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Development of Photo-Activated ROS-Responsive Nanoplatform as a Dual-Functional Drug Carrier in Combinational Chemo-Photodynamic Therapy
摘要： Dual functional drug carrier has been a modern strategy in cancer therapy because it is a platform to elicit additive and synergistic effects through combination therapy. Photo-activated external stimuli such as reactive oxygen species (ROS) also ensure adequate drug delivery in a precise temporal and spatial manner. However, current ROS-responsive drug delivery systems usually require tedious synthetic procedures. A facile one-pot approach has been reported herein, to obtain self-assembled polymeric nanocarriers (NCs) for simultaneous paclitaxel (PTX)- and Rose Bengal (RB)-loading to achieve combined chemo-photodynamic therapy and controlled drug release in responsive to a light-induced ROS stimulus. To encapsulate these hydrophobic and hydrophilic drugs, chitosan (CTS), branched polyethylenimine (bPEI) and polyvinyl alcohol (PVA) were selected and fabricated into nanoblended matrices through an oil-in-water emulsion method. The amphiphilic properties of CTS permit simultaneous entrapment of PTX and RB, while the encapsulation efficiency of RB was further improved by increasing the amount of short-chain bPEI. During the one-step assembly process, bovine serum albumin (BSA) was also added to condense the cationic tripolymer mixtures into more stable nanocarriers (BNCs). Hyaluronic acid (HA) was subsequently grafted onto the surface of BNCs through electrostatic interaction, leading to the formation of HA-BSA/CTS/PVA/bPEI-blended nanocarriers (HBNCs) to achieve an efficient prostate-cancer-cell uptake. Importantly, in response to external light irradiation, HBNCs become destabilized owing to the RB-mediated photodynamic action. It allows an on-demand dual-payload release to evoke a simultaneous photodynamic and chemo treatment for cancer cell eradication. Thus, HBNCs present a new promising approach that exhibits a specific vulnerability to RB-induced photosensitization. The consequent dual-cargo release is also expected to successfully combat cancer through a synergistic anti-tumor effect.
关键词： ROS-responsive,photodynamic therapy,nanocarrier,chemotherapy,combined therapy
更新于2025-09-23 15:23:52
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Intratumorally Injected Photothermal Agent-Loaded Photodynamic Nanocarriers for Ablation of Orthotopic Melanoma and Breast Cancer
摘要： Traditional chemotherapy of cancers may lead to serious adverse reactions due to little drug distribution in tumors. Here, a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) was used for local treatment of orthotopic melanoma and breast cancer via intratumoral (i.t.) injection of photothermal agent-loaded photodynamic nanocarriers. A hydrophobic derivative of indocyanine green, DCC, was synthesized and entrapped into a pH-sensitive photosensitizer-core copolymer, PDCZP, to form DCC@PDCZP. The nanocarriers showed remarkable fluorescence, high singlet oxygen quantum yields, and strong photothermal effect. Flow cytometry suggested that the nanocarriers were efficiently internalized by cancer cells. Near infrared thermal imaging and fluorescence self-imaging showed that the i.t. injected DCC@PDCZP mainly remained in the tumors but the intravenous (i.v.) nanocarriers were distributed a little. One i.t. injection of DCC@PDCZP was enough to ablate the orthotopic B16-F10 and 4T1 mouse tumors under 830 nm and 660 nm irradiation at 4 hours post-injection. More importantly, no local recurrences were found though scabs were formed at 9 days post-treatment. The major anticancer mechanisms included improvement of cancer cell necrosis due to hyperthermia, inhibition of neovascularization, and enhancement of cell apoptosis. The i.t. injection of PTT/PDT nanoformulations is thus a promising local treatment of superficial tumors.
