Poly(N‐phenylglycine)‐Based Nanoparticles as Highly Effective and Targeted Near‐Infrared Photothermal Therapy/Photodynamic Therapeutic Agents for Malignant Melanoma

Malignant melanoma is a highly aggressive tumor resistant to chemotherapy. Therefore, the development of new highly effective therapeutic agents for the treatment of malignant melanoma is highly desirable. In this study, a new class of polymeric photothermal agents based on poly(N‐phenylglycine) (PNPG) suitable for use in near‐infrared (NIR) phototherapy of malignant melanoma is designed and developed. PNPG is obtained via polymerization of N‐phenylglycine (NPG). Carboxylate functionality of NPG allows building multifunctional systems using covalent bonding. This approach avoids complicated issues typically associated with preparation of polymeric photothermal agents. Moreover, PNPG skeleton exhibits pH‐responsive NIR absorption and an ability to generate reactive oxygen species, which makes its derivatives attractive photothermal therapy (PTT)/photodynamic therapy (PDT) dual‐modal agents with pH‐responsive features. PNPG is modified using hyaluronic acid (HA) and polyethylene glycol diamine (PEG‐diamine) acting as the coupling agent. The resultant HA‐modified PNPG (PNPG‐PEG‐HA) shows negligible cytotoxicity and effectively targets CD44‐overexpressing cancer cells. Furthermore, the results of in vitro and in vivo experiments reveal that PNPG‐PEG‐HA selectively kills B16 cells and suppresses malignant melanoma tumor growth upon exposure to NIR light (808 nm), indicating that PNPG‐PEG‐HA can serve as a very promising nanoplatform for targeted dual‐modality PTT/PDT of melanoma.     

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.     

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.     

ACPI Conjugated Gold Nanorods as Nanoplatform for Dual Image Guided Activatable Photodynamic and Photothermal Combined Therapy In Vivo

The nanoplatform GNR‐ACPP‐PpIX (designated as GNR‐ACPI) is designed for dual image guided combined activatable photodynamic therapy (PDT) and photothermal therapy (PTT). In GNR‐ACPI, gold nanorods (GNRs) are modified with a protoporphyrin (PpIX, a PDT agent) conjugated activatable cell penetrating peptide (ACPP), which consists of the matrix metalloproteinases‐2 (MMP‐2) sensitive peptide sequence GPLGLAG. First, the photoactivity of PpIX is effectively quenched by GNRs due to the strong near infrared region light absorption of GNR and the special “U type” structure of ACPP induced close contact between PpIX and GNR. However, once arriving at the tumor site, the GPLGLAG sequence is hydrolyzed by the MMP‐2 overexpressed by tumor cells, resulting in the release of the residual cell membrane penetrating peptide (CPP) attached PpIX (CPP‐PpIX) with the recovery of photoactivity of PpIX. In addition, with the help of CPP, more efficient cellular uptake of PpIX by tumor cells can be achieved, which will greatly improve the PDT efficacy. Moreover, the GNR can also be utilized for photothermic imaging as well as PTT for tumors. It is found that the combination of PTT and PDT under the guidance of dual‐mode imaging greatly enhances the antitumor effects, while possessing negligible systematic toxicity.     

1D Coordination Polymer Nanofibers for Low‐Temperature Photothermal Therapy

Near‐infrared (NIR)‐light‐triggered photothermal therapy (PTT) usually requires hyperthermia to >50 °C for effective tumor ablation, which can potentially induce inflammatory disease and heating damage of normal organs nearby, while tumor lesions without sufficient heating (e.g., the internal part) may survive after treatment. Achieving effective tumor killing under relatively low temperatures is thus critical toward successful clinical use of PTT. Herein, we design a simple strategy to fabricate poly(ethylene glycol) (PEG)‐modified one‐dimensional nanoscale coordination polymers (1D‐NCPs) with intrinsic biodegradability, large surface area, pH‐responsive behaviors, and versatile theranostic functions. With NCPs consisting of Mn2+/indocyanine green (ICG) as the example, Mn‐ICG@pHis‐PEG display efficient pH‐responsive tumor retention after systemic administration and then load Gambogic acid (GA), a natural inhibitor of heat‐shock protein 90 (Hsp90) that plays an essential role for cells to resist heating‐induced damage. Such Mn‐ICG@pHis‐PEG/GA under a mild NIR‐triggered heating is able to induce effective apoptosis of tumor cells, realizing low‐temperature PTT (~43 °C) with excellent tumor destruction efficacy. This work not only develops a facile approach to fabricate PEGylated 1D‐NCPs with tumor‐specific pH responsiveness and theranostic functionalities, but also presents a unique low‐temperature PTT strategy to kill cancer in a highly effective and minimally invasive manner.     

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.     

Neoadjuvant Chemotherapy Based on Abraxane/Human Neutrophils Cytopharmaceuticals with Radiotherapy for Gastric Cancer

Gastric cancer remains one of the most lethal cancers with high incidence and mortality worldwide. The majority of gastric cancer patients are those who have first been diagnosed in advanced stage, in which the standard chemo‐radiotherapy produces limited benefit along with severe general toxicity, thus the demand for improved therapeutic efficacy and decreased side effects drives the development of novel therapeutic strategies. Here, a neoadjuvant chemotherapy based on Abraxane/human neutrophils (NEs) cytopharmaceuticals with radiotherapy is presented for effective cancer treatment. Human NEs, the most abundant white blood cells in peripheral blood, are developed to carry Abraxane, the commercial albumin‐bound paclitaxel nanoparticle, to form cytopharmaceuticals (Abraxane/NEs) which have been confirmed to maintain the intrinsic functions of human NEs. The modest radiation is applied not only to exert tumor disruption, but also to increase the release of inflammatory factors which guide the NEs homing to the tumoral sites. These amplified inflammatory factors at tumor sites excessively activate Abraxane/NEs to form neutrophil extracellular traps, along with a burst release of Abraxane to induce superior tumor suppression. This adjuvant chemo‐radiotherapy based on cytopharmaceuticals may provide new opportunities for advanced cancer treatment, which reveals the huge clinical potential of human neutrophils as drug delivery vectors.     

