- 标题
- 摘要
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- 实验方案
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Multifunctional Thermosensitive Liposomes Based on Natural Phase Change Material: Near-Infrared Light-Triggered Drug Release and Multimodal Imaging Guided Cancer Combination Therapy
摘要： Multifunctional theranostic nanoplatforms (NPs) in response to environment stimulations for on-demand drug release are highly desirable. Herein, the near-infrared (NIR)-absorbing dye, indocyanine green (ICG) and the antitumor drug, doxorubicin (DOX) were efficiently co-encapsulated into the thermosensitive liposomes based on natural phase change material (PCM). Folate and conjugated gadolinium chelate-modified liposome shells enhance active targeting and magnetic resonance (MR) performance of the NPs while maintaining the size of the NPs. The ICG/DOX loaded and gadolinium chelates conjugated temperature-sensitive liposomes nanoplatforms (ID@TSL-Gd NPs) exhibited NIR-triggered drug release and prominent chemo-, photothermal, photodynamic therapy properties. With the co-encapsulated ICG, DOX and the conjugated gadolinium chelates, the ID@TSL-Gd NPs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging, FL/PAI/MRI) guided combination tumor therapy (chemotherapy, photothermotherapy and photodynamic therapy, Chemo/PTT/PDT). After tail vein injection, the ID@TSL-Gd NPs accumulated effectively in subcutaneous HeLa tumor of mice. The tumor was effectively suppressed by accurate imaging guided NIR triggered phototherapy and chemotherapy, and no tumor regression and side effects were observed. In summary, the prepared ID@TSL-Gd NPs achieved multimodal imaging-guided cancer combination therapy, providing a promising platform for improving diagnosis and treatment of cancer.
关键词： Multimodal imaging,Liposomes,Thermosensitive,Combination therapy,Phase change material
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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Prussian blue nanosphere-embedded in situ hydrogel for photothermal therapy by peritumoral administration
摘要： To establish an injectable hydrogel containing prussian blue (PB) nanospheres for photothermal therapy against cancer, PB nanospheres were prepared by one-pot synthesis and the thermosensitive Pluronic F127 was used as the hydrogel matrix. The PB nanospheres and the hydrogel were characterized by shape, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation, as well as the rheological features. The effect of the PB nanospheres and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in a tumor-bearing mouse model. The PB nanospheres had a diameter of about 150 nm and exhibited satisfactory serum stability, photo-heat convert ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanosphere-containing hydrogel showed a phase transition at body temperature and, as a result, a long retention time in vivo. The photothermal agent-embedded hydrogel displayed promising photothermal therapeutic effects in the tumor-bearing mouse model with little-to-no systemic toxicity after peritumoral administration.
关键词： PB,In situ,Thermosensitive,Hydrogel,Photothermal,Injectable,Nanospheres
更新于2025-09-23 15:23:52
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Photo-Controlled Thermosensitive Electrochemiluminescence Hydrogel for Isocarbophos Detection
摘要： Endowing specificity and controllability with the electrochemiluminescence (ECL) thermosensitive hydrogels is vitally crucial to expand their sensing applications. Herein, a novel photo-controlled thermosensitive electrochemiluminescence hydrogel (PT-ECL hydrogel) sensing platform with sufficient simplicity, specificity and precise controllability, for the first time, is proposed, by the integration of Ru(bpy)3 2+ derivatives (signal reporter), split aptamers (recognition unites), and Au nanorods (AuNRs) (photothermal energy converter) into the poly(N-isopropylacrylamide) (pNIPAM) matrix. In the presence of the model target isocarbophos (ICP), the conjugation of two split-aptamers initiated the ECL-Resonance Energy Transfer (ECL-RET) between the Au nanorods and the Ru(bpy)3 2+ centers. Surprisingly, under the irradiation of near-infrared (NIR) light, the photothermal effect of AuNRs prompted the shrinkage of the hydrogel, resulting in the enhancement of the ECL-RET and further ~7 times signal amplification. Consequently, the PT-ECL hydrogel sensing platform performed well for ICP detection with a low detection limit of 20 pM (S/N=3) and wide linear range from 50 pM to 4 μM, with great stability and repeatability. Obviously, the results showed that AuNRs utilized in this paper served the role as not only the ECL-RET acceptor, but also the photothermal converter to prompt the phase change of the PT-ECL hydrogel precisely and simply controlled by NIR light. Use of the proposed PT-ECL hydrogel detection scheme is a first step toward enabling a newly upgraded highly sensitive, selective hydrogel-based assays and also paving way for the application of smart photothermal reagents.