关键词： zinc phthalocyanine,intratumoral injection,melanoma,indocyanine green,breast cancer,photodynamic therapy,photothermal therapy
更新于2025-09-23 15:23:52
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Dual-responsive molybdenum disulfide/copper sulfide-based delivery systems for enhanced chemo-photothermal therapy
摘要： Molybdenum disul?de (MoS2)-based drug delivery systems have shown considerable potential in cancer nanomedicines. In this work, a multifunctional nanoplatform comprising MoS2 nanosheets decorated with copper sul?de (CuS) and further functionalized with polyethylene glycol (PEG) is reported. The resultant material has a particle size of approximately 115 nm, and can be loaded with doxorubicin (DOX) to a loading capacity of 162.3 mg DOX per g of carrier. Drug release is triggered by two stimuli (near infrared (NIR) irradiation and pH), and the carrier is shown to have excellent colloidal stability. The presence of both MoS2 and CuS leads to very high photothermal conversion ef?ciency (higher than with MoS2 alone). In vitro experiments revealed that the blank CuS-MoS2-SH-PEG carrier is biocompatible, but that the synergistic application of chemo-photothermal therapy (in the form of CuS-MoS2-SH-PEG loaded with DOX and NIR irradiation) led to greater cell death than either chemotherapy (CuS-MoS2-SH-PEG(DOX) but no NIR) or photothermal therapy (CuS-MoS2-SH-PEG with NIR). A cellular uptake study demonstrated that the nanoplatform can ef?ciently enter tumor cells, and that uptake is enhanced when NIR is applied. Overall, the functionalized MoS2 material developed in this work exhibits great potential as an ef?cient system for dual responsive drug delivery and synergistic chemo-photothermal therapy. The route employed in our work thus provides a strategy to enhance photothermal ef?cacy for transition metal dichalcogenide drug delivery systems.
关键词： Chemotherapy,Drug delivery,MoS2,Photothermal therapy,Synergistic therapy
更新于2025-09-23 15:23:52
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2D Ti2C (MXene) as a novel highly efficient and selective agent for photothermal therapy
摘要： Photothermal therapy (PTT) has shown significant potential for anti-cancer modality. In this report, according to our best knowledge, we explore for the first time Ti2C-based MXene as a novel, highly efficient and selective agent for photothermal therapy (PTT). Ti2C superficially modified with PEG was obtained from the layered, commercially available Ti2AlC MAX phase in the process of etching aluminum layers using concentrated HF, and characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HREM) as well as X-Ray photoelectron spectroscopy for chemical analysis (ESCA-XPS). The PEG-coated Ti2C flakes showed a satisfactory photothermal conversion efficacy (PTCE) and good biocompatibility in wide range of the tested concentrations. Through in vitro studies, the PEG-modified Ti2C demonstrated notable NIR-induced ability to cancerous cells’ ablation with minimal impact on non-malignant cells up to the concentration of 37.5 μg ml-1. The applied doses of Ti2C_PEG in our work were even 24 times lower comparing other MXene-based photothermal agents. This work is expected to expand the utility of 2D MXenes to biomedical applications through the development of an entirely novel agents for photothermal therapy.
关键词： photothermal therapy,biological activity,light-to-heat conversion,2D Ti2C MXenes,anticancer therapy
更新于2025-09-23 15:23:52
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Rod in Tube: A Novel Nanoplatform for Highly Effective Chemo-photothermal Combination Therapy Towards Breast Cancer
摘要： Gold nanorods (GNRs) and doxorubicin (DOX) were loaded into the lumen of halloysite nanotubes (HNTs) via a rapid synthesis process (2 min) and physical adsorption. The targeting molecules of folic acid (FA) are then conjugated to HNTs via reactions with bovine serum albumin (BSA). The formation of GNRs in HNTs was verified by different techniques. The Au-HNTs-DOX@BSA-FA shows maximum of 26.8 oC temperature rising after 8 min 808-nm laser irradiation under 0.8 W cm-2. The functionalized HNTs exhibited stronger chemotherapeutic effect under laser irradiation, since the laser could promote the release of DOX and temperature rising. Au-HNTs-DOX@BSA-FA treated MCF-7 cells exhibited survival rate of 7.4% after laser irradiation. Au-HNTs-DOX@BSA-FA treatment do not induce an obvious toxicity in blood biochemistry, liver and kidney function in normal mice. In vivo chemo-photothermal treatment towards 4T1-bearing mice suggested Au-HNTs-DOX@BSA-FA exhibited remarkable tumor-targeted efficiency and good controlled-release effect for DOX. Also, the nanoparticles exhibited a rapid photothermal performance and inhibiting ability of the growth of tumor. Due to the synergistic effect of chemical-photothermal therapy, the toxicity of DOX to normal tissues was reduced on the premise of ensuring the same curative effect with a low dosage of 0.32 mg kg-1. This novel chemo-photothermal therapy nanoplatform provided a safe, rapid, effective, and cheap choice for treatment of breast tumor both in vitro and in vivo.
