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Hyaluronic acid functionalized nanoparticles loaded with IR780 and DOX for cancer chemo-photothermal therapy
摘要： IR780 is a near infrared (NIR) dye with a huge potential to be applied in cancer phototherapy and imaging. However, IR780 poor water solubility and acute cytotoxicity limit its direct use in cancer theragnostic. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was used, for the first time, in the preparation of polymeric nanoparticles (HPN) encapsulating IR780 aimed to be applied in breast cancer therapy. Furthermore, HPN co-encapsulating IR780 and Doxorubicin (DOX) were also produced in order to further enhance the therapeutic effectiveness of this nanoformulation. The results revealed that HPN were able to successfully encapsulate IR780 (IR-HPN) and the IR780-DOX combination (IR/DOX-HPN). Furthermore, the encapsulation of IR780 in HPN improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential, as well as its cytocompatibility. The 2D in vitro cell uptake studies demonstrated that the nanostructures displayed a higher internalization by breast cancer cells than by normal cells. In addition, the assays performed in 3D in vitro models of breast cancer revealed that HPN can penetrate into spheroids. Furthermore, the 3D in vitro studies also demonstrated that the combined application of IR-HPN and NIR light was unable to induce cytotoxicity on spheroids. In contrast, IR/DOX-HPN produced a decrease on spheroids cells’ viability, and their combination with NIR light induced an even stronger therapeutic effect, thus revealing the potential of these nanoparticles for cancer chemo-phototherapy.
关键词： Cancer,Polymeric Nanoparticles,Chemotherapy,IR780,Photothermal therapy,Doxorubicin
更新于2025-11-21 11:08:12
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A nano-complex system to overcome antagonistic photo-chemo combination cancer therapy
摘要： Photo-Chemo combination therapy has been intensively investigated for treatment of cancers, especially multidrug resistance cancer. However, antagonistic interactions between chemo-drugs and photosensitizers are frequently reported, and drugs doses and treatment sequences have been changed to overcome the problems. We observed the antagonistic effect by a decrease in singlet oxygen generation from the photosensitizer when Dox was in close physical proximity. To control the distance between Dox and the photosensitizer, we developed a novel pH-sensitive poly ionomer complex system composed of PEG-PLL(-g-Ce6) [Chlorin e6 grafted poly(ethylene glycol)-poly(L-lysine)] and PEG-PLL(-g-DMA)-PLA [2,3-dimethylmaleic anhydride grafted poly(ethylene glycol)-poly(L-lysine)-poly(lactic acid)] and evaluated this system with regard to singlet oxygen generation and antiproliferative activity against MCF-7/Dox cells. Enhanced singlet oxygen generation and antiproliferative activities were observed in vitro and in vivo for the poly ionomer complex system compared to PEG-PLL(-g-Ce6)-PLA/Dox due to the change in distance between Dox and Ce6 in the PIC system under acidic conditions. Our results highlight the importance of interactions between co-loaded drugs in combination therapy, and provide new insights into design principles for tailor-made nanomedicine platforms.
关键词： pH sensitive,chlorin e6,photo-chemo combination therapy,MDR,doxorubicin,synergism
更新于2025-11-21 11:01:37
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PEGylated doxorubicin cloaked nano-graphene oxide for dual-responsive photochemical therapy
摘要： Graphene oxide (GO) own huge surface area and high drug loading capacity for aromatic molecules, such as doxorubicin (DOX). However, its biocompatibility is poor and it might agglomerate in physiological condition. Chemical modification of GO with hydrophilic polymer, especially PEGylation, was a common method to improve its biocompatibility. But the chemical modification of GO was complicated, and its drug loading capacity might be reduced because of the occupation of its functional groups. In this study, DOX-PEG polymers with different PEG molecular weight were synthesized to modify nano graphene oxide (NGO) to simultaneously realize the solubilization of NGO and the high loading capacity of DOX. The result showed that the drug release of NGO@DOX-PEG was pH sensitive. NIR irradiation could augment the drug release, cellular uptake, cytotoxicity and nuclear translocation of nanodrugs. Among the three kinds of nanodrugs, NGO@DOX-PEG5K was superior to others. It suggested that after conjugating with PEG, the bond between DOX-PEG and NGO was weakened, which resulted in a better drug release and treatment effect. In summary, the NIR and pH dual-responsive NGO@DOX-PEG nanodrugs were developed by noncovalent modification, and it demonstrated excellent biocompatibility and photochemical therapeutic effect, presenting a promising candidate for antitumor therapy, especially NGO@DOX-PEG5K.
