Near-infrared Photothermal Therapy Research Articles

Biodegradable ICG-Conjugated Germanium Nanoparticles for In Vivo Near-Infrared Dual-Modality Imaging and Photothermal Therapy.

Theranostics, by integrating diagnosis and therapy on a single platform, enables real-time monitoring of tumors during treatment. To improve the accuracy of tumor diagnosis, the fluorescence and photoacoustic imaging modalities can complement each other to achieve high resolution and a deep penetration depth. Despite the superior performance, the biodegradability of theranostic agents plays a critical role in enhancing nanoparticle excretion and reducing chronic toxicity, which is essential for clinical applications. Herein, we synthesize biocompatible and biodegradable indocyanine green (ICG)-conjugated germanium nanoparticles (GeNPs) and investigate their biodistributions in nude mice and 4T1 tumor models after intravenous injections using near-infrared (NIR) dual-modality fluorescence and photoacoustic imaging. The ICG-conjugated GeNPs have strong NIR absorption due to the NIR-absorbing ICG and Ge in combination, emit strong NIR fluorescence due to the multilayered ICG coatings, and exhibit very low in vitro and in vivo toxicity. After tail vein injections, the ICG-conjugated GeNPs mainly accumulate in the liver and spleen as well as the tumor with the help of the enhanced permeability and retention effect. The tumor's fluorescence signal is much stronger than that of the control group injected with pure ICG solution, as the GeNPs can function as biodegradable carriers for efficiently delivering the ICG molecules to the tumor. Lastly, the ICG-conjugated GeNPs accumulated in the tumor can also be utilized for photothermal treatment under NIR laser irradiation, after which the tumor volume almost diminishes after 14 days. The experimental findings in this work demonstrate that the ICG-conjugated GeNPs are promising theranostic agents with exceptional biodegradability for in vivo NIR dual-modality imaging and photothermal therapy.

Supramolecular Porphyrin Photosensitizers Based on Host-Guest Recognition for In Situ Bacteria-Responsive Near-Infrared Photothermal Therapy.

Antibiotic resistance resulting from the overuse of antibiotics sets a high challenge for brutal antimicrobial treatment. Although photothermal therapy (PTT) overcomes the awkward situation of antibiotic resistance, it usually mistakenly kills the beneficial bacteria strains when eliminating pernicious bacteria. Specifically recognizing and damaging the target pathogens is urgently required for PTT-mediated sterilization strategy. Based on the host-guest recognition between cucurbit[10]uril (CB[10]) and porphyrins, two water-soluble supramolecular porphyrins are designed and implement selective bactericidal effect via in situ bacteria-responsive near-infrared (NIR) PTT. With the help of CB[10], the π-π stacking and hydrophobic interactions of porphyrins are efficiently inhibited, thus contributing to a good photostability and a high photothermal conversion efficiency. Attributing to the matching reduction potential between facultative anaerobic Escherichia coli (E. coli) and porphyrins, they are selectively in situ reduced into supramolecular phlorin and supramolecular chlorin by E. coli, successfully achieving a selective sterilization against E. coli. In vivo, the in situ bacteria-responsive NIR PTT systems also promote the quick recovery of E. coli-infected abscesses and trauma on mice without inducing obvious systemic toxicity, providing a new alternative to the current antibiotics and helping relieve the global public health crisis of abusive antibiotics.

D-arginine-functionalized carbon dots with enhanced near-infrared emission and prolonged metabolism time for tumor fluorescent-guided photothermal therapy

Carbon dots (CDs) have garnered significant interest owing to their distinctive optical properties. However, their bioimaging and biomedical applications are limited by pronounced fluorescence (FL) quenching in aqueous media and low tumor accumulation efficacy associated with their ultra-small size. This study proposes a simple surface modification approach using functioning d-arginine on CDs (d-Arg@CDs) to improve their near-infrared (NIR) FL in aqueous solution and maintain their high photothermal conversion properties. Because of the low utilization rate of dextral amino acids in animals, modifying CDs with low molecular weight d-arginine did not increase particle size but extended the metabolism time in blood circulation, thereby leading to enhanced accumulation efficacy at tumor sites in the mice model. The enhanced tumor accumulation of d-Arg@CDs resulted in significantly superior tumor NIR FL imaging and photothermal therapy performance compared with pure CDs and l-arginine functionalized CDs. This dextral amino acid modification approach is expected to be an effective tool for enhancing the biomedical applications of CDs.

