Antiferromagnetic Pyrite as the Tumor Microenvironment‐Mediated Nanoplatform for Self‐Enhanced Tumor Imaging and Therapy

Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH‐sensitive imaging, acidity‐sensitive starving therapy, and hydrogen peroxide‐activated chemotherapy, etc. Herein, a novel TME‐mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self‐enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i.e., CDT). The increase of the valence state of surface Fe significantly promotes the performance of MRI accompanied by CDT. Furthermore, the localized heat by photothermal treatment can accelerate the intratumoral Fenton process, enabling a synergetic PTT/CDT. To our best knowledge, this is the first study to use the TME‐response valence‐variable strategy based on pyrite for developing a synergetic nanotheranostic, which will open up a new dimension for the design of other TME‐based anticancer strategies.     

Photosensitizer‐Conjugated Albumin−Polypyrrole Nanoparticles for Imaging‐Guided In Vivo Photodynamic/Photothermal Therapy

Conjugated polymers with strong absorbance in the near‐infrared (NIR) region have been widely explored as photothermal therapy agents due to their excellent photostability and high photothermal conversion efficiency. Herein, polypyrrole (PPy) nanoparticles are fabricated by using bovine serum albumin (BSA) as the stabilizing agent, which if preconjugated with photosensitizer chlorin e6 (Ce6) could offer additional functionalities in both imaging and therapy. The obtained PPy@BSA‐Ce6 nanoparticles exhibit little dark toxicity to cells, and are able to trigger both photodynamic therapy (PDT) and photothermal therapy (PTT). As a fluorescent molecule that in the meantime could form chelate complex with Gd³⁺, Ce6 in PPy@BSA‐Ce6 nanoparticles after being labeled with Gd³⁺ enables dual‐modal fluorescence and magnetic resonance (MR) imaging, which illustrate strong tumor uptake of those nanoparticles after intravenous injection into tumor‐bearing mice. In vivo combined PDT and PTT treatment is then carried out after systemic administration of PPy@BSA‐Ce6, achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone. Hence, a rather simple one‐step approach to fabricate multifunctional nanoparticles based on conjugated polymers, which appear to be promising in cancer imaging and combination therapy, is presented.     

Artificial Engineered Natural Killer Cells Combined with Antiheat Endurance as a Powerful Strategy for Enhancing Photothermal‐Immunotherapy Efficiency of Solid Tumors

Although photothermal therapy (PTT) is preclinically applied in solid tumor treatment, incomplete tumor removal of PTT and heat endurance of tumor cells induces significant tumor relapse after treatment, therefore lowering the therapeutic efficiency of PTT. Herein, a programmable therapeutic strategy that integrates photothermal therapeutic agents (PTAs), DNAzymes, and artificial engineered natural killer (A‐NK) cells for immunotherapy of hepatocellular carcinoma (HCC) is designed. The novel PTAs, termed as Mn‐CONASHs, with 2D structure are synthesized by the coordination of tetrahydroxyanthraquinone and Mn²⁺ ions. By further adsorbing polyetherimide/DNAzymes on the surface, the DNAzymes@Mn‐CONASHs exhibit excellent light‐to‐heat conversion ability, tumor microenvironment enhanced T₁‐MRI guiding ability, and antiheat endurance ability. Furthermore, the artificial engineered NK cells with HCC specific targeting TLS11a‐aptamer decoration are constructed for specifically eliminating any possible residual tumor cells after PTT, to systematically enhance the therapeutic efficacy of PTT and avoid tumor relapse. Taken together, the potential of A‐NK cells combined with antiheat endurance as a powerful strategy for immuno‐enhancing photothermal therapy efficiency of solid tumors is highlighted, and the current strategy might provide promising prospects for cancer therapy.     

A New Co‐P Nanocomposite with Ultrahigh Relaxivity for In Vivo Magnetic Resonance Imaging‐Guided Tumor Eradication by Chemo/Photothermal Synergistic Therapy

Design of new nanoagents that intrinsically have both diagnostic imaging and therapeutic capabilities is highly desirable for personalized medicine. In this work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)‐functionalized Co‐P nanocomposites (Co‐P@PDA) for magnetic resonance imaging (MRI)‐guided combined photothermal therapy and chemotherapy. The ultrahigh relaxivity of 224.61 mm ^?1 s^?1 can enable Co‐P@PDA to be applied as an excellent contrast agent for MRI in vitro and in vivo, providing essential and comprehensive information for tumor clinical diagnosis. Moreover, Co‐P@PDA exhibit excellent photothermal performance owing to the strong near‐infrared (NIR) absorbance of both Co‐P nanocomposite and PDA. Highly effective ablation of tumors is achieved in a murine tumor model because the NIR laser not only induces photothermal effects but also triggers the chemotherapeutic drug on‐demand release, which endows the Co‐P@PDA with high curative effects but little toxicity and few side effects. These findings demonstrate that Co‐P@PDA are promising agents for highly effective and precise antitumor treatment and warrant exploration as novel theranostic nanoagents with good potential for future clinical translation.     