关键词： doxorubicin,photothermal therapy,halloysite nanotubes,chemo-photothermal therapy,gold nanorods
更新于2025-09-23 15:23:52
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Contemporary Polymer-Based Nanoparticle Systems for Photothermal Therapy
摘要： Current approaches for the treatment of cancer, such as chemotherapy, radiotherapy, immunotherapy, and surgery, are limited by various factors, such as inadvertent necrosis of healthy cells, immunological destruction, or secondary cancer development. Hyperthermic therapy is a promising strategy intended to mitigate many of the shortcomings associated with traditional therapeutic approaches. However, to utilize this approach effectively, it must be targeted to specific tumor sites to prevent adverse side effects. In this regard, photothermal therapy, using intravenously-administered nanoparticle materials capable of eliciting hyperthermic effects in combination with the precise application of light in the near-infrared spectrum, has shown promise. Many different materials have been proposed, including various inorganic materials such as Au, Ag, and Germanium, and C-based materials. Unfortunately, these materials are limited by concerns about accumulation and potential cytotoxicity. Polymer-based nanoparticle systems have been investigated to overcome limitations associated with traditional inorganic nanoparticle systems. Some of the materials that have been investigated for this purpose include polypyrrole, poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), polydopamine, and polyaniline. The purpose of this review is to summarize these contemporary polymer-based nanoparticle technologies to acquire an understanding of their current applications and explore the potential for future improvements.
关键词： polydopamine,polypyrrole,polymeric nanoparticle,photothermal therapy,polyaniline
更新于2025-09-23 15:23:52
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Targeted delivery of reduced graphene oxide nanosheets using multifunctional ultrasound nanobubbles for visualization and enhanced photothermal therapy
摘要： Ultrasound molecular imaging as a promising strategy, which involved the use of molecularly targeted contrast agents, combined the advantages of contrast-enhanced ultrasound with the photothermal effect of reduced graphene oxide (rGO). Methods and results: The heparin sulfate proteoglycan glypican-3 (GPC3) is a potential molecular target for hepatocellular carcinoma (HCC). In this study, we covalently linked biotinylated GPC3 antibody to PEGylated nano-rGO to obtain GPC3-modified rGO-PEG (rGO-GPC3), and then combined rGO-GPC3 with avidinylated nanobubbles (NBs) using biotin-avidin system to prepare NBs-GPC3-rGO with photothermal effect and dispersibility, solubility in physiological environment. The average size of NBs-GPC3-rGO complex was 700.4±52.9 nm due to the polymerization of biotin-avidin system. Scanning electron microscope (SEM) showed NBs-GPC3-rGO attached to human hepatocellular carcinoma HepG2 cell. The ultrasound-targeted nanobubble destruction (UTND) technology make use of the physical energy of ultrasound exposure for the improvement of rGO delivery. Compared with other control groups, the highest nanobubble destruction efficiency of NBs-GPC3-rGO was attributed to the dissection effect of rGO on UTND. This is a positive feedback effect that leads to an increase in the concentration of rGO around the HepG2 cell. So NBs-GPC3-rGO using UTND and near-infrared (NIR) irradiation resulted in cell viability within 24 h, 48 h, 72 h lower than other treatment groups. Conclusion: This work established NBs-GPC3-rGO as an ultrasonic photothermal agent due to its suitable size, imaging capability, photothermal efficiency for visual photothermal therapy in vitro.
关键词： ultrasound-targeted nanobubble destruction,photothermal therapy,glypican-3,reduced graphene oxide,HepG2 cell
更新于2025-09-23 15:23:52
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NIR light-triggered gelling <i>in situ</i> of porous silicon nanoparticles/PEGDA hybrid hydrogels for localized combinatorial therapy of cancer cells
摘要： Porous silicon-based nanocomposite hydrogels were readily constructed with the gelation of poly(ethylene glycol) double acrylates (PEGDA) macromers, due to the initiation of singlet oxygen photosensitized with porous silicon nanoparticles (PSiNPs) under near-infrared (NIR) light irradiation. Multifunctional PSiNPs/PEGDA nanocomposite hydrogels showed strong ?uorescence, excellent biodegradability, signi?cant photothermal effect, and sustained drug release with high ef?ciency (>80%). Finally, in situ growth of PSiNPs/PEGDA hybrid hydrogels on cancer cells was also achieved by NIR light, and then their biodegradation, drug release and synergistic chemo-phototherapeutic ef?cacy were further demonstrated, which could provide a signi?cant localized inhibition for the viability, adherence, and migration of cancer cells in vitro. Thus, we suggested that these resultant hybrid hydrogels would have important potential on local cancer therapy in future clinical practice.