Cairo pentagon tessellated covalent organic frameworks with mcm topology for near-infrared phototherapy

Despite the prevalent of hexagonal, tetragonal, and triangular pore structures in two-dimensional covalent organic frameworks (2D COFs), the pentagonal pores remain conspicuously absent. We herein present the Cairo pentagonal tessellated COFs, achieved through precisely chosen geometry and metrics of the linkers, resulting in unprecedented mcm topology. In each pentagonal structure, porphyrin units create four uniform sides around 15.5 Å with 90° angles, while tetrabiphenyl unit establish a bottom edge about 11.6 Å with 120° angles, aligning precisely with the criteria of Cairo Pentagon. According to the narrow bandgap and strong near-infrared (NIR) absorbance, as-synthesized COFs exhibit the efficient singlet oxygen (1O2) generation and photothermal conversion, resulting in NIR photothermal combined photodynamic therapy to guide cancer cell apoptosis. Mechanistic studies reveal that the good 1O2 production capability upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. The implementation of pentagonal Cairo tessellations in this work provides a promising strategy for diversifying COFs with new topologies, along with multimodal NIR phototherapy.

The photothermal coupling of TiN@Au core-shell nanorods applied to near-infrared photothermal therapy

Thermal plasmonic nanoparticles offer a novel and significant approach for photothermal therapy in the medical field, which is photothermal therapy of cancer. This study introduces a type of core-shell nanorods with internal coupling of titanium nitride (TiN) and gold (Au) nanomaterials. The photothermal properties of these nanorods in the near infrared (NIR) band were investigated using COMSOL Multiphysics software and the finite element method. Results indicate that TiN@Au and Au@TiN core-shell nanorods exhibit superior photothermal properties in the NIR band compared to pure TiN nanorods of similar volume. Furthermore, core-shell nanorods with polarization angles of 0° and 45° demonstrate enhanced optical absorption properties in the near infrared range. Furthermore, the study on the tunability of localized surface plasmon resonance with variations in core diameter, shell thickness, and combined changes of core diameter and shell thickness for core-shell nanorods of equal volume suggests that TiN@Au core-shell nanorods with a 10 nm Au shell offer increased optical absorption efficiency and photothermal conversion capability. Ultimately, the TiN and Au core-shell nanorods proposed in this research offer valuable insights for the structural design and heat transfer control of nanoparticle heat generators to enhance fluid temperature, as well as provide practical guidance for the preparation of core-shell nanoparticles.

NIR-responsive CN-Pt-GEM hydrogel induces necroptosis and immunotherapeutic responses prevent postoperative recurrence and wound infection in lung carcinoma

BackgroundCancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse.ResultsThe hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection.ConclusionsThese findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.

Ginsenoside Rg3 combined with near-infrared photothermal reversal of multidrug resistance in breast cancer MCF-7/ADR cells.

Adriamycin (ADR) is a frequently employed chemotherapeutic agent for the management of breast cancer. Nevertheless, multidrug resistance (MDR) can impair its therapeutic efficacy in breast cancer. MDR is characterized by increased expression of the P-glycoprotein (P-gp) efflux pump, up-regulation of anti-apoptotic proteins, and downregulation of pro-apoptotic proteins. Consequently, inhibition of ATP-binding cassette (ABC) transporter proteins has been deemed the most efficacious approach to overcome MDR. In this study, we used MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), Western blots, flow cytometry, immunofluorescence, and constructed xenograft tumors to investigate whether ginsenoside Rg3-near-infrared photothermal (Rg3-NIR) combination reversed multidrug resistance in MCF-7/ADR breast cancer. Invivo and invitro experiments, the results showed that Rg3-NIR co-treatment was effective in inducing the apoptosis of MCF-7/ADR breast cancer cells. This was achieved by reversing the expression of drug resistance-associated proteins, while also inhibiting cell proliferation, migration, and epithelial-mesenchymal transition (EMT) processes via attenuation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway transduction. Ginsenoside Rg3 combined with near-infrared photothermal therapy (NIR) effectively reverses multidrug resistance in breast cancer MCF-7/ADR cells, providing a new therapeutic strategy for breast cancer drug resistance.