Dual‐Stimuli Responsive Nanotheranostics for Multimodal Imaging Guided Trimodal Synergistic Therapy

Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple “mechanical” combination. Herein, we report a dual‐stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica‐coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5‐fluorouracil (5‐FU), for in vivo multimodal imaging guided synergistic therapy. The 5‐FU loaded ICG‐conjugated silica‐coated gold nanorods (GNR@SiO2‐5‐FU‐ICG) was able to response specifically to the two stimuli of pH change and near‐infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5‐FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2‐5‐FU‐ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two‐photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2‐5‐FU‐ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.     

Transforming Weakness into Strength: Photothermal‐Therapy‐Induced Inflammation Enhanced Cytopharmaceutical Chemotherapy as a Combination Anticancer Treatment

A new synergistic treatment that combines photothermal therapy (PTT) and inflammation‐mediated active targeting (IMAT) chemotherapy based on cytopharmaceuticals is developed. During PTT, the photothermal tumor ablation is accompanied by an inflammatory effect and upregulation of inflammatory factors at the tumor site, which may accelerate tumor regeneration. Moreover, PTT‐induced inflammation can also recruit neutrophils (NEs) to the tumor site. To convert the disadvantages of PTT‐induced inflammation into strengths, NEs are investigated as cytopharmaceuticals for IMAT chemotherapy to further inhibit the tumor recurrence after PTT due to the chemotaxis of NEs to the inflammatory sites. In this study, PEGylated gold nanorods (PEG‐GNRs) are explored as the photothermal agent and paclitaxel‐loaded cytopharmaceuticals of NEs as the IMAT chemotherapeutic agent. PTT is conducted at 72 h postinjection of PEG‐GNRs, followed by cytopharmaceuticals for IMAT chemotherapy. It is demonstrated that the cytopharmaceuticals effectively accumulate in the tumor sites after PTT, which leads to a significant enhancement of antitumor efficacy and a reduction in systemic toxicity. These studies suggest that PTT‐induced inflammation further enhances the chemotherapy of cytopharmaceuticals, and the combination of PTT and IMAT chemotherapy may be a promising synergistic strategy for targeted cancer therapy.     

Manganese Dioxide Coated WS2@Fe3O4/sSiO2 Nanocomposites for pH‐Responsive MR Imaging and Oxygen‐Elevated Synergetic Therapy

Recently, the development of multifunctional theranostic nanoplatforms to realize tumor‐specific imaging and enhanced cancer therapy via responding or modulating the tumor microenvironment (TME) has attracted tremendous interests in the field of nanomedicine. Herein, tungsten disulfide (WS₂) nanoflakes with their surface adsorbed with iron oxide nanoparticles (IONPs) via self‐assembly are coated with silica and then subsequently with manganese dioxide (MnO₂), on to which polyethylene glycol (PEG) is attached. The obtained WS₂‐IO/S@MO‐PEG appears to be highly sensitive to pH, enabling tumor pH‐responsive magnetic resonance imaging with IONPs as the pH‐inert T2 contrast probe and MnO₂ as the pH‐sensitive T1 contrast probe. Meanwhile, synergistic combination tumor therapy is realized with such WS₂‐IO/S@MO‐PEG, by utilizing the strong near‐infrared light and X‐ray absorbance of WS₂ for photothermal therapy (PTT) and enhanced cancer radiotherapy (RT), respectively, as well as the ability of MnO₂ to decompose tumor endogenous H₂O₂ and relieve tumor hypoxia to further overcome hypoxia‐associated radiotherapy resistance. The combination of PTT and RT with WS₂‐IO/S@MO‐PEG results in a remarkable synergistic effect to destruct tumors. This work highlights the promise of developing multifunction nanocomposites for TME‐specific imaging and TME modulation, aiming at precision cancer synergistic treatment.     

