Near-Infrared-Absorbing Diketopyrrolopyrrole-Based Semiconducting Polymer Nanoparticles for Photothermal Therapy

Photothermal therapy, an excellent therapeutic approach, has received much attention in recent years. Herein, a novel diketopyrrolopyrrole polymer (DPP-BDP) is prepared, which shows intense near-infrared (NIR) optical absorption and admirable photothermal conversion efficacy. Impressively, after assembly into nanoparticles (DB-FA), the as-prepared conjugated polymer demonstrates a uniformly distributed size around 200 nm with remarkable NIR absorption at 808 nm. Additionally, it displays high biocompatibility and photostability. More interestingly, the obtained DB-FA NPs are uptaken by cancer cells and present excellent anticancer in vitro and in vivo under 0.8 W cm⁻² or 1 W cm⁻² NIR laser irradiation, respectively. Hence, this work is expected to pave the way for using conjugated-polymer nanoparticles as a powerful photothermal agents for anticancer applications.     

Photothermal/Photodynamic Therapy with Immune‐Adjuvant Liposomal Complexes for Effective Gastric Cancer Therapy

A diagnosis and therapeutic strategy for gastric cancer is developed herein by combining thermosensitive liposomal (TSL)‐based photothermal/photodynamics therapy (PTT/PDT) with chemotherapy and adjuvant immunotherapy. IR820, a photothermal agent, paclitaxel (PTX), an antitumor drug, and imiquimod (R837), a Toll‐like‐receptor‐7 agonist, are coencapsulated into a TSL drug delivery system. These formed PTX‐R837‐IR820@TSL complexes exhibit excellent optical properties, good dispersibility, and stability. Under NIR light irradiation, the measurement of singlet oxygen production and thermal efficiency indicate promising potential of PTX‐R837‐IR820@TSL complexes for PTT and PDT. Confocal microscopy and small animal NIR imaging demonstrate tumor targeting ability of the liposomal complexes to gastric cancer cells. In vitro cell viability assays and in vivo animal experiments show prominent antitumor efficiency of PTX‐R837‐IR820@TSL complexes upon NIR light irradiation. This excellent therapeutic efficacy is attributed to the simultaneous chemotherapy and PTT/PDT. Furthermore, the liposomal complexes under NIR irradiation would ablate tumors to generate a pool of tumor‐associated antigens, which is able to promote strong antitumor immune responses in the presence of those R837‐containing liposomal complexes acted as adjuvant. These results indicate that the multifunctional liposomal complexes could realize a remarkable synergistic therapeutic outcome in gastric carcinoma.     

Synergistic Effect of Thermo‐Radiotherapy Using Au@FeS Core–Shell Nanoparticles as Multifunctional Therapeutic Nanoagents

Imaging guided combined therapy has attracted great attention in recent years. This study develops core–shell Au@FeS nanoparticles with polyethylene glycol (PEG) coating as multifunctional nanotheranostic agent for tumor imaging and combined photothermal therapy (PTT) and radiotherapy (RT). In this Au@FeS nanostructure, the gold core can act as a radiosensitizer for enhanced RT, while FeS shell offers contrast for T2‐weighted magnetic resonance imaging and endows the nanoparticles with strong high near‐infrared (NIR) for photoacoustic imaging and PTT. As demonstrated by both in vitro and in vivo experiments, Au@FeS‐PEG can act as excellent therapeutic agent for cancer synergistic treatment. More importantly, mild PTT boosts the blood flow into tumor and increases oxygenation to overcome the tumor hypoxia microenvironment, further enhancing the efficacy of RT. Moreover, Au@FeS‐PEG induces on obvious toxicity at a high dose (20 mg kg^?1) to the treated mice as evidenced by blood biochemistry. Therefore, this study brings an excellent strategy for cancer enhanced RT through NIR‐triggered mild PTT to overcome hypoxia‐associated radioresistance.     