Chaotropic Effect-Induced Sol-Gel Transition and Radical Stabilization for Bacterially Sensitive Near-Infrared Photothermal Therapy.

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.

Analysis of photothermal coupling of titanium nitride nanorods applied to near-infrared photothermal therapy

Titanium nitride (TiN) serves as an ideal reagent for photothermal therapy due to its cost-effectiveness, stability, and biocompatibility. This study investigates the optical and thermal properties of TiN nanoparticles in the near-infrared (NIR) region. Specifically, we employ the COMSOL Multiphysics software to solve Maxwell's equations using a finite element method, enabling us to investigate the photothermal characteristics of individual TiN nanorods. To ensure accurate photothermal coupling calculations, we utilize the Fourier steady-state heat conduction equation. The results demonstrate that the nanorod photothermal properties exhibit significantly enhanced effects when the incident light is polarized along the long axis of the rod, while the thermal properties of the nanorods are primarily influenced by their optical absorption efficiency. The tunability investigation of the nanorods demonstrates that an increase in aspect ratio (AR) results in a red-shift of the absorption peaks. Concurrently, there is an expansion in the bandwidth corresponding to the absorption peak, accompanied by an augmentation in its peak value. It is evident that at AR = 5, the TiN nanorods exhibit enhanced photothermal properties in the NIR region, resulting in a temperature increase of 43 K in the surrounding medium through efficient heat transfer. Consequently, this accomplishment enables achieving the desired temperature range for effective photothermal therapy. The significance of this study lies in providing a valuable reference and theoretical guidance for exploring the utilization of TiN nanorods in photothermal therapy, with a specific focus on attaining a more precise understanding of temperature elevation and distribution during the treatment process.

Cancer-targeting gold-decorated melanin nanoparticles for in vivo near-infrared photothermal therapy

Melanin-like nanoparticles decorated with gold nanoparticles are presented as cancer-targeting near-infrared (NIR) photothermal agents with excellent photothermal conversion and stability.

A Covalent Organic Framework Derived N-doped Carbon Nanozyme as the All-rounder for Targeted Catalytic Therapy and NIR-II Photothermal Therapy of Cancer.

Nanomaterials with intrinsic enzyme-like activities (nanozymes) have gained significant attention in cancer catalytic therapy; however, developing metal-free nanozymes with multivariant enzyme-like activity as the "all-rounder" for cancer therapy remains challenging. Herein, a covalent organic framework (COF) derived carbon-based nanozyme is rationally devised to achieve synergistic catalytic therapy and second near-infrared (NIR-II) photothermal therapy of cancer. The developed nanozyme possesses multivariant enzyme-like activities, including oxidase (OXD)-like, catalase (CAT)-like, and peroxidase (POD)-like catalytic activities, which enables the nanozyme to produce adequate reactive oxygen species (ROS) for cancer cell killing. Furthermore, the nanozyme showed excellent photothermal converting activity that could kill cancer cells upon NIR-II laser irradiation, owing to the strong NIR-II absorption capacity of carbon-based materials. It is also worth noting that the nanozyme exhibited cytotoxicity specifically in tumor tissue profiting from the discrepant H2O2 level between tumor and normal tissue and the spatiotemporal controllability of laser irradiation. This work may inspire further development of intelligent nanozymes in biological applications across broad therapeutic and biomedical fields.

Biogenic Copper Selenide Nanoparticles for Near-Infrared Photothermal Therapy Application.