Six Birds with One Stone: Versatile Nanoporphyrin for Single-Laser-Triggered Synergistic Phototheranostics and Robust Immune Activation

Simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT) can reduce the risks of drug leakage, body burden, and preparation complexity in traditional combination PDT/PTT. Here, a versatile nanoporphyrin (Pp18-lipos) self-assembled from lipid–purpurin 18 conjugates (Pp18-lipids) and pure lipids is presented. The as-prepared Pp18-lipos with 2 mol% Pp18-lipids can perform effective PDT and fluorescence imaging. The Pp18-lipos with 65 mol% Pp18 can perform potent PTT and photoacoustic imaging. The chelation of Mn²⁺ endows the Pp18-lipids-Mn²⁺ a high T₁-weighted magnetic resonance imaging contrast. Notably, pretreatment of low-dose PDT facilitates the endocytosis and tumor accumulation of Pp18-lipos, thus achieving synergistic PDT/PTT. Upon exposure to a single 705 nm-laser, the combination of PDT/PTT achieves a significantly higher tumor growth inhibition rate than PDT or PTT alone. In addition, it is found that the synergistic PDT/PTT triggers more potent anti-tumor immune response including tumor infiltration of immune cells and release of related cytokines.     

A Single Molecule Drug Targeting Photosensitizer for Enhanced Breast Cancer Photothermal Therapy

Targeting is one of the most important strategies for enhancing the efficacy of cancer photothermal therapy (PTT) and reducing damage to surrounding normal tissues. Compared with the traditional targeting approaches, the active targeting of breast cancer cells in PTT using chemotherapeutic drugs, such as tamoxifen (TAM), in combination with single‐molecule photothermal photosensitizers has superior selectivity and therapeutic effects. However, single‐molecule drug‐targeting photosensitizers for improved PTT efficacy are not widely reported. Accordingly, herein, a near‐infrared induced small‐molecule photothermal photosensitizer (CyT) is developed that actively targets the estrogen receptors (ERs) of breast cancer cells as well as targets mitochondria by structure‐inherent targeting. Cell uptake and cytotoxicity studies using different types of cells show that CyT enhances the efficiency of TAM‐based PTT by targeting ER‐overexpressing breast cancer cells and selectively killing them. In vivo experiments demonstrate that CyT can be used as a photothermal agent for fluorescence imaging‐guided PTT. More importantly, the intravenous injection of CyT results in better targeting and efficiency of tumor inhibition compared with that achieved with the TAM‐free control molecule Cy. Thus, the study presents an excellent small‐molecule photothermal agent for breast cancer therapy with potential clinical application prospects.     

Activatable Hybrid Nanotheranostics for Tetramodal Imaging and Synergistic Photothermal/Photodynamic Therapy

A multifunctional core–satellite nanoconstruct is designed by assembling copper sulfide (CuS) nanoparticles on the surface of [⁸⁹Zr]‐labeled hollow mesoporous silica nanoshells filled with porphyrin molecules, for effective cancer imaging and therapy. The hybrid nanotheranostic demonstrates three significant features: (1) simple and robust construction from biocompatible building blocks, demonstrating prolonged blood retention, enhanced tumor accumulation, and minimal long‐term systemic toxicity, (2) rationally selected functional moieties that interact together to enable simultaneous tetramodal (positron emission tomography/fluorescence/Cerenkov luminescence/Cerenkov radiation energy transfer) imaging for rapid and accurate delineation of tumors and multimodal image‐guided therapy in vivo, and (3) synergistic interaction between CuS‐mediated photothermal therapy and porphyrin‐mediated photodynamic therapy which results in complete tumor elimination within a day of treatment with no visible recurrence or side effects. Overall, this proof‐of‐concept study illustrates an efficient, generalized approach to design high‐performance core–satellite nanohybrids that can be easily tailored to combine a wide variety of imaging and therapeutic modalities for improved and personalized cancer theranostics in the future.     