Size and Shape Effects of Near-Infrared Light-Activatable Cu2(OH)PO4 Nanostructures on Phototherapeutic Destruction of Drug-Resistant Hypoxia Tumors

Development of simple, robust, and noninvasive therapeutic approaches to treat cancers and improve survival rates is a grand challenge in clinical biomedicine. In particular, the sizes and shape of the nanomaterials play a vital role in dictating their biodistribution and clearance pathways. It remains elusive how the size and shape of a nanomaterial affect its therapeutic efficacy in cancer diagnosis and treatments. To tackle the above problem, the effects of size and shape of Cu₂(OH)PO₄ nanostructures (nanosheets and quantum dots) on the photodynamic therapy (PDT) in destroying malignant drug-resistant lung tumors and on combating the tumor hypoxia problem are investigated and compared. The photocatalytic mechanism of Cu₂(OH)PO₄ nanostructures mainly involves the generation of reactive oxygen species (ROS), such as hydroxyl radical (^·OH) and singlet oxygen (¹O₂). Under an oxygen deprivation condition, Cu₂(OH)PO₄ nanosheets still can generate OH radicals to kill cancer cells upon near-infrared (NIR) light irradiation. Overall, in vitro and in vivo experiments show that Cu₂(OH)PO₄ nanosheets can overcome tumor hypoxia problems and effectively mediate dual modal PDT and photothermal therapeutic (PTT) effects on destruction of NCI-H23 lung tumors in mice using ultralow doses (350 mW cm⁻²) of NIR (915 nm) light.     

Multifunctional Small Molecule Fluorophore for Long‐Duration Tumor‐Targeted Monitoring and Dual Modal Phototherapy

In this work, a specific tumor‐targeted small molecular fluorophore for synchronous long‐duration cancer imaging, photodynamic therapy, and photothermal therapy is synthesized. This novel fluorophore exhibits specific targeting ability in certain tumors (U87MG, MDA‐MB‐231, A549, etc.) based on its inherent structure and efficiently generates local hyperthermia and reactive oxygen species simultaneously for imaging‐guided precise cancer therapy combining the photothermic and photodynamic effects under laser irradiation. Meanwhile, compared to traditional near infrared fluorophore, this novel fluorophore with significantly enhanced stability against photobleaching can prolong the time of tumor imaging and improve the phototherapy efficiency. This work presents a potential strategy to develop small‐molecule‐based cancer theranostic agents for simultaneous cancer targeting, imaging, and therapy.     

Core–Shell Bi2Se3@mSiO2‐PEG as a Multifunctional Drug‐Delivery Nanoplatform for Synergistic Thermo‐Chemotherapy with Infrared Thermal Imaging of Cancer Cells

Thermo‐chemotherapy combining photothermal therapy (PTT) with chemotherapy has become a potent approach for antitumor treatment. In this study, a multifunctional drug‐delivery nanoplatform based on polyethylene glycol (PEG)‐modified mesoporous silica‐coated bismuth selenide nanoparticles (referred to as Bi₂Se₃@mSiO₂‐PEG NPs) is developed for synergistic PTT and chemotherapy with infrared thermal (IRT) imaging of cancer cells. The product shows no/low cytotoxicity, strong near‐infrared (NIR) optical absorption, high photothermal conversion capacity, and stability. Utilizing the prominent photothermal effect, high‐contrast IRT imaging and efficient photothermal killing effect on cancer cells are achieved upon NIR laser irradiation. Moreover, the successful mesoporous silica coating of the Bi₂Se₃@mSiO₂‐PEG NPs cannot only largely improve the stability but also endow the NPs high drug loading capacity. As a proof‐of‐concept model, doxorubicin (DOX) is successfully loaded into the NPs with rather high loading capacity (≈50.0%) via the nanoprecipitation method. It is found that the DOX‐loaded NPs exhibit a bimodal on‐demand pH‐ and NIR‐responsive drug release property, and can realize effective intracellular drug delivery for chemotherapy. The synergistic thermo‐chemotherapy results in a significantly higher antitumor efficacy than either PTT or chemotherapy alone. The work reveals the great potential of such core–shell NPs as a multifunctional drug‐delivery nanosystem for thermo‐chemotherapy.     

