Rational design of iridium–porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents

Near-infrared (NIR) emitters are important probes for biomedical applications. Nanoparticles (NPs) incorporating mono- and tetranuclear iridium(iii) complexes attached to a porphyrin core have been synthesized. They possess deep-red absorbance, long-wavelength excitation (635 nm) and NIR emission (720 nm). TD-DFT calculations demonstrate that the iridium–porphyrin conjugates herein combine the respective advantages of small organic molecules and transition metal complexes as photosensitizers (PSs): (i) the conjugates retain the long-wavelength excitation and NIR emission of porphyrin itself; (ii) the conjugates possess highly effective intersystem crossing (ISC) to obtain a considerably more long-lived triplet photoexcited state. These photoexcited states do not have the usual radiative behavior of phosphorescent Ir(iii) complexes, and they play a very important role in promoting the singlet oxygen (¹O₂) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high ¹O₂ generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC₅₀) (0.057 μM), excellent photothermal imaging and synergistic PDT and PTT under 635 nm laser irradiation. To our knowledge this is the first example of iridium–porphyrin conjugates as PSs for photothermal imaging-guided synergistic PDT and PTT treatment in vivo.

Iridium–porphyrin conjugates assembled in nanoparticles are photosensitizers that exhibit excellent photothermal imaging and synergistic PDT and PTT in vivo.     

D-A-D structured selenadiazolesbenzothiadiazole-based near-infrared dye for enhanced photoacoustic imaging and photothermal cancer therapy

Near-infrared (NIR) small molecular organic dyes as photothermal agents for cancer photothermal therapy (PTT) have attracted considerable research attention. Herein, two donor-acceptor-donor (D-A-D) structured NIR dyes, BBTT and SeBTT, are rationally designed, where the only difference is one heteroatom within the acceptor unit varying from sulfur to selenium (Se). More importantly, SeBTT NPs exhibit stronger NIR absorbance and higher photothermal conversion efficiency (PTCE ≈ 65.3%). In vivo experiments illustrate that SeBTT NPs can be utilized as a high contrast photoacoustic imaging (PAI) agent, and succeed in tumor suppression without noticeable damage to main organs under NIR photoirradiation. This study presents an effective molecular heteroatom surgery strategy to regulate the photothermal properties of NIR small molecules for enhanced PAI and PTT.     

铁掺杂的聚2-硝基-1,4-苯二胺纳米球的制备及在光热/光动力/化学动力学肿瘤治疗中的应用

肿瘤微环境(TME)的复杂性,使得单一治疗方式很难实现完全治愈。 为此,构建了一种负载吲哚菁绿(ICG)的铁掺杂的聚2-硝基-1,4-苯二胺多功能纳米球Fe-PNPD-ICG(FPIs),用于光热(PTT)/光动力(PDT)/化学动力学(CDT)的联合治疗。 在808 nm激光器照射下,ICG作为光敏剂可以产生单线态氧,铁掺杂的聚2-硝基-1,4-苯二胺纳米球作为光热剂具有36.65%的光热转换效率。 FPIs一旦内化到肿瘤内,由Fe³⁺/Fe²⁺转化引发Fenton反应产生·OH实现化学动力学治疗,反应过程中可以清除TME中过表达的谷胱甘肽(GSH),从而降低肿瘤中的抗氧化能力。 同时,产生的氧气可以改善TME中乏氧情况,增强PDT的治疗效果。 因此,FPIs是PTT/PDT/CDT联合治疗的一种理想材料,在肿瘤治疗中具有潜在的应用前景。     

Biodegradable Gold Nanovesicles with an Ultrastrong Plasmonic Coupling Effect for Photoacoustic Imaging and Photothermal Therapy

