Efficient Photothermal Therapy Research Articles

Multi-responsive cascade enzyme-like catalytic nanoassembly for ferroptosis amplification and nanozyme-assisted mild photothermal therapy

Ferroptosis is greatly restricted by low reactive oxygen species (ROS) generation efficiency, and the inherent self-protection mechanism originating in heat shock proteins (HSPs) seriously impedes the efficiency of photothermal therapy (PTT). Herein, we designed an intelligent strategy utilizing cascade catalytic nanoassemblies (Au@COF@MnO2) with triple-enzyme activity for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. Gold nanozyme was encapsulated within a hollow manganese dioxide (MnO2) shell with the help of covalent organic frameworks (COFs). The nanoassemblies possess the ability of photothermal conversion. Mechanism studies suggested that glutathione (GSH) depletion by Au@COF@MnO2 leads to the inactivation of glutathione peroxidase 4 (GPX4). This effect synergized with Mn2+-mediated reactive oxygen species (ROS) generation to enhance the accumulation of lipid peroxide (LPO), thereby inducing high-efficiency ferroptosis. Notably, gold nanozyme facilitated the conversion of glucose into gluconic acid and hydrogen peroxide (H2O2). This process augmented the endogenous H2O2 levels necessary for Fenton chemistry, which could effectively promote the generation of ROS. Simultaneously, glucose depletion downregulated the expression of HSPs induced by hyperthermia, consequently reducing cellular heat resistance for enhancing PTT. Therefore, the cascade catalytic nanoassembly not only exhibits high tumor inhibition and admirable biosafety, but also possesses trimodal imaging performance for imaging-guided tumor therapy in vivo, holding great potential for clinical application. Statement of SignificanceThis study engineered multi-responsive cascade catalytic nanoassembly (Au@COF@MnO2) with triple enzymatic functions for amplifying ferroptosis therapy and improving the efficiency of PTT in tumor. The nanoassembly exhibited multi-responsive release and great photothermal conversion performance. Glucose consumption-evoked starvation downregulated the hyperthermia-induced expression of HSPs in tumor cells, thereby improving the efficacy of PTT. Mechanism studies suggested that GSH depletion by Au@COF@MnO2 lead to the inactivation of GPX4, which synergized with Mn2+-mediated ROS generation to bolster the accumulation of LPO, thereby inducing high-efficiency ferroptosis. Moreover, the nanoassembly demonstrated trimodal (PT, PA, and MR) imaging in vivo, enabling the visualization of the tumor treatment with nanoassembly. Such nanoassembly exhibited high tumor inhibition and admirable biosafety in tumor therapy in vivo, holding a great potential for clinical application.

An Acceptor-Donor-Acceptor Structured Nano-Aggregate for NIR-Triggered Interventional Photoimmunotherapy of Cervical Cancer.

Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A-D-A-structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η=67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground-state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2 -), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A-D-A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early-stage and advanced cervical cancer treatment.

Gold Nanoparticles-Modified 2D Self-Assembled Amphiphilic Peptide Nanosheets with High Biocompatibility and Photothermal Therapy Efficiency.

Amphiphilic peptides have garnered significant attention due to their highly designable and self-assembling behaviors. Self-assembled peptides hold excellent potential in various fields such as biosensing, environmental monitoring, and drug delivery, owing to their remarkable biological, physical, and chemical properties. While nanomaterials formed by peptide self-assembly have found widespread use in biomedical applications, the development of 2D peptide nanosheets based on the self-assembly of amphiphilic peptides remains challenging in terms of rational design and morphology modulation. In this study, rationally designed amphiphilic peptide molecules are self-assembled into peptide nanosheets (PNS) under specific conditions to encapsulate gold nanoparticles (AuNPs), resulting in the formation of AuNPs/PNS hybrid materials with high photothermal conversion efficiency. The findings demonstrate that 2D PNS enhances the overall photothermal therapy effect of the nanohybrid materials due to their larger hosting area for AuNPs and higher biocompatibility. The well-designed amphiphilic peptides in this study offer insights into the structural design and functional modulation of self-assembled molecules. In addition, the constructed biomimetic-functional 2D inorganic/organic nanohybrid materials hold potential applications in biomedical engineering.