Obviously Enhanced Fluorescent Signal of Core-Shell Nanostructures through Simultaneous Regulation of Spectral Overlap and Shell Thickness for Imaging and Photothermal Therapy of Ovarian Cancer Cells

In this research, by simultaneously regulating the two major factors affecting the plasmonic enhanced fluorescence (PEF), spectral overlap and the distance between the fluororophores and the noble metal nanoparticles, a significantly enhanced fluorescent signal is achieved. Core-shell nanostructures composed of aspect ratio (AR) adjustable gold nanorods (GNRs) and various thickness of SiO₂ are prepared and the decorated fluorophores are realized optimized PEF. A typical stimuli-responsive conjugated polymer, polydiacetylene (PDA), and a near-infrared (NIR) dye Cy5.5 are selected as fluorophores and their fluorescent signal are enhanced 7.26 and 4.41 times, respectively. Based on the optimized optical properties, a multifunctional antibody modified Mab-Cy5.5-GNRs@SiO₂ is successfully demonstrated the targeting, imaging, and photothermal therapy (PTT) effects on SKOV-3 ovarian cancer cells.     

Radionuclide 188Re-Loaded Photothermal Hydrogel for Cancer Theranostics

Herein, an injectable photothermal hydrogel system containing a therapeutic radionuclide ¹⁸⁸Re is studied for combined radioisotope therapy and photothermal therapy (PTT) of cancer. A dopamine-conjugated poly(α,β-aspartic acid) copolymer (PDAEA) is used to trigger a sol–gel phase transition in mixture with Fe³⁺ ions, rapidly forming a gel by simply mixing PDAEA and FeCl₃ phosphate buffer saline solutions. The injectable hydrogel exhibits strong near-infrared light absorbance and can efficiently convert light into a heating effect for local PTT treatment. The obtained hydrogel possesses a porous 3D microstructure, and can be utilized for radionuclide loading. After the Na¹⁸⁸ReO₄ loading, the hydrogel is intratumorally injected into the tumor of mice bearing 4T1 murine breast cancer cells for studying the tumor retention and therapeutic efficiency. In vivo results show that Na¹⁸⁸ReO₄-loaded hydrogel exhibits significantly longer time in the tumor sites than that of free Na¹⁸⁸ReO₄. The tumor growth of mice treated with Na¹⁸⁸ReO₄-loaded hydrogel under near-infrared radiation is significantly inhibited compared with control groups. Therefore, the results show that the developed strategy using an injectable and biocompatible hydrogel may promote the applications of radioisotope therapy and photothermal therapy for cancer.     

金纳米星诊疗剂的光热特性及其在光热治疗和光学相干层析成像中的应用研究

为了开发一种优异的用于光热治疗和光学相干层析成像的金纳米星诊疗剂,对金纳米星的制备、光热特性以及光热治疗和光学相干层析成像中的应用进行研究.利用尖端结构增强金纳米材料的局域表面等离子体共振特性,通过种子介导法制备了多枝化的金纳米星,多尖端的结构使其具有明显的光热效果,并探究了其作为光热治疗的诊疗剂和光学相干层析成像造影...     

Rapid Clearance of IR783 and Methyl-β-cyclodextrin Complex for Improved Tumor Imaging

Near-infrared (NIR) fluorescence cancer imaging with targeted NIR fluorophores holds considerable promise for accurate detection and cancer diagnosis. Among the various NIR heptamethine cyanine dyes reported previously, IR783 as a single small molecule has been widely used for tumor-targeted imaging without the additional conjugation of targeting moieties. Despite the potential advantages of IR783, the major problems, such as its non-specific uptake in normal tissues/organs and slow clearance, remain to be solved. A key determinant of sensitivity and detectability in tumor imaging is the improvement of the tumor-to-background ratio (TBR). Herein, a simple and effective supramolecular complex self-assembled from IR783 and methyl-β-cyclodextrin is developed to improve tumor imaging accompanied by rapid clearance from the body. The IR783-cyclodextrin complex allowed for rapid whole body biodistribution, which remarkably reduced non-specific background uptake, and thus increased the TBR value within 24 h post-injection. Therefore, this strategy is applicable in combination with many different types of carbocyanine dyes for improved tumor imaging.     

