Tantalum Sulfide Nanosheets as a Theranostic Nanoplatform for Computed Tomography Imaging‐Guided Combinatorial Chemo‐Photothermal Therapy

Near‐infrared (NIR)‐absorbing metal‐based nanomaterials have shown tremendous potential for cancer therapy, given their facile and controllable synthesis, efficient photothermal conversion, capability of spatiotemporal‐controlled drug delivery, and intrinsic imaging function. Tantalum (Ta) is among the most biocompatible metals and arouses negligible adverse biological responses in either oxidized or reduced forms, and thus Ta‐derived nanomaterials represent promising candidates for biomedical applications. However, Ta‐based nanomaterials by themselves have not been explored for NIR‐mediated photothermal ablation therapy. In this work, an innovative Ta‐based multifunctional nanoplatform composed of biocompatible tantalum sulfide (TaS₂) nanosheets (NSs) is reported for simultaneous NIR hyperthermia, drug delivery, and computed tomography (CT) imaging. The TaS₂ NSs exhibit multiple unique features including (i) efficient NIR light‐to‐heat conversion with a high photothermal conversion efficiency of 39%, (ii) high drug loading (177% by weight), (iii) controlled drug release triggered by NIR light and moderate acidic pH, (iv) high tumor accumulation via heat‐enhanced tumor vascular permeability, (v) complete tumor ablation and negligible side effects, and (vi) comparable CT imaging contrast efficiency to the widely clinically used agent iobitridol. It is expected that this multifunctional NS platform can serve as a promising candidate for imaging‐guided cancer therapy and selection of cancer patients with high tumor accumulation.     

Size‐Transformable Metal–Organic Framework–Derived Nanocarbons for Localized Chemo‐Photothermal Bacterial Ablation and Wound Disinfection

Severe infectious diseases caused by pathogenic bacteria have become urgent threats to global public health. Antibacterial materials with combined chemo‐photothermal therapeutic capabilities possess distinct advantages when compared with many other antibacterial approaches. However, developing simplified and chemically tunable precursors to synthesize such antibacterial nanoagents for rapidly, safely, and synergistically combating pathogenic bacteria remains a huge challenge. Herein, metal–organic framework (MOF)‐derived nanocarbons with near‐infrared (NIR)‐responsive and size‐transformable capabilities are designed to overcome this challenge. The MOF‐derived nanocarbons with chemo‐photothermal bactericidal capabilities are first synthesized, and then coated with a thermoresponsive gel layer to obtain ON–OFF switching capability for bacterial trapping. The fabricated nanocarbons exhibit high photo‐to‐thermal conversion efficiency and fast size transformation from nanodispersions to micrometer aggregations upon NIR irradiation, thus enabling nanocarbons to generate localized massive heat and abundant Zn²⁺ ions for directly disrupting bacterial membrane and intracellular proteins. Furthermore, these nanocarbons not only exhibit a nearly 100% bactericidal ratio at very low dosage, but also possess highly efficient and safe wound disinfection activities, which are comparable to vancomycin. Overall, these proposed novel nanocarbons display robust and localized chemo‐photothermal bactericidal capability and possess great potential to be used as alternative to antibiotics for broad‐spectrum eradication of pathogenic bacteria.     

All‐in‐One Phototheranostics: Single Laser Triggers NIR‐II Fluorescence/Photoacoustic Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy

Development of single near‐infrared (NIR) laser triggered phototheranostics for multimodal imaging guided combination therapy is highly desirable but is still a big challenge. Herein, a novel small‐molecule dye DPP‐BT is designed and synthesized, which shows strong absorption in the first NIR window (NIR‐I) and fluorescence emission in the second NIR region (NIR‐II). Such a dye not only acts as a dual‐modal contrast agent for NIR‐II fluorescence and photoacoustic (PA) imaging, but also serves as a combined therapeutic agent for photothermal therapy (PTT) and photodynamic therapy (PDT). The single NIR laser triggered all‐in‐one phototheranostic nanoparticles are constructed by encapsulating the dye DPP‐BT, chemotherapy drug DOX, and natural phase‐change materials with a folic acid functionalized amphiphile. Notably, under NIR laser irradiation, DOX can effectively release from such nanoparticles via NIR‐induced hyperthermia of DPP‐BT. By intravenous injection of such nanoparticles into Hela tumor‐bearing mice, the tumor size and location can be accurately observed via NIR‐II fluorescence/PA dual‐modal imaging. From in vitro and in vivo therapy results, such nanoparticles simultaneously present remarkable antitumor efficacy by PTT/PDT/chemo combination therapy, which is triggered by a single NIR laser. Overall, this work provides an innovative strategy to design and construct all‐in‐one nanoplatforms for clinical phototheranostics.     