CoS1.097 nanocrystals as new nanoplatforms for photothermal therapy of arterial inflammation.

Cardiovascular diseases caused by atherosclerosis (AS) seriously damage human health. Nano-photothermal technology has been proven to inhibit the development of vascular inflammation by inhibiting the proliferation of inflammatory macrophages. However, photothermal therapy can inhibit the enrichment of AS macrophages in the early stage, but the inhibitory effect is insufficient in the later stage. Herein, we designed and prepared CoS1.097 nanocrystals by a simple hydrothermal method as new nanoplatforms for efficient photothermal therapy of arterial inflammation. CoS1.097 nanocrystals exhibited the degradability to release the cobalt ions, and can inhibit the proliferation of macrophages both in vitro and in vivo resulting from the slowly released cobalt ions. Moreover, CoS1.097 nanocrystals showed intense absorption in the NIR region, thus showing excellent photothermal performance. When irradiated by an 808 nm laser, the photothermal effect of CoS1.097 nanocrystals can more efficiently kill the macrophages which play an important role in the development of atherosclerosis. As far as we know, this is the first work on CoS1.097 nanocrystals for photothermal therapy of arterial inflammation.

Calcium ascorbate loaded ultrathin ferrous sulfide nanosheets thermo-sensitive hydrogels for near-infrared light activation of synergistic endometriosis therapy

Endometriosis can cause endometrial inflammation and affect women’s reproductive health. However, it’s still challenging to develop efficient endometriosis treatment strategies until now. Herein, a novel near-infrared light (NIR)-activated hydrogel nanostructure (Vc-Ca/UFNs@Gel) with ultrathin ferrous sulfide nanosheets (UFNs) and calcium ascorbate (Vc-Ca) was developed for in situ photothermal/ferroptosis/immune synergistic endometriosis therapy. UFNs with high photothermal conversion efficiency can convert NIR into heat to achieve efficient photothermal therapy (PTT) of endometrial cells, and simultaneously melt the hydrogels to achieve the release of Vc-Ca and UFNs. Vc-Ca can greatly prevent UFNs with ultrathin nanostructure from oxidation and keep their photothermal capacity, as well as directly inhibit the proliferation of endometrial cells. UFNs with dose-dependent internalization decomposed into H2S and Fe2+ ions in endometrial cell, catalyzing the self-oxidation process of Vc-Ca to generate H2O2 and enhancing Fe2+-triggered ferroptosis of endometriosis. Interestingly, ferroptosis and PTT-triggered endometrial cell apoptosis could also induce immunogenic cell death and enhance subsequent immunotherapy. Importantly, our hydrogels can be degradable in vivo with high safety. Overall, our work proposed a novel in situ photothermal/ferroptosis/immune synergistic endometriosis therapy strategy and may have significantly potential clinical application prospects.

An Intramolecular Rotor-Bridged Dimeric Cyanine Photothermal Transducer for Efficient Near-Infrared II Fluorescence Imaging-Guided Mitochondria-Targeted Phototherapy.

Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical properties and high photothermal conversion ability. However, HCy photothermal transducers usually have poor photostability due to degradation induced by the self-generated reactive oxygen species. Herein, a novel mitochondria-targeting dimeric HCy dye, named dimeric oBHCy, is rationally designed, exhibiting strong near-infrared II (NIR-II) fluorescence emission, high photothermal conversion efficiency (PCE), and excellent photostability. The large π-conjugation and drastic intramolecular motion of the diphenol rotor in the dimeric oBHCy enhance the nonradiative energy dissipation and suppress the intersystem crossing process, thereby achieving a high PCE (49.2%) and improved photostability. Impressively, dimeric oBHCy can precisely target mitochondria and induce mitochondrial damage upon NIR light irradiation. Under the guidance of in vivo NIR-II fluorescence imaging, efficient NIR light-activated photothermal therapy of 4T1 breast tumors is accomplished with a tumor inhibitory rate of 96% following a single injection of the dimeric oBHCy. This work offers an innovative strategy for designing cyanine photothermal transducers with integrated NIR-II fluorescence and photothermal properties for efficient cancer theranostics.