关键词： split aptamers,Au nanorods,photo-controlled,electrochemiluminescence,isocarbophos detection,thermosensitive hydrogel
更新于2025-09-23 15:19:57
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Fluorescent 2-(pyridin-2-yl)vinyl pyridine dyes and their thermo-controlled release
摘要： The generation of unique thermosensitive fluorescent dyes via heteroaromatic Heck cross-coupling and N-pyridin-2-yl nucleophilic substitution was described. To demonstrate thermosensitive properties, the precursor was converted into carbonate or phosphate and heating at various temperatures and times of heating. Significant changes in fluorescence intensity and emission wavelengths, between carbonates and the cyclic product, were observed and proved that dyes may serve as removable fluorescent labels with large Stokes shifts (>80 nm). Application of thermosensitive fluorescent dyes in oligonucleotide labelling has been demonstrated.
关键词： Heck cross-coupling,large Stokes shifts,N-pyridin-2-yl nucleophilic substitution,thermosensitive fluorescent dyes,oligonucleotide labelling
更新于2025-09-16 10:30:52
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A ruthenium nitrosyl-functionalized magnetic nanoplatform with near-infrared light-controlled nitric oxide delivery and photothermal effect for enhanced antitumor and antibacterial therapy
摘要： Developing spatiotemporal-controlled nitric oxide (NO) delivery nanoplatform is highly desirable for its biological applications as tumor inhibitor and antibacterial agent. In this study, a novel multifunctional magnetic nanoplatform {Fe3O4@PDA@Ru-NO@FA} (1) was developed for the near-infrared (NIR) light-controlled release of NO, in which a ruthenium nitrosyl (Ru-NO) donor and folic acid (FA)-directing group were covalently functionalized onto Fe3O4@PDA. Nanoplatform 1 preferentially accumulated in folate receptor-overexpressing cancer cell lines and magnetic field-guided tumor tissue, instantly released NO, and simultaneously produced a prominent photothermal effect upon 808 nm NIR light irradiation, leading to remarkable in vitro and in vivo antitumor efficacy. When nanoplatform 1 was treated only once, the potential MRI contrast agent was sufficient to significantly inhibit or eliminate the tumor tissues in living mice, thus offering opportunities for future NO-involved multimodal cancer therapy. In addition, a NO delivery nanoplatform {Fe3O4@PDA@Ru-NO} was imbedded in the matrix of chitosan (CS)-poly(vinyl alcohol) (PVA) material to develop a hybrid thermosensitive CS-PVA/NO hydrogels. The CS-PVA/NO hydrogels demonstrated mild (<150 mW cm-2) NIR light-controlled NO delivery and thus produced efficient antibacterial effect for both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Therefore, these hydrogels feature potential as antibacterial dressings for treating wound bacterial infection.
关键词： nitric oxide delivery,magnetic nanoplatform,ruthenium nitrosyl donor,antitumor and antibacterial therapy,thermosensitive hydrogel
更新于2025-09-12 10:27:22
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Highly cooperative fluorescence switching of self-assembled squaraine dye at tunable threshold temperatures using thermosensitive nanovesicles for optical sensing and imaging
摘要： Thermosensitive fluorescent dyes can convert thermal signals into optical signals as a molecular nanoprobe. These nanoprobes are playing an increasingly important part in optical temperature sensing and imaging at the nano- and microscale. However, the ability of a fluorescent dye itself has sensitivity and accuracy limitations. Here we present a molecular strategy based on self-assembly to overcome such limitations. We found that thermosensitive nanovesicles composed of lipids and a unique fluorescent dye exhibit fluorescence switching characteristics at a threshold temperature. The switch is rapid and reversible and has a high signal to background ratio (>60), and is also highly sensitive to temperature (10–22%/°C) around the threshold value. Furthermore, the threshold temperature at which fluorescence switching is induced, can be tuned according to the phase transition temperature of the lipid bilayer membrane forming the nanovesicles. Spectroscopic analysis indicated that the fluorescence switching is induced by the aggregation-caused quenching and disaggregation-induced emission of the fluorescent dye in a cooperative response to the thermotropic phase transition of the membrane. This mechanism presents a useful approach for chemical and material design to develop fluorescent nanomaterials with superior fluorescence sensitivity to thermal signals for optical temperature sensing and imaging at the nano- and microscales.