Near‐Infrared Light‐Absorptive Stealth Liposomes for Localized Photothermal Ablation of Tumors Combined with Chemotherapy

Although near‐infrared (NIR) light‐absorbing organic dyes have recently been proposed for photothermal ablation of tumors, their clinical applications have often been hampered by problems such as low water solubility and minimal tissue absorption. Rapid development of nanotechnology provides various novel nanostructures to address these issues. In this work, doxorubicin (DOX)‐loaded stealth liposomes are engineered through the incorporation of an NIR‐absorptive heptamethine indocyanine dye IR825 into the thermoresponsive liposomes for photothermal/chemo combined cancer therapy. It is demonstrated that the lipid nanostructure can enhance the bioavailability of water‐insoluble IR825 for efficient photothermal treatment, while delivering the anticancer drug doxorubicin to achieve simultaneous anticancer medication. The combined treatment of photothermal ablation and chemotherapy synergistically improves the overall cancer cell killing efficiency, which can be of future clinical interest.     

SnTe@MnO2‐SP Nanosheet–Based Intelligent Nanoplatform for Second Near‐Infrared Light–Mediated Cancer Theranostics

Near infrared light, especially the second near‐infrared light (NIR II) biowindows with deep penetration and high sensitivity are widely used for optical diagnosis and phototherapy. Here, a novel kind of 2D SnTe@MnO₂‐SP nanosheet (NS)‐based nanoplatform is developed for cancer theranostics with NIR II‐mediated precise optical imaging and effective photothermal ablation of mouse xenografted tumors. The 2D SnTe@MnO₂‐SP NSs are fabricated via a facile method combining ball‐milling and liquid exfoliation for synthesis of SnTe NSs, and surface coating MnO₂ shell and soybean phospholipid (SP). The ultrathin SnTe@MnO₂‐SP NSs reveal notably high photothermal conversion efficiency (38.2% in NIR I and 43.9% in NIR II). The SnTe@MnO₂‐SP NSs inherently feature tumor microenvironment (TME)‐responsive biodegradability, and the main metabolite TeO₃^2? shows great antitumor effect, coupling synergetic chemotherapy for cancer. Moreover, the SnTe@MnO₂‐SP NSs also exhibit great potential for fluorescence, photoacoustic (PA), and photothermal imaging agents in the NIR II biowindow with much higher resolution and sensitivity. This is the first report, as far as is known, with such an inorganic nanoagent setting fluorescence/PA/photothermal imaging and photothermal therapy in NIR II biowindow and TME‐responsive biodegradability rolled into one, which provide insight into the clinical potential for cancer theranostics.     

Light‐Activatable Assembled Nanoparticles to Improve Tumor Penetration and Eradicate Metastasis in Triple Negative Breast Cancer

Triple‐negative breast cancer (TNBC) is a kind of aggressive malignancy with fast metastatic behavior. Herein, a nanosystem loaded with a near‐infrared (NIR) agent is developed to achieve chemo‐photothermal combination therapy for inhibiting tumor growth and metastasis in TNBC. The NIR agent of ultrasmall sized copper sulfide nanodots with strong NIR light‐absorbing capability is entrapped into the doxorubicin‐contained temperature‐sensitive polymer‐based nanosystem by a self‐assembled method. The temperature sensitive nanoclusters (TSNCs) can significantly enhance the drug penetration depth and significantly kill the cancer cells under the near‐infrared laser irradiation. Importantly, it is plausible that the tumor penetrating nanosystem combined with NIR laser irradiation can prevent lung and liver metastasis via extermination of the cancer stem cells. The in vivo characteristics, evaluated by photoacoustic imaging, pharmacokinetics, and biodistribution, confirm their feasibility for tumor treatment owing to their long blood circulation time and high tumor uptake. Thanks to the high tumor uptake and highly potent antitumor efficacy, the doxorubicin‐induced cardiotoxicity can be avoided when the TSNC is used. Taken together, it is believed that the nanosystem has excellent potential for clinical translation.     