Phthalocyanine J-aggregate nanoparticles with enormous-redshifted and intense absorption: Potential structure-J-aggregation relationships and application in tumor-associated macrophages-targeted phototheranostics

Phthalocyanines (Pcs) are considered promising in cancer phototherapy. However, their maximum absorption wavelengths are only around 700 nm, which cannot allow deep tissue penetration and leads to poor therapeutic efficacy. To expand their clinical application, significantly shifting their absorption to longer wavelengths is urgently required. Dye J-aggregates exhibit a redshifted absorption relative to its monomer. However, Pc J-aggregates with enormous-redshifted and intense absorption is rarely reported, and little is known about the relationships between Pc structure and J-aggregation. Herein, such Pc J-aggregates are ingeniously conceived. With a yeast β-D-glucan-ursodeoxycholic acid conjugate as a potential tumor-associated macrophages (TAMs)-targeting carrier and 1-(4-carboxyethylphenoxy) zinc (II) phthalocyanine (Pc1) as a model, Pc1 J-aggregate nanoparticle (NanoPc1) is obtained via ultrasonication-aided emulsification-solvent evaporation technique. NanoPc1 displays strong absorption at 830 nm, with a 156 nm redshift. Further investigation on another twenty-four Pcs demonstrates that unsubstituted zinc (II) or magnesium (II) Pc and hydrophobic mono-substituted zinc (II) or magnesium (II) Pcs with mono-substituted phenoxy or phenylthio or naphthoxy as a substituent can readily form desired Pc J-aggregates with significant redshifts (140–165 nm). The other Pcs fail to form expected J-aggregates probably due to absence of central metals, steric hindrance on central metals (atoms), forming axial coordination on central metals, disorder tendency during self-assembly or hydrophilicity. The theoretical calculation indicates that Pc1 in its J-aggregates exhibits a spiral-like arrangement, and the reduction in the energy gap between HOMO and LUMO and variation of intermolecular π-π interaction caused by J-aggregate formation are responsible for the huge redshift. Additionally, using NanoPc1 as an exemplar, such Pc J-aggregate nanoparticles are substantiated to afford TAMs-targeted and efficient tri-modal imaging and photothermal therapy in a H22 mouse model.

NIR activated upconversion based nanocatalysts for CT/PA imaging-guided triple synergistic PTT/PDT/CDT cancer treatment

Photodynamic therapy (PDT), as a non-invasive treatment, is expected to be widely used in clinical cancer treatment. In this paper, a near-infrared (NIR) light responsive Lu2O3:Yb/Er/Li-Ce6@MIL-101/GOx-PDA (LCMGP) nanodiagnostic platform was prepared for CT/PA imaging-guided multimodality synergistic therapy. Under 808 nm laser irradiation, Lu2O3:Yb/Er/Li-Ce6 (LC) NPs in the nano-diagnostic platform are activated and sensitized by NIR light, resulting in the generation of more single-linear oxygen (1O2) for efficient PDT. Glucose oxidase (GOx) and MIL-101 (Fe) nanozymes can utilize their excellent enzyme cascade catalytic properties and peroxidase-like catalytic properties to undergo glycolysis reactions and catalyze the decomposition of endogenous hydrogen peroxide (H2O2), producing a large amount of hydroxyl radicals (•OH), achieving efficient chemodynamic therapy (CDT). The functionalized modification of polydopamine (PDA) endows the LCMGP nanoparticles with higher photothermal conversion efficiency, which can prompt high local temperature at the tumor site under the irradiation of NIR light to achieve efficient photothermal therapy (PTT). In addition, hyperthermia accelerates the catalytic efficiency of the nanozymatic cascade of LCMGP nanoparticles to enhance ROS production while increasing cellular uptake, resulting in PTT-induced PDT/CDT synergistic effect (96%). Based on the excellent photothermal conversion effect of PDA and the high X-ray attenuation effect of Lu/Fe, the LCMGP nanotherapeutic system demonstrates good CT/PA imaging function, providing new insights and ideas for imaging-mediated multimodal synergistic therapy.