The hierarchical assembly of gold nanoparticles (GNPs) allows the localized surface plasmon resonance peaks to be engineered to the near‐infrared (NIR) region for enhanced photothermal therapy (PTT). Herein we report a novel theranostic platform based on biodegradable plasmonic gold nanovesicles for photoacoustic (PA) imaging and PTT. The disulfide bond at the terminus of a PEG‐b‐PCL block‐copolymer graft enables dense packing of GNPs during the assembly process and induces ultrastrong plasmonic coupling between adjacent GNPs. The strong NIR absorption induced by plasmon coupling and very high photothermal conversion efficiency (η=37 %) enable simultaneous thermal/PA imaging and enhanced PTT efficacy with improved clearance of the dissociated particles after the completion of PTT. The assembly of various nanocrystals with tailored optical, magnetic, and electronic properties into vesicle architectures opens new possibilities for the construction of multifunctional biodegradable platforms for biomedical applications.     

具有聚集诱导发光性质的近红外荧光染料

聚集诱导发光(AIE)现象的发现为解决传统有机荧光分子在高浓度和聚集形态下存在的荧光猝灭问题提供了最佳方案,并实现了在光电器件、化学传感、生物成像和靶向治疗等众多领域的广泛应用.随着对AIE 发光机理研究的不断深入,AIE 分子体系得到了极大的扩展.其中,一类具有给体-受体结构的AIE分子能够显著降低分子能隙,使发光分...     

Photothermal performance of MFe2O4 nanoparticles

In this paper, we synthesized three kinds of ferrites and investigated their photothermal property. The result indicated that the photothermal effect of Fe₃O₄ and MnFe₂O₄ nanoparticles declined while that of ZnFe₂O₄ nanoparticles maintained relatively stable after preservation for 70 days, and then ZnFe₂O₄ nanoparticles could effectively kill cancer cells under NIR laser.     

Ag@TiO2 Nanoprisms with Highly Efficient Near‐Infrared Photothermal Conversion for Melanoma Therapy

Melanoma is a primary reason of death from skin cancer and associated with high lethality. Photothermal therapy (PTT) has been developed into a powerful cancer treatment technique in recent years. Here, we created a low‐cost and high‐performance PTT agent, Ag@TiO₂ NPs, which possesses a high photothermal conversion efficiency of ≈65 % and strong near‐infrared (NIR) absorption about 808 nm. Ag NPs were synthesized using a two‐step method and coated with TiO₂ to obtain Ag@TiO₂ NPs by a facile sol‐gel method. Because of the oxide, Ag@TiO₂ NPs exhibit remarkable high photothermal conversion efficiencies and biocompatibility in vivo and in vitro. Cytotoxicity and therapeutic efficiency of photothermal cytotoxicity of Ag@TiO₂ NPs were tested in B16‐F10 cells and C57BL/6J mice. Under light irradiation, the elevated temperature causes cell death in Ag NPs‐treated (100 μg mL^?1) cells in vitro (both p<0.01). In the case of subcutaneous melanoma tumor model, Ag@TiO₂ NPs (100 μg mL^?1) were injected into the tumor and irradiated with a 808 nm laser of 2 W cm^?2 for 1 minute. As a consequence, the tumor volume gradually decreased by NIR laser irradiation with only a single treatment. The results demonstrate that Ag@TiO₂ NPs are biocompatible and an attractive photothermal agent for cutaneous melanoma by local delivery.     

Water-Soluble Fe(II) Complexes for Theranostic Application: Synthesis,Photoacoustic Imaging,and Photothermal Conversion

Significant effort focused on developing photoactivatable theranostics for localized image guided therapy of cancer by thermal ablation. In this context iron complexes were recently identified as photoactivatable theranostic agents with adequate biocompatibility and body clearance. Herein, a series of Fe^II complexes bearing polypyridine or N-heterocyclic carbenes is reported that rely on rational complex engineering to red-shift their MLCT based excited-state deactivation via a straightforward approach. The non-radiative decay of their MLCT upon irradiation is exploited for theranostic purposes by combining both tracking in photoacoustic imaging (PA) and photothermal therapy (PTT). The influence of structural modifications introduced herein on the solubility and stability of the complexes in biorelevant aqueous media is discussed. The relationship between complexes’ design, production of contrast in photoacoustic and photothermal efficiency are explored to develop tailored PA/PTT theranostic agents.     