Synergistic Effect of Photothermal Therapy and Chemotherapy Using Camptothecin‐Conjugated Gold Nanorods

A combinatorial treatment comprising thermal therapy and chemotherapy offers synergistic effects by inducing localized heat to targeted tumor sites and simultaneously delivering anticancer drugs to minimize systemic side effects and enhance the cytotoxic effect. In this study, a novel platform is developed for combining photothermal therapy and chemotherapy using drug‐conjugated gold nanorods (GNRs). Camptothecin (CPT), a model anticancer drug, is chemically conjugated onto GNRs through hydrolytic ester bonding. Upon near‐infrared (NIR) irradiation, localized heat from GNRs in target areas starts to destroy tissues and cells via photothermal therapy, and the elevated temperature accelerates hydrolysis of ester linkage, rapidly releasing drugs for chemotherapy. This combined NIR triggered thermal therapy and chemotherapy with CPT‐functionalized GNRs (CPT‐GNRs) presents a synergistic effect that has high efficacy in in vitro tests, thus providing a robust platform for efficient cancer treatments.     

Tumor‐Targeting W18O49 Nanoparticles for Dual‐Modality Imaging and Guided Heat‐Shock‐Response‐Inhibited Photothermal Therapy in Gastric Cancer

Photothermal therapy (PTT) is an emerging noninvasive and precise localized therapeutic modality; however, it is deeply limited by its poor tumor accumulation, inadequate photothermal conversion efficiency, and the thermoresistance of cancer cells. Aimed at these shortcomings, tumor‐targeting nanoparticles (iRGD‐W₁₈O₄₉‐17AAG) comprising carboxyl‐group‐functionalized W₁₈O₄₉ nanoparticles, integrin‐targeting peptide iRGD, and HSP90‐inhibitor 17AAG are developed. The W₁₈O₄₉ nanoparticles act as excellent PTT carriers and computed tomography (CT) imaging contrast agents. The ring type polypeptide iRGD promotes the accumulation of nanoparticles in the tumour and further penetration into cancer cells. The introduction of 17AAG can inhibit the heat‐shock response and overcome the thermoresistance, thus increasing the curative effect of PTT and reducing the chance of tumor recurrence. The W₁₈O₄₉ nanoparticles can also be used to monitor and guide the phototherapeutic through CT and near‐infrared fluorescence imaging after modification with Cy5.5. In addition, superior biosafety is also indicated in both preliminary in vitro and in vivo assessments. The potential of iRGD‐W₁₈O₄₉‐17AAG in tumor targeting, dual modality imaging‐guided and remarkable enhanced PTT of gastric cancer with ignorable side effect both in vitro and in vivo, which may be further applied in clinic, is highlighted.     

Monodisperse Polypyrrole Nanoparticles Prepared via γ‐Ray Radiolysis of Water: An Efficient Near‐Infrared Photothermal Agent for Cancer Therapy

Biosafe nanoparticles with strong near‐infrared (NIR) light photothermal conversion effect can bring effective hyperthermia as one of the promising approaches in cancer therapy. In this work, a new facile and green preparation method of polypyrrole (PPy) nanoparticles based on ⁶⁰Co γ‐ray radiation on a simple air‐saturated strong acidic aqueous solution of pyrrole (pH ≤ 1) is studied. According to the MCAP‐FACSIMILE simulation on the concentrations of the radiolysis products of water at the presence of H⁺ and O₂, the main strong oxidative radiolysis products · OH and H₂O₂ rapidly induce the polymerization of pyrrole. The size of the prepared PPy nanoparticles is about several tens of nanometers and can be controlled by the pH, the concentration of the stabilizer poly(vinyl alcohol), and the absorbed dose rate (the amount of energy absorbed per unit mass of the irradiated material within per unit of time). The PPy nanoparticles show rapid and remarkable NIR (808 nm) photothermal conversion efficiency up to 40.1% in water. Furthermore, the in vitro and in vivo experiments confirm that the prepared PPy nanoparticles exhibit enough strong NIR photothermal effect in tumor cells (4T1 and HeLa) and show a promising prospect as the NIR photothermal agent for the future cancer therapy.     