Molecular Targeting‐Mediated Mild‐Temperature Photothermal Therapy with a Smart Albumin‐Based Nanodrug

Photothermal therapy (PTT) usually requires hyperthermia >50 °C for effective tumor ablation, which inevitably induces heating damage to the surrounding normal tissues/organs. Moreover, low tumor retention and high liver accumulation are the two main obstacles that significantly limit the efficacy and safety of many nanomedicines. To solve these problems, a smart albumin‐based tumor microenvironment‐responsive nanoagent is designed via the self‐assembly of human serum albumin (HSA), dc‐IR825 (a cyanine dye and a photothermal agent), and gambogic acid (GA, a heat shock protein 90 (HSP90) inhibitor and an anticancer agent) to realize molecular targeting‐mediated mild‐temperature PTT. The formed HSA/dc‐IR825/GA nanoparticles (NPs) can escape from mitochondria to the cytosol through mitochondrial disruption under near‐infrared (NIR) laser irradiation. Moreover, the GA molecules block the hyperthermia‐induced overexpression of HSP90, achieving the reduced thermoresistance of tumor cells and effective PTT at a mild temperature (<45 °C). Furthermore, HSA/dc‐IR825/GA NPs show pH‐responsive charge reversal, effective tumor accumulation, and negligible liver deposition, ultimately facilitating synergistic mild‐temperature PTT and chemotherapy. Taken together, the NIR‐activated NPs allow the release of molecular drugs more precisely, ablate tumors more effectively, and inhibit cancer metastasis more persistently, which will advance the development of novel mild‐temperature PTT‐based combination strategies.     

Core–Satellite Polydopamine–Gadolinium‐Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging‐guided therapy. However, most gadolinium (Gd)–chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released‐Gd‐ions‐associated toxicity. Herein, a radionuclide‐⁶⁴Cu‐labeled doxorubicin‐loaded polydopamine (PDA)–gadolinium‐metallofullerene core–satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging‐guided combination cancer therapy. In this system, the near‐infrared (NIR)‐absorbing PDA acts as a platform for the assembly of different moieties; Gd₃N@C₈₀, a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as‐prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r ₁ = 14.06 mM^?1 s^?1), low risk of release of Gd ions, and NIR‐triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo‐photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.     

A Porphyrin‐Based Conjugated Polymer for Highly Efficient In Vitro and In Vivo Photothermal Therapy

Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor–acceptor (D–A) structured porphyrin‐containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D–A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state‐of‐art porphyrin‐based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 × 10⁴m ^?1 cm^?1 at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer‐based photothermal therapeutic materials for potential personalized theranostic nanomedicine.     

A Comparative Study of Clinical Intervention and Interventional Photothermal Therapy for Pancreatic Cancer

Although nanoparticle‐based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine‐125 (¹²⁵I) interstitial brachytherapy (IBT‐125‐I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti‐urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT‐125‐I, a 25% higher median survival rate of IPTT with complete ablation by one‐time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients.     

Functionalized Graphene@Gold Nanostar/Lipid for Pancreatic Cancer Gene and Photothermal Synergistic Therapy under Photoacoustic/Photothermal Imaging Dual‐Modal Guidance

Nanomaterial‐based pancreatic cancer treatment has received widespread attention and rapid development in the past few years. The major challenges include the poor combination of diagnosis and therapy, the difficulty in targeting therapy from the root and the unsatisfactory antitumor efficiency, which is accompanied by a great risk of relapse and metastasis. In this work, a positively charged lipid bilayer membrane is coated on reduced graphene oxide@gold nanostar (rGO@AuNS) for photoacoustic/photothermal dual‐modal imaging‐guided gene/photothermal synergistic therapy of pancreatic cancer. In addition, the cross‐linking of folic acid on the surface of rGO@AuNS‐lipid can specifically bind after recognizing folic acid receptors on the surface of cancer cells, and greatly improve the targeting ability of the nanomaterial and the performance of imaging diagnosis by receptor‐mediated endocytosis. Moreover, the photothermal and gene (targeting G12V mutant K‐Ras gene) synergistic therapy shows outstanding anticancer efficacy for pancreatic cancer tumor bearing mice, and it is noteworthy that the treatment groups have anti‐liver metastasis of pancreatic cancer.     