Near-infrared (NIR) photothermal therapy (PTT) is attractive for cancer treatment but is currently restricted by limited availability and insufficient NIR-II photoactivity of photothermal agents, for which artificial nanomaterials are usually used. Here, we report the first use of biogenic nanomaterials for PTT application. A fine-controlled extracellular biosynthesis of copper selenide nanoparticles (bio-Cu2-xSe) by Shewanella oneidensis MR-1 was realized. The resulting bio-Cu2-xSe, with fine sizes (∼35.5 nm) and high product purity, exhibited 76.9% photothermal conversion efficiency under 1064 nm laser irradiation, outperforming almost all the existing counterparts. The protein capping also imparted good biocompatibility to bio-Cu2-xSe to favor a safe PTT application. The in vivo PTT with injected bio-Cu2-xSe in mice (without extraction nor further modification) showed 87% tumor ablation without impairing the normal organisms. Our work not only opens a green route to synthesize the NIR-II photothermal nanomaterial but may also lay a basis for the development of bacteria-nanomaterial hybrid therapy technologies.

Insight into the photothermal therapeutic impacts of silica-coated iron oxide nanocomposites

Recently, near-infrared photothermal therapy combined with targeted nano-sensitizer has been used for cancer eradication as it protects the surrounding tissues. Although iron oxide nanoparticles (INPs) are efficient photo-heat conversion agents, they tend to agglomerate, restricting their utility in medical applications. We prepared silica-coated INPs (SCINPs) to overcome this obstacle. The physical properties of INPs and SCINPs were evaluated using transmission electron microscope (TEM), dynamic light scattering (DLS), vibrating sample magnetometer (VSM), atomic force microscope (AFM) and X-RAY diffraction (XRD). The polydispersity index (PDI) value was 0.21 and 0.44 for INPs and SCINPs, respectively. Zeta potential measurements showed that the prepared nanoparticles had negative net surface charges with average values of −28 ± 4.21 and −48 ± 5 mv for INPs and SCINPs, respectively. This is a pioneered study that evaluate the photothermal therapeutic effect of silica coated iron oxide nanoparticles. In addition to evaluate their photothermal therapeutic effect, as nano photothermal agents, using comet assay and oxidative stress parameters. Also, their photothermal therapeutic effect were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Photothermal assessment indicated that SCINPs could improve the photothermal therapy (PTT) because of their reproducible hyper-thermic and hypo-thermic effects with repeated treatment. Compared to INPs, SCINPs significantly improved the photothermal therapeutic behavior in treated cells by around 1.88 folds. SCINPs were more effective photothermal therapeutic agents and had considerable potential as novel therapeutic agents.

Intramolecular charge transfer versus intersystem crossing: The way toward super-high photothermal efficiency by thionation

Development of organic molecules with high photothermal conversion efficiency (PCE) in the near-infrared (NIR) window is a vital yet challenging topic in the field of photothermal therapy. A series of thionated perylenediimides (PDI-4CHA-S) derivatives have been synthesized by replacing carboxylic oxygens in imides with sulfur atoms, providing chances to unravel the effect of thionation on the photophysical properties toward photothermal agents (PTAs) with high PCE. In the presence of the electron-donating substituents at the bay-position, sulfur atoms participate the intramolecular charge transfer (ICT), which induces remarkable redshift in the absorption maximum. Meanwhile, the ICT together with the heavy atoms effect of sulfur atoms promotes the intersystem crossing (ISC), resulting in the generation of the active oxygen species (ROS) upon photoexcitation. Interestingly, the quantum yield of ROS decrease with increasing the number of S-substitutes, which is the resultant of the attenuated ICT in the case of multiple S-substitution. Overall, the promotion in ISC due to thionation is negligible compared to the quenching of the radiation transition and enhancement of the absorption coefficient caused by ICT, hence the energy of the excited PDI-4CHA-S molecules is depleted mainly in the form of heat, leading to the ultrahigh PCE of 88.0% under 808 nm laser irradiation. In particular, the trithionated PDI-4CHA-3S performs surprisingly high PCE in the second near-infrared (NIR-II) window (1064 nm). The superior photothermal effect and excellent photostability of the thionated PDI derivative provide them promising photothermal agents for NIR photothermal therapy.