A cascade nanosystem with “Triple-Linkage” effect for enhanced photothermal and activatable metal ion therapy for hepatocellular carcinoma

Due to the limitations of single-model tumor therapeutic strategies, multimodal combination therapy have become a more favorable option to enhance efficacy by compensating for its deficiencies. However, in nanomaterial-based multimodal therapeutics for tumors, exploiting synergistic interactions and cascade relationships of materials to achieve more effective treatments is still a great challenge. Based on this, we constructed a nanoplatform with a “triple-linkage” effect by cleverly integrating polydopamine (PDA), silver nanoparticles (AgNPs), and glucose oxidase (GOx) to realize enhanced photothermal therapy (PTT) and activatable metal ion therapy (MIT) for hepatocellular carcinoma (HCC) treatment. First, the non-radiative conversion of PDA under light conditions was enhanced by AgNPs, which directly enhanced the photothermal conversion efficiency of PDA. In addition, GOx reduced the synthesis of cellular heat shock proteins by interfering with cellular energy metabolism, thereby enhancing cellular sensitivity to PTT. On the other hand, H2O2, a by-product of GOx-catalyzed glucose, could be used as an activation source to activate non-toxic AgNPs to release cytotoxic Ag+, achieving activatable Ag+-mediated MIT. In conclusion, this nanosystem achieved efficient PTT and MIT for HCC by exploiting the cascade effect among PDA, AgNPs, and GOx, providing a novel idea for the design of multimodal tumor therapeutic systems with cascade regulation.Graphical abstract

Optical Microneedle-Lens Array for Selective Photothermolysis.

Photothermolysis is the process that converts radiation energy into thermal energy, which results in the destruction of surrounding tissues or cells through thermal diffusion. Laser therapy that is based on photothermolysis has been a widely used treatment for various skin diseases such as skin cancers and port-wine stains. It offers several benefits such as non-invasiveness and selective treatment. However, the use of light, e.g., laser, for safe and effective photothermolysis becomes challenging due to the limited penetration of light into skin tissue as well as the presence of melanin, which absorbs this light. To solve the current issues, we propose an optical microneedle-lens array (OMLA) coated with gold in this work to directly deliver light to targeted skin layers without being absorbed by surrounding tissues as well as melanin, which results in the improvement of the efficiency of photothermal therapy. We developed a novel fabrication method, frame-guided micromolding, to prepare the OMLA by assembling two negative molds with simultaneous alignment. In addition, evaluations of the optical and heat transfer characteristics of the OMLA were performed. We expect our developed OMLA to play a crucial role in realizing more effective laser therapy by allowing the precise delivery of photons to the target area.

H2O2 self-supplying Ce6@ZIF-8/PDA/CuO2/HA (CZPCH) nanoplatform for enhanced reactive oxygen species (ROS)-mediated tumor therapy

Tumor hypoxia, limited H2O2 levels, and abundant glutathione (GSH) in the tumor microenvironment (TME) pose challenges for high-efficiency reactive oxygen species (ROS)-mediated therapies. To address these limitations, an intelligent ROS-mediated nanoplatform, Ce6@ZIF-8/PDA/CuO2/HA (CZPCH), with photodynamic activity, self-supplied H2O2, Fenton-like reaction, GSH-depletion and photothermal activity was designed for efficient tumor treatment. In the acidic TME, CuO2 in CZPCH deposits into Cu2+ and H2O2, consuming GSH and triggering Fenton-like reactions to generate hydroxyl radical (•OH), enabling efficient chemodynamic therapy (CDT). Moreover, the presence of Ce6 and PDA enables CZPCH to exhibit excellent singlet oxygen (1O2) and temperature increase performance 660 nm and 808 nm laser irradiation, respectively, resulting in efficient photodynamic therapy (PDT) and photothermal therapy (PTT) efficacy. Interestingly, the temperature increase from PTT significantly enhances •OH and 1O2 generation, achieving high-efficiency ROS-based therapeutic efficacy. This synergistic CDT/PDT/PTT treatment demonstrates excellent anti-tumor efficacy and illuminates novel ROS-based therapeutic strategy design.