Activating Antitumor Immunity and Antimetastatic Effect Through Polydopamine‐Encapsulated Core–Shell Upconversion Nanoparticles

Synergistic phototherapy has the potential to conquer the extreme heterogeneity and complexity of difficult tumors and result in better cancer treatment outcomes than monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). However, the previous approaches to combining PDT and PTT are mainly focused on primary tumor obliteration while neglecting tumor metastasis, which is responsible for about 90% of cancer deaths. It is shown that a combined PDT/PTT approach, based on upconversion‐polymer hybrid nanoparticles with surface‐loaded chlorin e6 photosensitizer, can enhance primary tumor elimination and elicit antitumor immunity against disseminated tumors. The specifical arrangement of an external upconversion coating over the polymer core ensures adequate photoabsorption by the upconversion nanoparticles for the generation of reactive oxygen species upon single near‐infrared light irradiation. Furthermore, it is found that synergistic phototherapy can elicit robust systemic and humoral antitumor immune responses. When combined with immune checkpoint blockades, it can inhibit tumor relapse and metastasis as well as prolong the survival of tumor‐bearing mice in two types of tumor metastasis models. This study may establish a new modality for enhancing immunogenic cell death through a synergistic phototherapeutic nanoplatform and extend this strategy to overcome tumor metastasis with an augmented antitumor immune response.     

NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging‐guided therapy of cancer. In this work, a near‐infrared (NIR)‐triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two‐armed ethanolamine‐modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD‐PGEA) has been successfully fabricated for multimodal imaging‐guided triple‐combination treatment of cancer. A hierarchical hetero‐structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X‐ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl‐rich CD‐PGEA/pDNA complexes, realizing the co‐delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR‐triggered release of DOX through the facilitated detachment of CD‐PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging‐guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.     

Photoconversion‐Tunable Fluorophore Vesicles for Wavelength‐Dependent Photoinduced Cancer Therapy

Photoconversion tunability of fluorophore dye is of great interest in cancer nanomedicine such as fluorescence imaging, photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, this paper reports wavelength‐dependent photoconversional polymeric vesicles of boron dipyrromethene (Bodipy) fluorophore for either PDT under 660 nm irradiation or PTT under 785 nm irradiation. After being assembled within polymeric vesicles at a high drug loading, Bodipy molecules aggregate in the conformations of both J‐type and H‐type, thereby causing red‐shifted absorption into near‐infrared region, ultralow radiative transition, and ideal resistance to photobleaching. Such vesicles further possess enhanced blood circulation, preferable tumor accumulation, as well as superior cell uptake as compared to free Bodipy. In particular, the vesicles mainly generate abundant intracellular singlet oxygen for PDT treatment under 660 nm irradiation, while they primarily produce a potent hyperthermia for PTT with tumor ablation through singlet oxygen‐synergized photothermal necrosis under 785 nm irradiation. This approach provides a facile and general strategy to tune photoconversion characteristics of fluorophore dyes for wavelength‐dependent photoinduced cancer therapy.     

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging‐Guided Synergistic Therapy

Self‐assembly of gold nanoparticles demonstrates a promising approach to realize enhanced photoacoustic imaging (PAI) and photothermal therapy (PTT) for accurate diagnosis and efficient cancer therapy. Herein, unique photothermal assemblies with tunable patterns of gold nanoparticles (including arcs, rings, ribbons, and vesicles) on poly(lactic‐co‐glycolic acid) (PLGA) spheres are constructed taking advantage of emulsion‐confined and polymer‐directed self‐assembly strategies. The influencing factors and formation mechanism to produce the assemblies are investigated in details. Both the emulsion structure and migration behaviors of amphiphilic block copolymer tethered gold nanoparticles are found to contribute to the formation of versatile photothermal assemblies. Hyaluronic acid‐modified R‐PLGA‐Au (RPA) exhibits outstanding photothermal performances under NIR laser irradiation, which is induced by strong plasmonic coupling between adjacent gold nanoparticles. It is interesting that secondary assembly of RPA can be triggered by NIR laser irradiation. Prolonged residence time in tumors is achieved after RPA assemblies are fused into superstructures with larger sizes, realizing real‐time monitoring of the therapeutic processes via PAI with enhanced photoacoustic signals. Notably, synergistic effect resulting from PTT‐enhanced chemotherapy is realized to demonstrate high antitumor performance. This work provides a facile strategy to construct flexible photothermal assemblies with favorable properties for imaging‐guided synergistic therapy.     

Layered MoS2 Hollow Spheres for Highly‐Efficient Photothermal Therapy of Rabbit Liver Orthotopic Transplantation Tumors

Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand‐new MoS₂ nanostructure is designed and fabricated, i.e., layered MoS₂ hollow spheres (LMHSs) with strong absorption in near‐infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as‐prepared LMHSs exhibit unique electronic properties comparing with MoS₂ nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX₂ tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor‐targeting delivery and cancer theranostic application.