High‐Security Multifunctional Nano‐Bismuth‐Sphere‐Cluster Prepared from Oral Gastric Drug for CT/PA Dual‐Mode Imaging and Chemo‐Photothermal Combined Therapy In Vivo

Multifunctional nanoprobes that can be applied for real‐time monitoring or precision treatment of tumors have received wide interest among researchers. However, most of these nanoprobes are obtained through chemical synthesis, and thereby may contain toxic residues or harmful reagents. In this article, a nano‐bismuth‐sphere‐cluster (Bi) is synthesized via a one‐step method (after an irradiation with ultra‐violet) and is then applied in dual‐mode computed tomography/photoacoustic imaging. Bismuth potassium citrate granules, which is a common gastric drug that is highly safe and has a low price (<1 China Yuan/g), is used as the only raw material. The results show that the Bi cluster has good stability with sizes of about 25–55 nm, and a photothermal conversion efficiency as high as 39.67%. After being adsorbed onto doxorubicin, the Bi cluster can be used directly in animal experiments. Due to the effect of enhanced permeability and retention, the probe can easily enter tumor cells. Drug release can be controlled by a near‐infrared laser and the acidic environment of tumor cells, which indicates that the combined chemo‐photothermal therapy is achieved. This work presents a new dual‐mode bio‐imaging and combined chemo‐photothermal therapeutic nanoprobe that can be applied in theragnostics for tumors.     

Cancer Cell Membrane‐Coated Gold Nanocages with Hyperthermia‐Triggered Drug Release and Homotypic Target Inhibit Growth and Metastasis of Breast Cancer

The cell‐specific targeting drug delivery and controlled release of drug at the cancer cells are still the main challenges for anti‐breast cancer metastasis therapy. Herein, the authors first report a biomimetic drug delivery system composed of doxorubicin (DOX)‐loaded gold nanocages (AuNs) as the inner cores and 4T1 cancer cell membranes (CMVs) as the outer shells (coated surface of DOX‐incorporated AuNs (CDAuNs)). The CDAuNs, perfectly utilizing the natural cancer cell membranes with the homotypic targeting and hyperthermia‐responsive ability to cap the DAuNs with the photothermal property, can realize the selective targeting of the homotypic tumor cells, hyperthermia‐triggered drug release under the near‐infrared laser irradiation, and the combination of chemo/photothermal therapy. The CDAuNs exhibit a stimuli‐release of DOX under the hyperthermia and a high cell‐specific targeting of the 4T1 cells in vitro. Moreover, the excellent combinational therapy with about 98.9% and 98.5% inhibiting rates of the tumor volume and metastatic nodules is observed in the 4T1 orthotopic mammary tumor models. As a result, CDAuNs can be a promising nanodelivery system for the future therapy of breast cancer.     

Ultrasmall Semiconducting Polymer Dots with Rapid Clearance for Second Near‐Infrared Photoacoustic Imaging and Photothermal Cancer Therapy

Phototheranostic agents in the second near‐infrared (NIR‐II) window (1000–1700 nm) are emerging as a promising theranostic platform for precision medicine due to enhanced penetration depth and minimized tissue exposure. The development of metabolizable NIR‐II nanoagents for imaging‐guided therapy are essential for noninvasive disease diagnosis and precise ablation of tumors. Herein, metabolizable highly absorbing NIR‐II conjugated polymer dots (Pdots) are reported for the first time for photoacoustic imaging guided photothermal therapy (PTT). The unique design of low‐bandgap D‐A π‐conjugated polymer (DPP‐BTzTD) together with modified nanoreprecipitation conditions allows to fabricate NIR‐II absorbing Pdots with ultrasmall (4 nm) particle size. Extensive experimental tests demonstrate that the constructed Pdots exhibit good biocompatibility, excellent photostability, bright photoacoustic signals, and high photothermal conversion efficiency (53%). In addition, upon tail‐vein intravenous injection of tumor‐bearing mice, Pdots also show high‐efficient tumor ablation capability with rapid excretion from the body. In particular, both in vitro and in vivo assays indicate that the Pdots possess remarkable PTT performance under irradiation with a 1064 nm laser with 0.5 W cm^?2, which is much lower than its maximum permissible exposure limit of 1 W cm^?2. This pilot study thus paves a novel avenue for the development of organic semiconducting nanoagents for future clinical translation.     