Afterglow/Photothermal Bifunctional Polymeric Nanoparticles for Precise Postbreast-Conserving Surgery Adjuvant Therapy and Early Recurrence Theranostic.

Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.

Bimetallic Hyaluronate-Modified Au@Pt Nanoparticles for Noninvasive Photoacoustic Imaging and Photothermal Therapy of Skin Cancer.

Although spherical gold (Au) nanoparticles have remarkable photothermal conversion efficiency and photostability, their weak absorption in the near-infrared (NIR) region and poor penetration into deep tissues have limited further applications to NIR light-mediated photoacoustic (PA) imaging and noninvasive photothermal cancer therapy. Here, we developed bimetallic hyaluronate-modified Au-platinum (HA-Au@Pt) nanoparticles for noninvasive cancer theranostics by NIR light-mediated PA imaging and photothermal therapy (PTT). The growth of Pt nanodots on the surface of spherical Au nanoparticles enhanced the absorbance in the NIR region and broadened the absorption bandwidth of HA-Au@Pt nanoparticles by the surface plasmon resonance (SPR) coupling effect. In addition, HA facilitated the transdermal delivery of HA-Au@Pt nanoparticles through the skin barrier and enabled clear tumor-targeted PA imaging. Compared to conventional PTT via injection, HA-Au@Pt nanoparticles were noninvasively delivered into deep tumor tissues and completely ablated the targeted tumor tissues by NIR light irradiation. Taken together, we could confirm the feasibility of HA-Au@Pt nanoparticles as a NIR light-mediated biophotonic agent for noninvasive skin cancer theranostics.

Dopamine multivalent-modified polyaspartic acid for MRI-guided near-infrared photothermal therapy.

Nanophotothermal agents that provide efficient and precise treatment at tumor sites are attracting increasing attention in biomedicine. In particular, the method combination of nanophotothermal agents and magnetic resonance imaging (MRI) shows great promise for biomedical therapeutic applications. Herein, a simple nanophotothermal agent with dopamine multivalent-modified polyaspartic acid chelated superparamagnetic iron oxide (SPIO) and ferric ion (SPIO@PAsp-DAFe/PEG) was developed for MRI-guided near-infrared photothermal therapy (PTT). SPIO@PAsp-DAFe/PEG was random SPIO nanocluster with good water solubility, had a diameter of 57.8 ± 7.8 nm in dynamic light scattering, negatively charged surface (zeta potential = -11 mV), exhibited good stability and outstanding photothermal conversion efficiency (35.4%) and produced superior magnetic resonance enhanced imaging. In the experiment with tumor-bearing mice, the MRI not only monitored the accumulation of SPIO@PAsp-DAFe/PEG nanocomposites enhanced by near-infrared irradiation after intravenous administration but also determined the appropriate time window for PTT. With the use of MRI-guided near-infrared therapy, the SPIO@PAsp-DAFe/PEG nanocomposites provided excellent therapeutic effects, confirming their great potential as effective MRI/PTT therapeutic agents.

Aqueous green synthesis of organic/inorganic nanohybrids with an unprecedented synergistic mechanism for enhanced near-infrared photothermal performance.

Silver sulfide (Ag2S) nanoparticles (NPs) represent one of the most popular inorganic reagents for near-infrared (NIR) photothermal therapy (PTT). However, the extensive biomedical applications of Ag2S NPs are greatly compromised by the hydrophobicity of the NPs prepared in organic solvents, their low photothermal conversion efficiency, certain surface modification-induced damage to their intrinsic properties and short circulation time. To develop a facile yet efficient green approach to overcome these shortcomings for improved properties and performance of Ag2S NPs, we report herein the construction of Ag2S@polydopamine (PDA) nanohybrids via a "one-pot" organic-inorganic hybridization strategy, which produces uniform Ag2S@PDA nanohybrids with well-modulated sizes in the range of 100-300 nm via the self-polymerization of dopamine (DA) and subsequent synergistic assembly of PDA with Ag2S NPs in a three-phase mixed medium containing water, ethanol and trimethylbenzene (TMB). Integration of dual photothermal moieties, i.e., Ag2S and PDA at a molecular level, endows Ag2S@PDA nanohybrids with synergistically enhanced NIR photothermal properties that are much better than those of either PDA or Ag2S NPs due to calculated combination indexes (CIs) of 0.3-0.7 between Ag2S NPs and PDA based on a modified Chou-Talalay method. Therefore, this study not only developed a facile "one-pot" green approach toward producing uniform Ag2S@PDA nanohybrids with well-modulated dimensions, but also revealed an unprecedented synergistic mechanism for organic/inorganic nanohybrids that is based on dual photothermal moieties providing enhanced near-infrared photothermal performance.