关键词： Nano-drug Delivery System,pH sensitive,Nano-Graphene Oxide,photochemical therapy,Doxorubicin
更新于2025-09-23 15:23:52
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Blood Interactions, Pharmacokinetics and Depth-Dependent Ablation of Rat Mammary Tumors with Photoactivatable, Liposomal Doxorubicin
摘要： Photosensitizers can be integrated with drug delivery vehicles to develop chemophototherapy agents with anti-tumor synergy between chemo- and photo- components. Long-circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes. Hematological effects of endotoxin-minimized LC-Dox-PoP were characterized via standardized assays. In vitro interaction with erythrocytes, platelets, and plasma coagulation cascade were generally unremarkable while complement activation was found to be similar to that of commercial Doxil. Blood partitioning suggested both the Dox and PoP components of LC-Dox-PoP were stably entrapped or incorporated in liposomes. This was further confirmed with pharmacokinetic studies in Fischer rats, which showed the PoP and Dox components of the liposomes both had nearly identical, long circulation half-lives (25-26 hours). In a large orthotopic mammary tumor model in Fischer rats, following intravenous dosing (2 mg/kg Dox), the depth of enhanced Dox delivery in response to 665 nm laser irradiation was over 1 cm. LC-Dox-PoP with laser treatment cured or potently suppressed tumor growth, with greater efficacy observed in tumors 0.8-1.2 cm compared to larger ones. The skin at the treatment site healed within approximately 30 days. Taken together, these data provide insight into nanocharacterization and photo-ablation parameters for a chemophototherapy agent.
关键词： doxorubicin,chemophototherapy,ablation,nanocharacterization,Liposomes
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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The synthesis and application of nano doxorubicin-indocyanine green matrix metalloproteinase-responsive hydrogel in chemophototherapy for head and neck squamous cell carcinoma
摘要： Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies, with high rates of mortality and morbidity worldwide. Owing to the special anatomical location of this tumor, an effective, minimally invasive treatment with low systemic toxicity is highly desirable. Hydrogels have shown great potential for tumor-targeting therapy, with excellent performance. However, there have been few reports on co-loading photosensitizers and chemotherapeutic drugs into hydrogels. In this study, we synthesized a nano doxorubicin-indocyanine green matrix metalloproteinase (MMP)-responsive hydrogel (denoted as NDIMH), combining chemotherapy and phototherapy, to achieve superior antitumor efficacy. Methods: First, NDIMH was synthesized and characterized by scanning electron microscopy and drug-release assays. Second, the photosensitivity properties and antitumor efficiency of this drug delivery system were studied in vivo and in vitro. Last, the imaging and biodistribution of NDIMH were monitored using the Maestro EX in vivo imaging system. Results: The nanodrugs loaded into the smart hydrogel exhibited uniform size distribution, excellent size stability, and a sustained release in the presence of MMP-2. NDIMH showed ideal photosensitivity characteristics under light. NDIMH with 808 nm near-infrared (NIR) irradiation effectively inhibited the viability, invasion, and metastasis of SCC-15 in vitro. After intratumoral injection of NDIMH with 808 nm NIR illumination, the hydrogels exhibited favorable synergistic antitumor efficacy and acceptable biosafety. Additionally, fluorescence imaging showed that NDIMH could significantly improve the retention of nanodrugs at the tumor site. Conclusion: The intratumoral injection of NDIMH with 808 nm NIR irradiation could be a promising chemophototherapy alternative for HNSCC.
关键词： doxorubicin,MMP-responsive,chemophototherapy,hydrogel,indocyanine green
更新于2025-09-23 15:22:29
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PEGylated mesoporous Bi2S3 Nanostars loaded with Chlorin e6 and doxorubicin for fluorescence/CT imaging-guided multimodal therapy of Cancer
摘要： Taking advantage of the mesoporous structure of bismuth sulfide nanostars (Bi2S3 NSs), a chemotherapeutic drug of doxorubicin (DOX) and a photosensitizer of chlorin e6 (Ce6) were concurrently loaded in the PEGylated Bi2S3 NSs to formulate a multifunctional nanocomplex (BPDC NSs) for theranostics. BPDC NSs have excellent photothermal conversion efficiency and a capacity of yielding reactive oxygen species (ROS) upon laser irradiation, and can realize on-demand drug release by either pH-activation or thermal induction. Accumulation of the nanodrug could be monitored in real-time by infrared thermal imaging, fluorescence imaging and computed tomography (CT). More importantly, the combination effects of photothermal therapy (PTT), photodynamic therapy (PDT) and chemotherapy was demonstrated to dramatically suppress solid tumors without recurrence in vivo. Featured by the low systemic toxicity and high biocompatibility, this nanoplatform could be a promising derivative of Bi2S3 NSs for imaging-guided theranostics of cancer.