Boron Cluster Renders Organic Radicals Water-Stable for Photothermal Anti-Infections.

Water-stable organic radicals are promising photothermal conversion candidates for photothermal therapy (PTT). However, organic radicals are usually unstable in biological environments, which greatly hinders their wide application. Here, we have developed a chaotropic effect-based and photoinduced water-stable supramolecular radical (MB12-2) for efficient antibacterial PTT. The supramolecular radical precursor MB12-1 was constructed by the chaotropic effect between closo-dodecaborate cluster (B12H122-) and N,N'-dimethylated dipyridinium thiazolo [5,4-d] thiazole (MPT2+). Subsequently, with triethanolamine (TEOA) serving as an electron donor, MB12-1 could transform to its radical form MB12-2 through photoinduced electron transfer (PET) under 435-nm laser irradiation. The N2 adsorption-desorption analysis confirmed that MB12-2 was tightly packed through the introduction of B12H122-, which effectively enhanced its stability via a spatial site-blocked effect. Moreover, the half-life of MB12-2 in water was calculated through ultraviolet-visible light (UV-vis) absorption spectra results for periods as long as 20 days. In addition, in the skin infection model, MB12-2, as a wound dressing, showed remarkable photothermal antibacterial activity (>97%) under 660-nm laser irradiation and promoted wound healing. This study presents a simple method for designing long-term water-stable supramolecular radicals, offering a novel avenue for noncontact treatments for bacterial infections.

Self-enhanced regulation of stable organic radicals with polypeptide nanoparticles for mild second near-infrared phototheranostics

Stable organic radicals have emerged as a promising option to enhance fluorescence quantum yield (QY), gaining traction in medical treatment due to their unique electronic transitions from the ground state (D0) to the doublet excited state (D1). We synthesized a stable dicyanomethyl radical with a NIR-II fluorescence QY of 0.86 %, surpassing many NIR-II organic dyes. Subsequently, amphiphilic polymer-encapsulated nanoparticles (NPs) containing the radical were created, achieving a NIR-II fluorescence QY of 0.32 %, facilitating high-contrast bio-imaging. These CNPPs exhibit self-enhanced photothermal properties, elevating photothermal conversion efficiency (PCE) from 43.5 % to 57.5 % under 915 nm laser irradiation. This advancement enables more efficient photothermal therapy (PTT) with lower dye concentrations and reduced laser power, enhancing both feasibility and safety. Through regular fractionated mild photothermal therapy, we observed the release of damage-associated molecular patterns (DAMPs) and an increase in cytokine expression, culminating in combined mild phototherapy (m-PTT)-mediated immunogenic cell death (ICD). Consequently, we developed an immunostimulatory tumor vaccine, showcasing a novel approach for refining photothermal agents (PTA) and optimizing the PTT process.

An innovative stepwise activated coupling reaction for fabricating functional fluorescence probes with potential photosensitive applications

Coupling bright organic emitters with biocomponents such as proteins and amino acids to fabricate biocompatible optical functional materials is receiving increasing attention. Previous reports of an efficient, typical reaction between maleic anhydride (MAH) and amino groups indicated that MAH derivatives have great potential for bioconjugation applications. However, the obstacle of complex synthesis methods and weak fluorescence to this kind of derivative structures based on MAH, have greatly limited their applications. Herein, an innovative strategy was developed based on stepwise activated coupling via a multi-step process. First, a series of donor–acceptor emitting frameworks was constructed by introducing different commercially available electron donors into the electron-withdrawing squaric acid core. Then, these frameworks were further activated to obtain different 3,4-diaryl MAH precursors for bioconjugation, which contributed to a novel light-triggered ring-enlargement effect. Importantly, the MAH precursors triggered catalyst-free coupling reactions at ambient temperature with organic small molecules and biological macromolecules containing primary amine groups. Different fluorescent precursors and abundant biological components were effectively combined, and a water-soluble, biocompatible photosensitizer with efficient photodynamic and photothermal therapy effects was obtained. This strategy is expected to have great potential for biological imaging and theragnostic applications.