Flower-like Cu9S8 nanocatalysts with highly active sites for synergistic NIR-II photothermal therapy and chemodynamic therapy.

Chemodynamic therapy (CDT) is a promising reactive oxygen species-based therapeutic strategy for tumor therapy. However, the poor reaction kinetics of CDT agents severely restricts its further application. Herein, protamine stabilized flower-like Cu9S8 (PS@Cu9S8) nanocatalysts are fabricated via a one-pot biomineralization strategy for synergistic second near-infrared (NIR-II) photothermal therapy (PTT) and CDT of tumor. The PS@Cu9S8 nanocatalysts possess a high surface area (40.10 m2 g-1), which is higher than those of the previously reported solid and hollow copper sulfide nanoparticles. The high surface area of PS@Cu9S8 nanocatalysts increases the number of active sites during the Fenton-like reaction, thereby accelerating the efficiency of CDT. Meanwhile, the PS@Cu9S8 nanocatalysts show a high extinction coefficient (21.41 L g-1 cm-1) and photothermal conversion efficiency (42.34%), which results in an outstanding PTT efficiency and facilitate ˙OH generation for CDT. Furthermore, RNA-sequencing unveils the whole-genome expression change of 4T1 cells after PS@Cu9S8 nanocatalyst treatment, revealing the apparent changes in ROS, cell cycle, and apoptosis-related pathways. In vivo experiments proved the good therapeutic efficiency and negligible systematic toxicity of PS@Cu9S8 nanocatalysts. This work not only develops a superior multifunctional nanocatalyst for synergistic PTT and CDT of tumor, but also provides a facile approach to construct high-performance agents for cancer therapy.

A carbon dot-doped Cu-MOF-based smart nanoplatform for enhanced immune checkpoint blockade therapy and synergistic multimodal cancer therapy.

Immune checkpoint blockade (ICB) is a kind of promising anti-tumor immunotherapy that can block the negative immune regulatory pathways using a particular antibody. Weak immunogenicity in most patients is a key obstacle to ICB therapy. Photodynamic therapy (PDT) is a non-invasive treatment that can enhance the immunogenicity of the host and realize systemic anti-tumor immunotherapy; yet tumor microenvironment hypoxia and glutathione overexpression severely restrict the PDT effect. To overcome the above issues, we design a combination therapy based on PDT and ICB. We prepared red carbon dot (RCD)-doped Cu-metal-organic framework nanoparticles (Cu-MOF@RCD) as smart nano-reactors because their tumor microenvironment and near-infrared light responsive property can decompose tumor endogenous H2O2 through Fenton-like reactions. Cu-MOF@RCD also shows clear near-infrared photothermal therapy (PTT) effect and has an ability to deplete glutathione (DG), which together enhances decomposition of cellular H2O2 and amplifies reactive oxygen species (ROS) levels in cells, thus leading to enhanced PDT and chemodynamic therapy (CDT) effect. Moreover, programmed cell death-ligand 1 antibody (anti-PD-L1) is used together to enable combination therapy, as Cu-MOF@RCD can significantly enhance host immunogenicity. In summary, the combination of Cu-MOF@RCD with anti-PD-L1 antibody exerts a synergistic PDT/PTT/CDT/DG/ICB therapy and can be used to eradicate the primary tumors and inhibit the growth of untreated distant tumors and tumor metastasis.