关键词： porous silicon nanoparticles,hybrid hydrogels,therapy,insitu gelation,localized cancer
更新于2025-09-23 15:23:52
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PET/CT with Fluorodeoxyglucose During Neoadjuvant
摘要： Objective: The aim of the present study is to evaluate the accuracy of Positron Emission Tomography/Computed Tomography (PET/CT) with Fluorodeoxyglucose ([18F]FDG) to predict treatment response in patients with locally advanced rectal cancer (LARC) during neoadjuvant chemoradiotherapy. Patients and methods: Forty-one LARC patients performed [18F]FDG-PET/CT at baseline (PET0). All patients received continuous capecitabine concomitant to radiotherapy on the pelvis, followed by intermittent capecitabine until two weeks before curative surgery. [18F]FDG-PET/CT was also carried out at 40 Gy-time (PET1) and at the end of neoadjuvant therapy (PET2). PET imaging was analysed semi-quantitatively through the measurement of maximal standardised uptake value (SUVmax) and the tumour volume (TV). Histology was expressed through pTNM and Dworak tumor regression grading. Patients were categorised into responder (downstaging or downsizing) and non-responder (stable or progressive disease by comparison pretreatment parameters with clinical/pathological characteristics posttreatment/after surgery). Logistic regression was used to evaluate SUVmax and TV absolute and percent reduction as predictors of response rate using gender, age, and CEA as covariates. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Survivals were compared by the Log-Rank test. Results: Twenty-three responders (9 ypCR, 14 with downstaged disease) and 18 non-responders showed differences in terms of both early and posttreatment SUVmax percent reduction (median comparison: responder = 63.2%, non-responder = 44.2%, p = 0.04 and responder = 76.9%, non-responder = 61.6%, p = 0.06 respectively). The best predictive cut-offs of treatment response for early and post-treatment SUVmax percent reduction were ≥57% and ≥66% from baseline (p = 0.02 and p = 0.01 respectively). Conclusions: [18F]FDG-PET/CT is a reliable technique for evaluating therapy response during neoadjuvant treatment in LARC, through a categorical classification of the SUV max reduction during treatment.
关键词： neoadjuvant therapy,PET/CT,rectal cancer,fluorodeoxyglucose
更新于2025-09-23 15:23:52
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Oxidative stress generated by irradiation of a zinc(II) phthalocyanine induces a dual apoptotic and necrotic response in melanoma cells
摘要： Melanoma is an aggressive form of skin carcinoma, highly resistant to traditional therapies. Photodynamic therapy (PDT) is a non-invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. In this work we evaluated the effect of a cationic zinc(II) phthalocyanine (Pc13) as photosensitizer on a panel of melanoma cells. Incubation with Pc13 and irradiation induced a concentration and light dose-dependent phototoxicity. In order to study the mechanism underlying Pc13-related cell death and to compare the effect of different doses of PDT, the most sensitive melanoma B16F0 cells were employed. By confocal imaging we showed that Pc13 targeted lysosomes and mitochondria. After irradiation, a marked increase in intracellular reactive oxygen species was observed and a complete protection from Pc13 phototoxicity was reached in the presence of the antioxidant trolox. Acridine orange/ethidium bromide staining showed morphological changes indicative of both apoptosis and necrosis. Biochemical hallmarks of apoptosis, including a significant decrease in the expression levels of Bcl-2, Bcl-xL and Bid and mitochondrial membrane permeabilization, were observed at short times post irradiation. The consequent release of cytochrome c to cytosol and caspase-3 activation led to PARP-1 cleavage and DNA fragmentation. Simultaneously, a dose dependent increase of lactate dehydrogenase in the extracellular compartment of treated cells revealed plasma membrane damage characteristic of necrosis. Taken together, these results indicate that a dual apoptotic and necrotic response is triggered by Pc13 PDT-induced oxidative stress, suggesting that combined mechanisms of cell death could result in a potent alternative for melanoma treatment.
关键词： Necrosis,Mitochondrial membrane permeabilization,Apoptosis,Reactive oxygen species,Photodynamic therapy,Cationic phthalocyanine
更新于2025-09-23 15:23:52