One‐Hour Ambient‐Pressure‐Dried, Scalable, Stretchable MXene/Polyurea Aerogel Enables Synergistic Defense Against High‐Frequency Mechanical Shock and Electromagnetic Waves

AbstractThe rapid, energy‐efficient, scalable preparation of high‐strength, flexible, multifunctional nanostructured aerogels is highly desired yet challenging. Here, an ambient‐pressure‐dried (APD) strategy is developed involving self‐foaming, dip‐coating, and graphene oxide (GO)‐assisted multiple cross‐linking treatments for the prompt, large‐area preparation of polyurea/transition metal carbides/nitrides (MXenes) aerogels. The APD MXene‐based aerogels showcase low density, remarkable mechanical strength, and ultraflexiblity involving stretchability, good conductivity, hydrophobicity, and high resistance to various solvents. Synergies of robust, elastic cell walls and porous structure contribute to high‐efficiency absorption of high‐frequency, high‐speed mechanical shock waves for the aerogels, significantly transcendinging the biomasses, plastics, elastomers, ceramics, and metals. In addition to the excellent microwave shielding performance of over 40 dB in ultrabroadband frequencies of 4–40 GHz, the oxidation stability is elevated for APD MXene aerogels, consequently yielding applicability in harsh conditions. Furthermore, the superior light absorption capability of aerogels leads to the efficient photothermal conversion, therapy, antibacterial, desalination, water purification, deicing, and thick oil absorption. This work provides a facile, time‐ and energy‐efficient, scalable APD methodology for manufacturing large‐area, high‐strength, ultraflexible, multifunctional MXene‐based aerogels, enlighting a novel synergistic defense against mechanical shock and electromagnetic waves, and promoting them as a prospective candidate in aerospace, device protection, and next‐generation electronics.

DNA-templated synthesis of surface vacancy-rich bifunctional copper sulfide promotes phototherapy via gene regulation

The current photodynamic performance of CuS nanoparticles (CuS NPs) alone is still greatly challenged by the low quantum yield of reactive oxygen species (ROS). At the same time, the efficiency of photothermal therapy (PTT) and photodynamic therapy (PDT) is reduced due to the self-protective ability of tumor cells when attacked by hyperthermia and ROS. To address this issue, we synthesized DCuxS NPs using customized DNA templates through a surface vacancy-rich engineering strategy. In addition to their inherent photothermal properties, the surface vacancy-rich of DCuxS NPs effectively hinders electron-hole pair complexation, thereby enhancing their photodynamic properties. Furthermore, the tumor-targeting NC3S aptamer and the i-motif DNA/Nrf2 siRNA chimera were attached to both ends of the DNA template. The final NDCuxS@siRNA NPs were highly enriched in tumor cells, while the i-motif undergoes a conformational change to release Nrf2 siRNA upon acidic stimulation for Nrf2 pathway blocking to decrease tumor cell protection effect against ROS and high temperature, creating a favorable tumor microenvironment for enhanced PTT and PDT effects. In this study, we explored the potential of DNA templates for engineering nanomaterials, enhanced the photodynamic properties of DCuxS NPs through a surface vacancy-rich strategy, and exploited the versatility of DNA templates to combine phototherapy with gene regulation, providing a promising approach for clinical tumor treatment.

Near-Infrared Light-Driving Organic Photothermal Agents with an 88.9% Photothermal Conversion Efficiency for Image-Guided Synergistic Phototherapy.

Photothermal agents (PTAs) with desirable near-infrared (NIR) absorption and excellent photothermal conversion efficiency (PCE) are ideal candidates for cancer treatment. However, numerous PTAs still require high-intensity and long-duration laser irradiation to completely ablate the tumor during the photothermal therapy (PTT) process, resulting in light damage to healthy skin and tissue as well as limiting their biomedical applications. Integrating intense NIR absorption and high PCE into a single small-molecule PTA is an important prerequisite for realizing efficient PTT, but is a serious challenge. Herein, a series of donor-acceptor type PTAs (CC1 to NC4) are designed through a molecular engineering strategy. Theoretical calculations and experimental results show that the NIR absorption and photothermal effect from CC1 to NC4 are significantly enhanced as expected. Notably, NC4 nanoparticles exhibit intense NIR absorption, superhigh PCE of up to 88.9% for PTT, photoacoustic imaging and photothermal imaging, and effective reactive oxygen species generation for photodynamic therapy (PDT). The superior PTT/PDT synergistic phototherapeutic efficacy is well demonstrated by the complete elimination of tumor in vivo upon one-time, low-intensity, and short-duration laser irradiation (808nm, 330mW cm-2, and 3min). This work provides a valuable guideline for rational design of PTAs for cancer phototherapy.