Human‐Serum‐Albumin‐Coated Prussian Blue Nanoparticles as pH‐/Thermotriggered Drug‐Delivery Vehicles for Cancer Thermochemotherapy

Constructing novel multimodal antitumor therapeutic nanoagents has attracted tremendous recent attention. In this work, a new drug‐delivery vehicle based on human‐serum‐albumin (HSA)‐coated Prussian blue nanoparticles (PB NPs) is synthesized. It is demonstrated that doxorubicin (DOX)/HSA is successfully loaded after in situ polymerization of dopamine onto PB NPs, and the PB@PDA/DOX/HSA NPs are highly compatible and stable in various physiological solutions. The NPs possess strong near‐infrared (NIR) absorbance, and excellent capability and stability of photothermal conversion for highly efficient photothermal therapy applications. Furthermore, a bimodal on‐demand drug release sensitively triggered by pH or NIR irradiation has been realized, resulting in a significant chemotherapeutic effect due to the preferential uptake and internalization of the NPs by cancer cells. Importantly, the thermochemotherapy efficacy of the NPs has been examined by a cell viability assay, revealing a remarkably superior synergistic anticancer effect over either monotherapy. Such multifunctional drug‐delivery systems composed of approved materials may have promising biomedical applications for antitumor therapy.     

Highly Ligand‐Directed and Size‐Dependent Photothermal Properties of Magnetite Particles

The development of cancer photothermal therapies, many of which rely on photothermal agents, has received significant attention in recent years. In this work, various ligands‐stabilized magnetite (Fe₃O₄) particles are fabricated and utilized as a photothermal agents for in vivo tumor‐imaging‐guided photothermal therapy. Fe₃O₄ particles stabilized by macromolecular ligands as, e.g. polyethylene glycol (PEG), exhibit a superior and more stable photothermal effect compared to Fe₃O₄ particles stabilized by small molecules like citrate, due to their stronger ability of antioxidation. In addition, the photothermal effect of Fe₃O₄ particles is revealed to increase with size, which is attributed to the redshift of Vis‐NIR spectra. Fe₃O₄ particles injected intravenously into mice can be accumulated in the tumor by the application of an external magnetic field, as revealed by magnetic resonance imaging. In vivo photothermal therapy test of PEG‐stabilized Fe₃O₄ further achieves better tumor ablation effect. Overall, this study demonstrates efficient imaging‐guided photothermal therapy of cancer that is based on Fe₃O₄ particles of optimized size and with optimized ligands. It is expected that the ligand‐directed and size‐dependent photothermal effect will provide more approaches in the design of novel materials.     

银纳米链状材料的制备及近红外吸收性质

报道了利用水/油相界面反应,采用湿化学法合成银纳米链状材料的方法,并对这种材料的近红外吸收性质和光热转换性质进行了研究。TEM分析表明,银纳米材料为链状结构,直径约为50nm,长度分布范围较宽,从几十纳米至几百纳米。这种材料具有强的近红外吸收特性,随着还原剂加入量的增加,吸收带逐渐展宽(800～1300nm),而且平坦。这种材料具有优异光热转换性质,一经808nm激光照射,温度迅速提高。该材料优异的近红外吸收和光热转换性质,使其在红外断层成像和近红外热疗等领域具有广阔的应用前景。     

In vitro and in vivo comparative study of the phototherapy anticancer activity of hyaluronic acid-modified single-walled carbon nanotubes,graphene oxide,and fullerene