A Water‐Soluble,NIR‐Absorbing Quaterrylenediimide Chromophore for Photoacoustic Imaging and Efficient Photothermal Cancer Therapy

Precision phototheranostics, including photoacoustic imaging and photothermal therapy, requires stable photothermal agents. Developing such agents with high stability and high photothermal conversion efficiency (PTCE) remains a considerable challenge. Herein, we introduce a new photothermal agent based on water‐soluble quaterrylenediimide (QDI) that can self‐assemble into nanoparticles (QDI‐NPs) in aqueous solution. Incorporating polyethylene glycol (PEG) into the QDI core significantly enhances both physiological stability and biocompatibility of QDI‐NPs. The highly photostable QDI‐NPs offer advantages including intense absorption in the near‐infrared (NIR) and high PTCE of up to 64.7±4 %. This is higher than that of commercial indocyanine green (ICG). Their small size (ca. 10 nm) enables sustained retention in deep tumor sites and also proper clearance from the body. QDI‐NPs allow high‐resolution photoacoustic imaging and efficient 808 nm laser‐triggered photothermal therapy of cancer in vivo.     

A Water‐Soluble,NIR‐Absorbing Quaterrylenediimide Chromophore for Photoacoustic Imaging and Efficient Photothermal Cancer Therapy

Precision phototheranostics, including photoacoustic imaging and photothermal therapy, requires stable photothermal agents. Developing such agents with high stability and high photothermal conversion efficiency (PTCE) remains a considerable challenge. Herein, we introduce a new photothermal agent based on water‐soluble quaterrylenediimide (QDI) that can self‐assemble into nanoparticles (QDI‐NPs) in aqueous solution. Incorporating polyethylene glycol (PEG) into the QDI core significantly enhances both physiological stability and biocompatibility of QDI‐NPs. The highly photostable QDI‐NPs offer advantages including intense absorption in the near‐infrared (NIR) and high PTCE of up to 64.7±4 %. This is higher than that of commercial indocyanine green (ICG). Their small size (ca. 10 nm) enables sustained retention in deep tumor sites and also proper clearance from the body. QDI‐NPs allow high‐resolution photoacoustic imaging and efficient 808 nm laser‐triggered photothermal therapy of cancer in vivo.     

Organic Nanoparticles with Persistent Luminescence for In Vivo Afterglow Imaging-Guided Photodynamic Therapy

Optical imaging-guided photodynamic therapy (PDT), with precise localization and non-invasive treatment of tumors, is an emerging technique with great potential for cancer therapy. However, impaired by tissue auto-fluorescence that causes low signal-to-background ratio (SBR), most fluorescence imaging systems show poor sensitivity to tumors in vivo. In this study, we synthesized organic nanoparticles (ONPs) with persistent luminescence and good biocompatibility for afterglow imaging-guided PDT. The ONPs displayed near-infrared light emission with half-life time at minute level, which offered high SBR and good tissue penetration for in vivo afterglow tumor imaging. Taking advantage of their abundant singlet oxygen generation by NIR laser irradiation guided to the tumor sites, the ONPs also enabled imaging-guided PDT for efficient suppression of tumor growth in mice with minimal damage to major organs.     

Algae Extraction Controllable Delamination of Vanadium Carbide Nanosheets with Enhanced Near‐Infrared Photothermal Performance

The two‐dimensional (2D) vanadium carbide (V₂C) MXene has shown great potential as a photothermal agent (PTA) for photothermal therapy (PTT). However, the use of V₂C in PTT is limited by the harsh synthesis condition and low photothermal conversion efficiency (PTCE). Herein, we report a completely different green delamination method using algae extraction to intercalate and delaminate V₂AlC to produce mass V₂C nanosheets (NSs) with a high yield (90 %). The resulting V₂C NSs demonstrated good structural integrity and remarkably high absorption in near infrared (NIR) region with a PTCE as high as 48 %. Systemic in vitro and in vivo studies demonstrate that the V₂C NSs can serve as efficient PTA for photoacoustic (PA) and magnetic resonance imaging (MRI)‐guided PTT of cancer. This work provides a cost‐effective, environment‐friendly, and high‐yielding disassembly approach of MAX, opening a new avenue to develop MXenes with desirable properties for a myriad of applications.     