Acceptor-donor-acceptor type organic photothermal agents with enhanced NIR absorption and photothermal conversion effect for cancer photothermal therapy

Numerous photothermal agents (PTAs) require high-intensity and long-duration laser excitation for photothermal therapy (PTT), resulting in light damage to healthy skin and tissue as well as limiting their biomedical applications. Integrating desirable near-infrared (NIR) absorption and high photothermal conversion efficiency (PCE) into a single small-molecule PTA is an important prerequisite for realizing efficient PTT, but is a serious challenge. Herein, through molecular engineering strategy, an acceptor-donor-acceptor (A-D-A) type PTA (ADA3) was readily developed for 808 nm laser-driving photothermal imaging and PTT of tumor. Theoretical calculations and experiment results show molecular engineering strategy is significant in regulating the structure and energy gap of PTAs, so as to effectively induce a narrow band gap for NIR absorption and further optimize photothermal properties. ADA3 possesses molar extinction coefficient of 3.1 × 104 M−1 cm−1 at 808 nm, followed being assembled into nanoparticles, ADA3-NPs show high PCE of 80.3%. In vivo experiments indicate that ADA3-NPs have excellent antitumor capability under one-time, low-intensity and short-duration (808 nm, 330 mW/cm2, 3 min) laser irradiation. Therefore, this work definitely exemplifies the enormous potential of molecular engineering strategy and provides an effective method for developing small-molecule PTAs.

Applications of Cu2+-Loaded Silica Nanoparticles to Photothermal Therapy and Tumor-Specific Fluorescence Imaging.

Copper-based nanomaterials have been employed as therapeutic agents for cancer therapy and diagnosis. Nevertheless, persistent challenges, such as cellular toxicity, non-uniform sizes, and low photothermal efficiency, often constrain their applications. In this study, we present Cu2+-loaded silica nanoparticles fabricated through the chelation of Cu2+ ions by silanol groups. The integration of Cu2+ ions into uniformly sized silica nanoparticles imparts a photothermal therapy effect. Additionally, the amine functionalization of the silica coating facilitates the chemical conjugation of tumor-specific fluorescence probes. These probes are strategically designed to remain in an 'off' state through the Förster resonance energy transfer mechanism until exposed to cysteine enzymes in cancer cells, inducing the recovery of their fluorescence. Consequently, our Cu2+-loaded silica nanoparticles demonstrate an efficient photothermal therapy effect and selectively enable cancer imaging.

Platinum Nanoparticles-Enhanced Ferritin-Mn2+ Interaction for Magnetic Resonance Contrast Enhancement and Efficient Tumor Photothermal Therapy.

Nanoplatforms with high Mn2+ coordination can display efficient T1 magnetic resonance imaging (MRI) contrast enhancement. Herein, an earth gravity-like method for enhanced interaction between Ferritin (Fn) and Mn2+ by the growth of platinum nanoparticles (PNs) in Fn's cage structure via a biomineralization method is first proposed. Fn has good biocompatibility and can provide a suitable growth site for PNs. PNs with negative charge have certain attraction to Mn2+ with positive charge, improving Fn's loading capacity of Mn2+ by attraction force; and thus, achieving efficient MRI contrast enhancement. In addition, PNs can be applied for efficient photothermal therapy (PTT) under near infrared ray (NIR) irradiation. Systemic delivery of this nanoplatform shows obvious MRI contrast enhancement and tumor progression inhibition after NIR irradiation, as well as no obvious side effects. Therefore, this nanoplatform has the potential to contribute to nanotheranostic for clinical transformation.