In this work, carbon nanomaterials, single-walled carbon nanotubes (SWNT), graphene oxide (GO), and fullerene (C60) were modified by hyaluronic acid (HA) to obtain water-soluble and biocompatible nanomaterials with high tumor-targeting capacity and then the comparative study of these hyaluronic acid-modified carbon nanomaterials was made in vitro and in vivo. The conjugates of hyaluronic acid and carbon nanomaterials, namely, HA-SWNT, HA-GO, HA-C60, were confirmed by UV/Vis spectrum, Fourier transform infrared spectroscopy (FTIR), and a transmission electron microscope (TEM). After HA modification, the sizes of HA-SWNT, HA-GO, and HA-C60 were in a range of 70 to 300 nm, and all the three HA-modified materials were at negative potential, demonstrating that HA modification was in favor of extravasation of carbon materials into a tumor site due to enhanced permeability and retention effect of tumor. Photothermal conversion in vitro test demonstrated excellent photothermal sensitivity of HA-SWNT and HA-GO. But the reactive oxygen yield of HA-C60 was the highest compared with the others under visible light irradiation, which proved the good photodynamic therapy effect of HA-C60. In addition, cytotoxicity experiments exhibited that the inhibitory efficacy of HA-SWNT was the lowest, the second was HA-C60, and the highest was HA-GO, which was consistent with the uptake degree of them. While under the laser irradiation, the cell inhibition of the HA-SWNT was the highest, the second was HA-GO, and the last was HA-C60. In vivo evaluation of the three targeting carbon nanomaterials was consistent with the cytotoxicity assay results. Taken together, the results demonstrated that HA-SWNT and HA-GO were suited for photothermal therapy (PTT) agents for their good photothermal property, while HA-C60 was used as a kind of photodynamic therapy (PDT) agent for its photodynamic effect.     

Hydrophilic Cu3BiS3 Nanoparticles for Computed Tomography Imaging and Photothermal Therapy

Hydrophilic Cu₃BiS₃ nanoparticles (NPs) have been prepared using the thermal decomposition of precursor complexes in oily‐mixed solvent followed by coating the produced Cu₃BiS₃ NPs with polyvinylpyrrolidone (PVP). The resulting Cu₃BiS₃/PVP NPs remain stable in aqueous solutions over a long period of time, and meanwhile, they show low in vitro cytotoxicity and negligible toxicity to mice in vivo. Cu₃BiS₃/PVP NPs could operate as an efficient dual‐modal contrast agent to simultaneously enhance X‐ray computed tomography imaging and photothermal imaging of tumor model in vivo. Moreover, highly efficient ablation of cancer cells both in vitro and in vivo has been successfully achieved by combining Cu₃BiS₃/PVP NPs with near‐infrared (NIR) laser irradiation. All of the positive results in this study highlight that Cu₃BiS₃/PVP NPs could serve as a promising platform for cancer diagnosis and therapy.     

PEGylated polyethylenimine-stabilized polypyrrole nanoparticles loaded with DOX for chemo-photothermal therapy of cancer cells

Combination of kinds of therapy modalities is promising for effective cancer treatment. Herein, a kind of multifunctional nanoparticles (NPs) was developed for cancer chemo-photothermal therapy applications. Polypyrrole (PPy) NPs were formed using a facile polymerization method using poly(ethyleneimine) (PEI) as stabilizer, followed by polyethylene glycol (PEG) modification and anticancer drug doxorubicin (DOX) loading. Showing obvious absorbance in the NIR range, the obtained PPy-PEI-PEG NPs displayed well photothermal ability with desirable photothermal stability. The release of the loaded DOX can be promoted by pH and laser stimulation. Compared with single therapy modality, the combination of chemotherapy and photothermal therapy showed higher cancer cell killing effect. The cellular internalization of the obtained NPs was proved to be effective. The developed multifunctional NPs are promising candidates for combined therapy of cancer cells.     

近红外光热转换纳米晶研究进展

近红外光热转换纳米晶材料因其在近红外区(普遍位于780~1 400 nm)的高效光热转换性能,已广泛应用于光热杀死癌细胞、肿瘤治疗、海水淡化等领域。因其多样的液相制备方法和形貌控制、纳米结构复合、逐渐提高的光热转换效率以及表面易于药物修饰等优点,该材料在光热成像诊断、光热治疗等领域引起了学术界的广泛关注。本文综述了近红外光热转换纳米晶的研究进展,主要包括贵金属纳米晶、铜硫族半导体纳米晶、碳相关纳米晶以及这些纳米晶材料构成的复合结构,同时介绍了具有较高光热转换效率的表面等离子体共振(SPR)材料的研究进展,尤其是双模态SPR性质的耦合在光热转换领域的应用前景。基于其性能协同耦合的特性,双模态表面等离子体共振耦合的复合纳米晶将是近几年光热转换纳米晶发展的重要方向。