is clinically approved for different types of tumors. However, current PDT suffers several obstacles, including its neutralization by excess glutathione (GSH) in the tumor tissue and its strongly proangiogenic tumor response. In this work, a biomimic, multifunctional nanoparticle-based PDT agent, combining a tumor-targeted photosensitizer with GSH scavenging and antiangiogenesis therapy, is developed. A porphyrinic Zr–metal–organic framework nanoparticle is used simultaneously as the photosensitizer and the delivery vehicle of vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib. The core nanoparticles are wrapped in MnO2 to consume the intratumoral GSH and then decorated with a tumor cell membrane camouflage. After intravenous administration, the nanoparticles selectively accumulate in tumor through homotypic targeting mediated by the biomimic decoration, and the combination of enhanced PDT and antiangiogenic drug significantly improves their tumor inhibition efficiency. This study provides an integrated solution for mechanism-based enhancement of PDT and demonstrates the encouraging potential for multifunctional nanosystem applicable for tumor therapy.
关键词： glutathione metabolism,photodynamic therapy,MOF,angiogenesis inhibition,biomimetic nanoparticle
更新于2025-11-21 11:08:12
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Screening of two-photon activated photodynamic therapy sensitizers using a 3D osteosarcoma model
摘要： Photodynamic therapy (PDT) involves a photosensitizing agent activated with light to induce cell death. Two-photon excited PDT (TPE-PDT) offers numerous benefits compared to traditional one-photon induced PDT, including an increased penetration depth and precision. However, the in vitro profiling and comparison of two-photon photosensitizers (PS) are still troublesome. Herein, we report the development of an in vitro screening platform of TPE-PS using a 3D osteosarcoma cell culture. The platform was tested using three different two-photon (2P) active compounds – a 2P sensitizer P2CK, a fluorescent dye Eosin Y, and a porphyrin derivative (TPP). Their 2P absorption cross-sections (σ2PA) were characterised using a fully automated z-scan setup. TPP exhibited a remarkably high σ2PA at 720 nm (8865 GM) and P2CK presented a high absorption at 850 nm (405 GM), while Eosin Y had the lowest 2P absorption at the studied wavelengths (<100 GM). The cellular uptake of PS visualized using confocal laser scanning microscopy showed that both TPP and P2CK were internalized by the cells, while Eosin Y stayed mainly in the surrounding media. The efficiency of the former two TPE-PS was quantified using the PrestoBlue metabolic assay, showing a significant reduction in cell viability after two-photon irradiation. The possibility of damage localization was demonstrated using a co-culture of adipose derived stem cells together with osteosarcoma spheroids showing no signs of damage to the surrounding healthy cells after TPE-PDT.
关键词： two-photon excited photodynamic therapy,PrestoBlue assay,photosensitizers,cellular uptake,localized damage,z-scan,3D osteosarcoma model
更新于2025-11-21 11:08:12
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Two-photon excited organic nanoparticles for chemo-photodynamic therapy
摘要： Drug molecules assembling nanomedicines possess several advantages, including precise molecular structure, various combinations of theraputic agents and high content of drugs. In this work, paclitaxel dimer and two-photo photosensitizer were devised and synthesized, which could coassemble into nanoparticles (Co-NPs) in aqueous medium through nanopreicipitation method. As-synthesized Co-NPs possess the uniform size of about 80 nm and great stability in physiological condition, and could produce the singlet oxygen upon near-infrared light irradiation. The Co-NPs indicate enhanced cellular uptake and endosomal escape upon irradiation, which result in the synergistic enhancement of cytotoxicity towards cancer cells and growth inhibition of human cervical cancer tumors. We believed this combination therapy based on organic nanoparticles represent a new and important development in the cancer therapy.
关键词： two-photon,photodynamic therapy,paclitaxel,chemotherapy
更新于2025-11-21 11:08:12
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Core-shell metal-organic frameworks with fluorescence switch to trigger an enhanced photodynamic therapy
摘要： The design of hybrid metal-organic framework (MOF) nanomaterials by integrating inorganic nanoparticle into MOF (NP@MOF) has demonstrated outstanding potential for obtaining enhanced, collective, and extended novel physiochemical properties. However, the reverse structure of MOF-integrated inorganic nanoparticle (MOF@NP) with multifunction has rarely been reported. Methods: We developed a facile in-situ growth method to integrate MOF nanoparticle into inorganic nanomaterial and designed a fluorescence switch to trigger enhanced photodynamic therapy. The influence of “switch” on the photodynamic activity was studied in vitro. The in vivo mice with tumor model was applied to evaluate the “switch”-triggered enhanced photodynamic therapy efficacy. Results: A core-satellites structure with fluorescence off and on function was obtained when growing MnO2 on the surface of fluorescent zeolitic imidazolate framework (ZIF-8) nanoparticles. Furthermore, A core-shell structure with photodynamic activity off and on function was achieved by growing MnO2 on the surface of porphyrinic ZrMOF nanoparticles (ZrMOF@MnO2). Both the fluorescence and photodynamic activities can be turned off by MnO2 and turned on by GSH. The GSH-responsive activation of photodynamic activity of ZrMOF@MnO2 significantly depleted the intracellular GSH via a MnO2 reduction reaction, thus triggering an enhanced photodynamic therapy efficacy. Finally, the GSH-reduced Mn2+ provided a platform for magnetic resonance imaging-guided tumor therapy. Conclusion: This work highlights the impact of inorganic nanomaterial on the MOF properties and provides insight to the rational design of multifunctional MOF-inorganic nanomaterial complexes.