关键词： Controlled drug release,Cancer theranostics,Doxorubicin,Chlorin e6,Bismuth (Bi) chalcogenides
更新于2025-09-23 15:22:29
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Self-assembly of porphyrin-grafted lipid into nanoparticles encapsulating doxorubicin for synergistic chemo-photodynamic therapy and fluorescence imaging
摘要： The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy. In this experiment, we utilize our previously synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy.
关键词： photodynamic therapy,doxorubicin,theranostics,chemotherapy,porphyrin
更新于2025-09-23 15:21:21
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Thermoplasmonica??Triggered Release of Loads from DNAa??Modified Hydrogel Microcapsules Functionalized with Au Nanoparticles or Au Nanorods
摘要： Microcapsules consisting of hydrogel shells cross-linked by glucosamine–boronate ester complexes and duplex nucleic acids, loaded with dyes or drugs and functionalized with Au nanoparticles (Au NPs) or Au nanorods (Au NRs), are developed. Irradiation of Au NPs or Au NRs results in the thermoplasmonic heating of the microcapsules, and the dissociation of the nucleic acid cross-linkers. The separation of duplex nucleic acid cross-linkers leads to low-stiffness hydrogel shells, allowing the release of loads. Switching off the light-induced plasmonic heating results in the regeneration of stiff hydrogel shells protecting the microcapsules, leading to the blockage of release processes. The thermoplasmonic release of tetramethylrhodamine-dextran, Texas Red-dextran, doxorubicin-dextran (DOX-D), or camptothecin-carboxymethylcellulose (CPT-CMC) from the microcapsules is introduced. By loading the microcapsules with two different drugs (DOX-D and CPT-CMC), the light-controlled dose release is demonstrated. Cellular experiments show efficient permeation of Au NPs/DOX-D or Au NRs/DOX-D microcapsules into MDA-MB-231 cancer cells and inefficient uptake by MCF-10A epithelial breast cells. Cytotoxicity experiments reveal selective thermoplasmon-induced cytotoxicity of the microcapsules toward MDA-MB-231 cancer cells as compared to MCF-10A cells. Also, selective cytotoxicity towards MDA-MB-231 cancer cells upon irradiation of the Au NPs- and Au NRs-functionalized microcapsules at λ = 532 or 910 nm is demonstrated.
关键词： doxorubicin,cytotoxicity,DNA nanotechnology,plasmon,switchable drug release
更新于2025-09-23 15:21:01
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Amine-functionalized, porous silica-coated NaYF4:Yb/Er upconversion nanophosphors for efficient delivery of doxorubicin and curcumin
摘要： Upconversion nanoparticles (UCNP) with unique multi-photon excitation photo-luminescence properties have been extensively explored as novel contrast agents for low-background biomedical imaging. There is an increasing interest in employing UCNPs as carrier for drug delivery as these offers a unique opportunity to combine therapy and diagnostics in one platform (theranostics). In the present work, we report microwave-assisted synthesis of hexagonal NaYF4:Yb/Er UCNPs coated with porous silica and functionalized with amine (UCNP@mSiO2). The UCNP@mSiO2 were investigated for controlled delivery of a chemotherapeutic agent, doxorubicin (DOX, hydrophilic), and a chemosensitizing agent, curcumin (CCM, hydrophobic). The drug loading was relatively higher for DOX (17.4%), in comparison to CCM (8.1%). The cumulative drug release from DOX-loaded UCNP@mSiO2 were 30 and 41% at physiological (7.4) and tumoral (6.4) pH, following a pseudo Fickian release pattern, whereas the release from CCM-loaded UCNP@mSiO2 were 27 and 50% at pH 7.4 and 6.4, following a non-Fickian and pseudo-Fickian release patterns. Both DOX and CCM-loaded UCNP@mSiO2 exhibited pH-dependent controlled drug delivery but the effect was more pronounced for CCM, the hydrophobic chemosensitizer. Cell viability assay using HeLa cells showed that DOX-loaded UCNP@mSiO2 inhibit cell growth in a dose-dependent manner, similar to free DOX, but the cell inhibition activity of free CCM was lower than CCM passively entrapped in UCNP@mSiO2. Confocal microscopy studies revealed cell uptake of both the drug by HeLa cells. Thus, UCNP@mSiO2 exhibited the unique capability to deliver hydrophilic and hydrophobic drugs, individually. UCNP@mSiO2 carrier, equipped with theranostic capabilities, may potentially be used for pH-responsive release of chemotherapeutic agents in cancer environment.
关键词： curcumin,porous silica,doxorubicin,drug delivery,Upconversion nanoparticles
更新于2025-09-23 15:21:01