Gold Nanorods Electrostatically Binding Nucleic Acid Probe for In Vivo MicroRNA Amplified Detection and Photoacoustic Imaging‐Guided Photothermal Therapy

Developing a comprehensive platform which has both diagnosis and therapeutic strategies is necessary for efficient tumor treatment. In this work, a F uel I mproved micro R NA E xplorer (FIRE) probe with signal amplification capability is designed for sensitive detection of microRNA‐21 (miR‐21), which is upregulated in most tumor cells. Besides, FIRE could be loaded by polyethylenimine (PEI)‐modified gold nanorods (AuNR‐PEI) via facile electrostatic interaction, which could avoid the complicated processes commonly used to covalently conjugate nucleic acid probes onto AuNRs. The as‐fabricated AuNR‐PEI/FIRE system could efficiently distinguish tumor cells from non‐tumor cells. The fluorescence signals in MCF‐7 breast carcinoma and HeLa cervical carcinoma cells treated with AuNR‐PEI/FIRE are enhanced 7‐ and 4.5‐fold, respectively, compared with non‐amplification system. AuNR‐PEI/FIRE improves tumor detection ability in vivo and exhibits excellent tumor inhibition efficacy under the fluorescence imaging and photoacoustic imaging guided photothermal therapy. This is the first time to utilize the combined application of amplified nucleic acid detection and photothermal effect derived from gold nanorods together with PA imaging in a facile manner to provide a promising theranostic strategy for accurate diagnosis and tumor therapy.     

Tumor‐Penetrating Nanotherapeutics Loading a Near‐Infrared Probe Inhibit Growth and Metastasis of Breast Cancer

The tumor growth and metastasis is the leading reason for the high mortality of breast cancer. Herein, it is first reported a deep tumor‐penetrating photothermal nanotherapeutics loading a near‐infrared (NIR) probe for potential photothermal therapy (PTT) of tumor growth and metastasis of breast cancer. The NIR probe of 1,1‐dioctadecyl‐3,3,3,3‐tetramethylindotricarbocyanine iodide (DiR), a lipophilicfluorescent carbocyanine dye with strong light‐absorbing capability, is entrapped into the photothermal nanotherapeutics for PTT application. The DiR‐loaded photothermal nanotherapeutics (DPN) is homogeneous nanometer‐sized particles with the mean diameter of 24.5 ± 4.1 nm. Upon 808 nm laser irradiation, DPN presents superior production of thermal energy than free DiR both in vitro and in vivo. The cell proliferation and migration activities of metastatic 4T1 breast cancer cells are obviously inhibited by DPN in combination with NIR irradiation. Moreover, DPN can induce a higher accumulation in tumor and penetrate into the deep interior of tumor tissues. The in vivo PTT measurements indicate that the growth and metastasis of breast cancer are entirely inhibited by a single treatment of DPN with NIR irradiation. Therefore, the deep tumor‐penetrating DPN can provide a promising strategy for PTT of tumor progression and metastasis of breast cancer.     

High‐Security Nanocluster for Switching Photodynamic Combining Photothermal and Acid‐Induced Drug Compliance Therapy Guided by Multimodal Active‐Targeting Imaging

High‐security nanoplatform with enhanced therapy compliance is extremely promising for tumor. Herein, using a simple and high‐efficient self‐assembly method, a novel active‐targeting nanocluster probe, namely, Ag₂S/chlorin e6 (Ce6)/DOX@DSPE‐mPEG₂₀₀₀‐folate (ACD‐FA) is synthesized. Experiments indicate that ACD‐FA is capable of specifically labeling tumor and guiding targeting ablation of the tumor via precise positioning from fluorescence and photoacoustic imaging. Importantly, the probe is endowed with a photodynamic “on‐off” effect, that is, Ag₂S could effectively quench the fluorescence of chlorin e6 (89.5%) and inhibit release of ¹O₂ (92.7%), which is conducive to avoid unwanted phototoxicity during transhipment in the body, and only after nanocluster endocytosed by tumor cells could release Ce6 to produce ¹O₂. Moreover, ACD‐FA also achieves excellent acid‐responsive drug release, and exhibits eminent chemo‐photothermal and photodynamic effects upon laser irradiation. Compared with single or two treatment combining modalities, ACD‐FA could provide the best cancer therapeutic effect with a relatively low dose, because it made the most of combined effect from chemo‐photothermal and controlled photodynamic therapy, and significantly improves the drug compliance. Besides, the active‐targeting nanocluster notably reduces nonspecific toxicity of both doxorubicin and chlorin e6. Together, this study demonstrates the potency of a newly designed nanocluster for nonradioactive concomitant therapy with precise tumor‐targeting capability.     

pH‐Responsive Cyanine‐Grafted Graphene Oxide for Fluorescence Resonance Energy Transfer‐Enhanced Photothermal Therapy

Stimuli‐responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli‐responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof‐of‐concept, a pH‐responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near‐infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate‐grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH‐dependent FRET effect between GO and Cypate and thus induce pH‐responsive photothermal effect of GO‐Cypate. GO‐Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single‐dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli‐responsive photothermal nanoplatform for cancer therapy.     

PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy

Photothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near‐infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825–PEG nanoparticles show ultra‐high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low‐power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR‐absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.     

A Versatile Nanotheranostic Agent for Efficient Dual‐Mode Imaging Guided Synergistic Chemo‐Thermal Tumor Therapy

The integration of efficient imaging for diagnosis and synergistic tumor therapy into a single‐component nanoplatform is much promising for high efficacy tumor treatment but still in a great challenge. Herein, a smart and versatile nanotheranostic platform based on hollow mesoporous Prussian blue nanoparticles (HMPBs) with perfluoropentane (PFP) and doxorubicin (DOX) inside, has been designed, for the first time, to achieve the distinct in vivo synergistic chemo‐thermal tumor therapy and synchronous diagnosis and monitoring by ultrasound (US)/photoacoustic (PA) dual mode imaging. The prepared HMPBs show excellent photothermal conversion properties with large molar extinction coefficient (≈1.2 × 10¹¹m ^?1 cm^?1) and extremely high photothermal conversion efficiency (41.4%). Such a novel theranostic nanoplatform is expected to overcome the inevitable tumor recurrence and metastasis resulting from the inhomogeneous ablation of single thermal therapy, which will find a promising prospect in the application of noninvasive cancer therapy.     

NIR Light‐Triggered Degradable MoTe2 Nanosheets for Combined Photothermal and Chemotherapy of Cancer

Telluride molybdenum (MoTe₂) nanosheets with wide near‐infrared (NIR) absorbance are functionalized with polyethylene glycol‐cyclic arginine‐glycine‐aspartic acid tripeptide (PEG‐cRGD). After loading a chemotherapeutic drug (doxorubicin, DOX), MoTe₂‐PEG‐cRGD/DOX is used for combined photothermal therapy and chemotherapy. With the high photothermal conversion efficiency, MoTe₂‐PEG‐cRGD/DOX exhibits favorable cells killing ability under NIR irradiation. Owing to the cRGD‐mediated specific tumor targeting, MoTe₂‐PEG‐cRGD/DOX shows efficient accumulation in tumors to induce a strong tumor ablation effect. MoTe₂‐PEG‐cRGD nanosheets, which are relatively stable in the circulation, could be degraded under NIR ray. The in vitro and in vivo experimental results demonstrate that this theranostic nanoagent, which could accumulate in tumors to allow photothermal imaging and combined therapy, is readily degradable in normal organs to enable rapid excretion and avoid long‐term retention/toxicity, holding great potential to treat tumor effectively.     

Engineering Versatile Nanoparticles for Near‐Infrared Light‐Tunable Drug Release and Photothermal Degradation of Amyloid β

Nanomedicines that inhibit/disassemble amyloid β (Aβ) aggregates in Alzheimer's disease (AD) are highly desirable yet remain challenging. Therapeutic efficacy and systemic delivery of reported molecules and nanoparticles (NPs) are hampered by various challenges, including low biocompatibility, off‐target toxicity, and lack of specificity. Herein, a versatile NP is designed by integrating high Aβ‐binding affinity, stimuli‐responsive drug release, and photothermal degradation properties for efficient disassembly of Aβ. Near‐infrared (NIR)‐absorbing conjugated polymer PDPP3T‐O14 serves as a photothermal core while thermal‐responsive polymer 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine at the outer layer as the NIR‐stimuli gatekeeper. Curcumin, an inhibitor of Aβ aggregation, is loaded into the NP with high encapsulation efficiency. The 5‐mer β‐sheet breaker peptides LPFFD (Leu‐Pro‐Phe‐Phe‐Asp) having high binding affinity toward Aβ are further anchored onto the surface of polyethylene glycol‐lipid shell for active Aβ‐targeting. The resultant NPs exhibit good Aβ‐targeting ability and obvious photothermal dissociation effect together with Aβ aggregation‐dependent fluorescence detection capability. Upon NIR laser irradiation, entrapped curcumin can be effectively released from the unconsolidated NPs to enhance the anti‐amyloid activity. In vitro studies demonstrate that the NPs dramatically lower Aβ‐induced cytotoxicity of PC12 cells, and therefore show great potential for the application in AD treatment.     