关键词： fluorescence switching,optical sensing,nanovesicles,thermosensitive fluorescent dyes,imaging
更新于2025-09-11 14:15:04
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Hybridization of graphene oxide into nanogels to acquire higher photothemal effects for therapeutic delivery
摘要： Although the special architecture of two-dimensional (2D) nanomaterials endows them with unique properties, their poor colloidal stability remains a main bottleneck to fully exploit their applications in the biomedical field. Herein, this study aims to develop a simple and effective approach to in situ incorporate 2D graphene oxide (GO) nanopletlets into thermosensitive matrix to acquire hybrid nanogels with good stability and photothermal effect. In order to improve its stability, GO firstly underwent silanization to its surface with double bonds, followed by intercalation with N-isopropylacrylamide (NIPAM) in the presence of disulfide-containing crosslinker via an emulsion method. Radical polymerization was then initiated to accelerate direct GO exfoliation in PNIPAM nanogels by forming covalent bonds between them. The well-dispersed GO nanopletlets in the nanogels not only displayed an enhanced photothermal effect, but also improved the encapsulation efficiency of an anticancer drug. The hybrid nanogels accelerate drug release under conditions mimicking the acidic/reducible solid tumor and intracellular microenvironments, most importantly, it can be further enhanced via remote photothermal treatment. The multifunctional nanogels potentiate their synergistic anticancer bioactivity as an ideal nanoplatform for cancer treatment.
关键词： Graphene Oxide,Anticancer Drug Delivery,Photothermal Effect,Silanization,Thermosensitive Nanogels
更新于2025-09-04 15:30:14
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Enhanced photo/chemo combination efficiency against bladder tumor by encapsulation of DOX and ZnPC into in situ-formed thermosensitive polymer hydrogel
摘要： Background: Chemotherapy after transurethral resection is commonly recommended for bladder cancer. However, studies have shown that chemotherapy solely can hardly decrease progression rates of bladder cancer. The combination of chemotherapeutic agents with photodynamic therapy (PDT), a new promising localized therapy, may become a workable strategy for combating bladder cancer. This study reports the combination of doxorubicin (DOX)-based chemotherapy and zinc phthalocyanine (ZnPC)-based PDT using in situ-formed thermal-responsive copolymer hydrogel. Materials and methods: The copolymer was synthesized by polymerization of 3-caprolactone, 1,4,8-trioxa[4.6]spiro-9-undecanone and poly(ethylene glycol) and was abbreviated as PCL-PTSUO-PEG. The thermal-responsive nanoparticles (TNPs) were prepared by the nanoprecipitation technology. The thermal-responsive hydrogel was formed after 37°C heating of TNP solution. The size, morphology and dynamic viscosity of hydrogel were detected. The in vitro drug release profile of TNP/DOX/ZnPC was performed. Cell uptake, cell inhibition and ROS generation of TNP/DOX/ZnPC were studied in 5637 cells. The in vivo antitumor activity of TNP/DOX/ZnPC was evaluated in nude mice bearing 5637 cells xenograft. Results: TNP/DOX and TNP/ZnPC had an average diameter of 102 and 108 nm, respectively. After being heated at 37°C for 5 minutes, TNP/DOX and TNP/ZnPC solution turned uniform light red and dark green hydrogel. ZnPC encapsulation designed by TNP could significantly improve its aqueous solubility to 1.9 mg/mL. Cell inhibition showed that the best cell inhibition was found, with cell viability of 18.5%, when the weight ratio of DOX and ZnPC encapsulated in the TNP reached about 1:5. TNP/DOX/ZnPC generated relative high level of ROS with 4.8-fold of free ZnPC and 1.6-fold of TNP/ZnPC. TNP/DOX/ZnPC showed only 8-fold of relative tumor growth without obvious toxicity to the mice. Conclusion: Thermosensitive thermal-responsive hydrogel reported in this contribution are promising in situ-formed matrix for DOX- and ZnPC-based photo/chemo combination treatment for bladder cancer therapy.
关键词： chemotherapy,photodynamic therapy,thermosensitive,bladder cancer,combination therapy,hydrogel
更新于2025-09-04 15:30:14