Nanoscaled porphyrinic metal–organic framework for photodynamic/photothermal therapy of tumor

Nanoagents achieving photodynamic therapy (PDT) and photothermal therapy (PTT) combination treatment with improved therapeutic effect are highly desirable. However, the incorporation of both PDT and PTT into a single nanoagent often requires multistep fabrication process. Herein, we report that photoactive porphyrin ligands have been successfully introduced into Zn‐TCPP structure to construct the nanoagents that possesses photodynamic performance and photothermal performance simultaneously. Such a nanoagent enables the generation of single oxygen and heat under laser irradiation. Additionally, it exhibits satisfactory biocompatibility and high light toxicity against cancer cells. The current work provides a feasible approach to introduce both PDT and PTT into a single nanoplatform.     

A Single-wavelength NIR-triggered Polymer for in situ Generation of Peroxynitrite(ONOO~–) to Enhance Phototherapeutic Efficacy

Phototherapies including photodynamic therapy(PDT) and photothermal therapy(PTT) are the most promising and non-invasive cancer treatments. However, the efficacy of mono-therapy of PDT or PTT is often limited by the phototherapeutic defects such as low light penetration depth of photosensitizers and insufficiency of photothermal agents. Peroxynitrite(ONOO~-) has been proved to be an efficient oxidizing and nitrating agent that involves in various physiological and pathological processes. Therefore, ONOO~-produced in tumor site could be an effective treatment in cancer therapy. Herein, a novel cyanine dye-based(Cy7) polymer nanoplatform is developed for enhanced phototherapy by in situ producing ONOO~-. The Cy7 units in the nanoparticles can not only be served as the photosensitizer to produce reactive oxygen species(ROS) including singlet oxygen and superoxide anion for PDT, but also be used as a heat source for PTT and the release of NO gas from N-nitrosated napthalimide(NORM) at the same time. Since NO can react quickly with superoxide anion to generate ONOO~-, the enhanced phototherapy could be achieved by in situ ONOO~-produced by PCy7-NO upon exposure to the near infrared(NIR) light. Therefore, the NIRtriggered Cy7-based nanoplatform for ONOO~--enhanced phototherapy may provide a new perspective in cancer therapy.     

Single-atom engineering of hemicyanine and its amphiphilic derivative for optimized near infrared phototheranostics

Near-infrared (NIR) dyes are widely used in the field of in vivo phototheranostics. Hemicyanine dyes (HDs) have recently received tremendous attention due to their easy synthesis and excellent NIR features. However, HDs can easily form non-fluorescent aggregates and their potential for phototherapy still needs further exploration due to their poor ability to generate reactive oxygen species (ROS). Herein, a series of hemicyanine dyes with different chalcogen atom (O, S, Se) substitutions were constructed to achieve optimized potential for phototheranostics. By replacing O with the heavy atom Se in the xanthene skeleton, CySe-NEt₂ showed much more favourable features such as extended NIR absorption/emission wavelength, boosted ¹O₂ generation rate and higher photothermal effect. In addition, a poly(ethylene glycol) (PEG) group was introduced into the scaffold and yielded a nanotheranostic agent CySe-mPEG_5K, which easily formed nanoparticles with appealing features such as excellent photostability, effective prevention of unpleasant H-aggregation, fast/selective tumor accumulation and minimum dark toxicity. Solid tumor growth was significantly suppressed through combined photodynamic therapy (PDT) and photothermal therapy (PTT) guided by NIR fluorescence (NIRF) and photoacoustic (PA) imaging. This study not only presents the first example of selenium-substituted hemicyanine dyes, but also offers a reliable design strategy for the development of potent NIR phototheranostic agents with multi-mode imaging-guided combination therapeutic ability.