关键词： Core-shell structure,Metal-organic frameworks,Fluorescence switch,Photodynamic therapy
更新于2025-11-21 11:08:12
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Perfluorocarbon-Loaded and Redox-Activatable Photosensitizing Agent with Oxygen Supply for Enhancement of Fluorescence/Photoacoustic Imaging Guided Tumor Photodynamic Therapy
摘要： The wide clinical application of photodynamic therapy (PDT) is hampered by poor water solubility, low tumor selectivity, and nonspecific activation of photosensitizers, as well as tumor hypoxia which is common for most solid tumors. To overcome these limitations, tumor-targeting, redox-activatable, and oxygen self-enriched theranostic nanoparticles are developed by synthesizing chlorin e6 (Ce6) conjugated hyaluronic acid (HA) with reducible disulfide bonds (HSC) and encapsulating perfluorohexane (PFH) within the nanoparticles (PFH@HSC). The fluorescence and phototoxicity of PFH@HSC nanoparticles are greatly inhibited by a self-quenching effect in an aqueous environment. However, after accumulating in tumors through passive and active tumor-targeting, PFH@HSC appear to be activated from “OFF” to “ON” in photoactivity by the redox-responsive destruction of the vehicle’s structure. In addition, PFH@HSC can load oxygen within lungs during blood circulation, and the oxygen dissolved in PFH is slowly released and diffuses over the entire tumor, finally resulting in remarkable tumor hypoxia relief and enhancement of PDT efficacy by generating more singlet oxygen. Taking advantage of the excellent imaging performance of Ce6, the tumor accumulation of PFH@HSC can be monitored by fluorescent and photoacoustic imaging after intravenous administration into tumor-bearing mice. This PFH@HSC nanoparticle might have good potential for dual imaging-guided PDT in hypoxic solid tumor treatment.
关键词： tumor hypoxia,hyaluronic acid nanoparticles,perfluorocarbon,redox-responsive,photodynamic therapy
更新于2025-11-19 16:46:39
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Photosensitizer–conjugated Cu-In-S heterostructured nanorods for cancer targeted photothermal/photodynamic synergistic therapy
摘要： Photo-activated therapy is a non-invasive and promising medical technology for the treatment of cancers. Herein, we present Ce6-HA-CIS phototherapeutic nanohybrids composed of Cu-In-S (CIS) heterostructured nanorod (HS-rod), chlorin e6 (Ce6), and hyaluronic acid (HA) for the use in targeted photodynamic/photothermal therapy (PDT/PTT). In the Ce6-HA-CIS nanohybrids, the CIS HS-rod was investigated as a PTT agent to convert light into thermal energy, with Ce6 acting as a PDT agent to generate singlet oxygen (1O2). HA encapsulated the surface of the CIS HS-rod and aided the hydrophobic CIS HS-rod in achieving aqueous solubility. HA also acts as a tumor-specific targeting vector of cancer cells bearing the cluster determinant 44 receptor. Under light irradiation, the fabricated Ce6-HA-CIS nanohybrids exhibited high photothermal conversion efficiency, good photo-stability, and satisfactory photodynamic activity. In vitro and in vivo experiments demonstrated that Ce6-HA-CIS showed low cytotoxicity and synergistic photodynamic and photothermal cancer cell killing effects as compared to PTT or PDT agents alone. Therefore, these phototherapeutic nanohybrids may enhance cancer therapy in future clinical applications.
关键词： Cu-In-S,Nanohybrids,Hyaluronic acid,Photodynamic therapy,Photothermal therapy
更新于2025-11-14 17:04:02
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Albumin-functionalized CuFeS2/photosensitizer nanohybrid for single-laser-induced folate receptor-targeted photothermal and photodynamic therapy
摘要： Multimodal therapy is an emerging medical intervention to overcome the current limitation in cancer therapy combining treatment modalities with different mechanisms of action to eradicate tumors. This study demonstrates a targeted multifunctional bovine serum albumin (BSA)-functionalized CuFeS2/chlorin e6 (Ce6) for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) effects. The CuFeS2 nanocrystals were synthesized through a simple heating-up approach and transferred into an aqueous phase using BSA in an ultrasonic-assisted microemulsion method. The as-prepared CuFeS2@BSA nanoparticles further conjugated with folic acid (FA) followed by attachment of Ce6 to form the Ce6:CuFeS2@BSA-FA nanohybrid with improved solubility and strong near-infrared (NIR) absorbance and fluorescence. It is the first report to fabricate the targeted Ce6:CuFeS2@BSA-FA hybrid and evaluates their synergistic PTT/PDT effect using a single laser. The Ce6:CuFeS2@BSA-FA hybrid showed lower toxicity in vitro (HeLa and HepG2 cells) and in vivo (zebrafish embryos), while they are selectively recognized and internalized by HeLa cells that over-express folate receptors. Compared to each modality applied separately, the combined single-laser-induced PTT and PDT treatment showed the enhanced generation of heat and reactive oxygen species (ROS) with synergistic cancer killing under 671 nm laser irradiation (10 min, 1 W/cm2). As a biocompatible targeted nanoprobe, the multifunctional nanohybrid holds promise in combined PDT/PTT synergistic therapy to achieve better efficacy.
关键词： Photodynamic therapy,Single laser,Photosensitizers,Photothermal therapy,CuFeS2
更新于2025-11-14 17:04:02