Copper(I) Phosphide Nanocrystals for In Situ Self‐Generation Magnetic Resonance Imaging‐Guided Photothermal‐Enhanced Chemodynamic Synergetic Therapy Resisting Deep‐Seated Tumor

Fe‐based Fenton agents can generate highly reactive and toxic hydroxyl radicals (·OH) in the tumor microenvironment (TME) for chemodynamic therapy (CDT) with high specificity. However, the strict condition (lower pH environment: 3–4) of the highly efficient Fenton reaction limits its practical application in the clinic. Development of new CDT agents more suitable for TME is significant and challenging. A highly efficient Cu(I)‐based CDT agent, copper(I) phosphide nanocrystals (CP NCs), which is more adaptable to the pH value of TME than Fe‐based agents, thereby producing more ·OH to trigger the apoptosis of cancer cells, is prepared. Moreover, the excess glutathione (GSH) in TME can reduce the Cu(II) produced by a Fenton‐like reaction to Cu(I), further increasing the generation rate of ·OH and relieving tumor antioxidant ability. Furthermore, owing to their strong absorption in the NIR II region, CP NCs exhibit an excellent photothermal conversion effect, which can further improve the Fenton reaction. What is more, CP NCs can act as in situ self‐generation magnetic resonance imaging (MRI) agents owing to the generation of paramagnetic Cu(II) in response to excess H₂O₂ in the TME. These properties may open up the exploration of copper‐based materials in clinical application of self‐generation imaging‐guided synergetic treatment.     

Long‐Circulating Drug‐Dye‐Based Micelles with Ultrahigh pH‐Sensitivity for Deep Tumor Penetration and Superior Chemo‐Photothermal Therapy

Nanocarriers for chemo‐photothermal therapy suffer from insufficient retention at the tumor site and poor penetration into tumor parenchyma. A smart drug‐dye‐based micelle is designed by making the best of the structural features of small‐molecule drugs. P‐DOX is synthesized by conjugating doxorubicin (DOX) with poly(4‐formylphenyl methacrylate‐co‐2‐(diethylamino) ethyl methacrylate)‐b‐polyoligoethyleneglycol methacrylate (P(FPMA‐co‐DEA)‐b‐POEGMA) via imine linkage. Through the π–π stacking interaction, IR780, a near‐infrared fluorescence dye as well as a photothermal agent, is integrated into the micelles (IR780‐PDMs) with the P‐DOX. The IR780‐PDMs show remarkably long blood circulation (t_1/2β = 22.6 h). As a result, a progressive tumor accumulation and retention are presented, which is significant to the sequential drug release. Moreover, when entering into a moderate acidic tumor microenvironment, IR780‐PDMs can dissociate into small‐size conjugates and IR780, which obviously increases the penetration depth of drugs, and then improves the lethality to deep‐seated tumor cells. Owing to the high delivery efficiency and superior chemo‐photothermal therapeutic efficacy of IR780‐PDMs, 97.6% tumor growth in the A549 tumor‐bearing mice is suppressed with a low dose of intravenous injection (DOX, 1.5 mg kg^?1; IR780, 0.8 mg kg^?1). This work presents a brand‐new strategy for long‐acting intensive cancer therapy.     

Photo‐ and pH‐Triggered Release of Anticancer Drugs from Mesoporous Silica‐Coated Pd@Ag Nanoparticles

A smart drug delivery system integrating both photothermal therapy and chemotherapy for killing cancer cells is reported. The delivery system is based on a mesoporous silica‐coated Pd@Ag nanoplates composite. The Pd@Ag nanoplate core can effectively absorb and convert near infrared (NIR) light into heat. The mesoporous silica shell is provided as the host for loading anticancer drug, doxorubicin (DOX). The mesoporous shell consists of large pores, ～10 nm in diameter, and allows the DOX loading as high as 49% in weight. DOX loaded core–shell nanoparticles exhibit a higher efficiency in killing cancer cells than free DOX. More importantly, DOX molecules are loaded in the mesopores shell through coordination bonds that are responsive to pH and heat. The release of DOX from the core‐shell delivery vehicles into cancer cells can be therefore triggered by the pH drop caused by endocytosis and also NIR irradiation. A synergistic effect of combining chemotherapy and photothermal therapy is observed in our core‐shell drug delivery system. The cell‐killing efficacy by DOX‐loaded core–shell particles under NIR irradiation is higher than the sum of chemotherapy by DOX‐loaded particles and photothermal therapy by core–shell particles without DOX.