A selenium-substituted hemicyanine dye and its amphiphilic derivative were constructed as potent NIR phototheranostic agents with multi-mode imaging-guided combination therapeutic ability.     

HDAC6 inhibitor loaded bimetallene nanosheets with antagonizing thermoresistance for augmented mild photothermal therapy

Photothermal therapy(PTT) induces thermoresistance through cellular heat shock response, which impairs the therapeutic efficacy of the PTT. To resolve this problem, we developed a photothermal theranostics(denoted as PMH), which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6(HDAC6) selected inhibitor(ACY-1215), showing the synergistic antitumor effect both in vitro and in vivo. Mechanistically, under the photoacoustic imaging(PA) navigation, the relea...     

Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.     

Polymer materials for constructing therapeutical nanoparticles in photothermal therapy

Photothermal therapy (PTT) ablates tumors by thermal effects of photothermal agents (PTAs), and attracts wide attention due to the non-invasive characteristic. The ideal PTAs are expected to have high photothermal conversion effect under NIR irradiation, as well as targeting abilities and good biocompatibility satisfying the need of application in vivo. Nanoparticles (NPs) are commonly used as anti-tumor materials, and plenty of researches on therapeutical NPs for PTT treatment have been developed. Among various building blocks for photothermal NPs, polymer materials for biomedical applications have great advantages due to their negligible toxicity, flexibility for functional modification, and ability to integrate multiple therapeutic strategies. This review focuses on the polymer materials utilized in photothermal NP designing, including their application as excellent carriers and powerful PTAs with great PTT effects. Furthermore, the synergy therapy based on polymeric nanoplatform for enhancing PTT therapeutic efficiency will be introduced.     

One‐Dimensional Fe2P Acts as a Fenton Agent in Response to NIR II Light and Ultrasound for Deep Tumor Synergetic Theranostics

The stringent reaction conditions for an effective Fenton reaction (pH range of 3–4) hinders its application in cancer therapy. Therefore, how to improve the efficiency of the Fenton reaction in a tumor site has been the main obstacle in chemodynamic therapy (CDT). Herein, we report biocompatible one‐dimensional (1D) ferrous phosphide nanorods (FP NRs) with ultrasound (US)‐ and photothermal (PT)‐enhanced Fenton properties and excellent photothermal conversion efficiency (56.6 %) in the NIR II window, showing synergistic therapeutic properties. Additionally, the high photothermal conversion efficiency and excellent traverse relaxivity (277.79 mm ^?1 s^?1) of the FP NRs means they are excellent photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) agents. This is the first report on exploiting the response of metallic phosphides to NIR II laser (1064 nm) and ultrasound to improve the CDT effect with a high therapeutic effect and PA/MR imaging.     

Algae Extraction Controllable Delamination of Vanadium Carbide Nanosheets with Enhanced Near-Infrared Photothermal Performance

The two-dimensional (2D) vanadium carbide (V₂C) MXene has shown great potential as a photothermal agent (PTA) for photothermal therapy (PTT). However, the use of V₂C in PTT is limited by the harsh synthesis condition and low photothermal conversion efficiency (PTCE). Herein, we report a completely different green delamination method using algae extraction to intercalate and delaminate V₂AlC to produce mass V₂C nanosheets (NSs) with a high yield (90 %). The resulting V₂C NSs demonstrated good structural integrity and remarkably high absorption in near infrared (NIR) region with a PTCE as high as 48 %. Systemic in vitro and in vivo studies demonstrate that the V₂C NSs can serve as efficient PTA for photoacoustic (PA) and magnetic resonance imaging (MRI)-guided PTT of cancer. This work provides a cost-effective, environment-friendly, and high-yielding disassembly approach of MAX, opening a new avenue to develop MXenes with desirable properties for a myriad of applications.