Fast‐Clearable Nanocarriers Conducting Chemo/Photothermal Combination Therapy to Inhibit Recurrence of Malignant Tumors

Inhomogeneous heating by photothermal therapy (PTT) during cancer treatment often results in the recurrence of tumors. Thus, integrating PTT with chemotherapy (CHT) may provide a complementary treatment for enhanced therapeutic efficiency. Herein, this study develops a hollow structured polymer–silica nanohybrid (HPSN) as a nanocarrier to simultaneously deliver the anticancer drug paclitaxel and photothermal agent palladium phthalocyanine to tumors through enhanced permeation and the retention effect. A combinational CHT/PTT therapy on mice bearing aggressive tumor grafts is conducted. The highly malignant tumor model, which recurs after sole treatment of PTT, can be eradicated by the combined CHT/PTT treatment. In addition, most of the off‐targeted HPSN nanocarriers can be excreted through a hepatobiliary pathway in about 10 d. Serology results show that the fast‐clearable HPSN can significantly reduce the side effect of the loaded paclitaxel drug. The present work provides an alternative approach for combinational cancer treatment with high therapeutic efficiency.     

Rhenium‐188 Labeled Tungsten Disulfide Nanoflakes for Self‐Sensitized,Near‐Infrared Enhanced Radioisotope Therapy

Radioisotope therapy (RIT), in which radioactive agents are administered or implanted into the body to irradiate tumors from the inside, is a clinically adopted cancer treatment method but still needs improvement to enhance its performances. Herein, it is found that polyethylene glycol (PEG) modified tungsten disulfide (WS₂) nanoflakes can be easily labeled by ¹⁸⁸Re, a widely used radioisotope for RIT, upon simple mixing. Like other high‐Z elements acting as radiosensitizers, tungsten in the obtained ¹⁸⁸Re‐WS₂‐PEG would be able to absorb ionization radiation generated from ¹⁸⁸Re, enabling ‘‘self‐sensitization’’ to enhance the efficacy of RIT as demonstrated in carefully designed in vitro experiments of this study. In the meanwhile, the strong NIR absorbance of WS₂‐PEG could be utilized for NIR light‐induced photothermal therapy (PTT), which if applied on tumors would be able to greatly relieve their hypoxia state and help to overcome hypoxia‐associated radioresistance of tumors. Therefore, with ¹⁸⁸Re‐WS₂‐PEG as a multifunctional agent, which shows efficient passive tumor homing after intravenous injection, in vivo self‐sensitized, NIR‐enhanced RIT cancer treatment is realized, achieving excellent tumor killing efficacy in a mouse tumor model. This work presents a new concept of applying nanotechnology in RIT, by delivering radioisotopes into tumors, self‐sensitizing the irradiation‐induced cell damage, and modulating the tumor hypoxia state to further enhance the therapeutic outcomes.     

Ultrastable Near‐Infrared Conjugated‐Polymer Nanoparticles for Dually Photoactive Tumor Inhibition

It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low‐bandgap donor–acceptor (D–A)‐type conjugated‐polymer nanoparticles (CP‐NPs) are developed to afford a highly efficient singlet‐to‐triplet transition and photothermal conversion for near‐infrared (NIR) light‐induced photodynamic (PDT)/photothermal (PTT) treatment. CP‐NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP‐NPs undergo singlet‐to‐triplet intersystem crossing through charge transfer in the excited D–A system and simultaneous nonradiative decay from the electron‐deficient electron acceptor isoindigo derivative under single‐wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP‐NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light‐triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP‐NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof‐of‐concept design of D–A‐type conjugated‐polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive 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.     

A Metal–Polyphenol Network Coated Nanotheranostic System for Metastatic Tumor Treatments

As a characteristic trait of most tumor types, metastasis is the major cause of the death of patients. In this study, a photothermal agent based on gold nanorod is coated with metal (Gd³⁺)‐organic (polyphenol) network to realize combination therapy for metastatic tumors. This nanotheranostic system significantly enhances antitumor therapeutic effects in vitro and in vivo with the combination of photothermal therapy (PTT) and chemotherapy, also can remarkably prevent the invasion and metastasis due to the presence of polyphenol. After the treatment, an 81% decrease in primary tumor volumes and a 58% decrease in lung metastasis are observed. In addition, the good performance in magnetic resonance imaging, computerized tomography, and photothermal imaging of the nanotheranostic system can realize image‐guided therapy. The multifunctional nanotheranostic system will find a great potential in diagnosis and treatment integration in tumor treatments, and broaden the applications of PTT treatment.     

Enhanced Photothermal Therapy through the In Situ Activation of a Temperature and Redox Dual‐Sensitive Nanoreservoir of Triptolide

Photothermal therapy (PTT) has attracted tremendous attention due to its noninvasiveness and localized treatment advantages. However, heat shock proteins (HSPs) associated self‐preservation mechanisms bestow cancer cells thermoresistance to protect them from the damage of PTT. To minimize the thermoresistance of cancer cells and improve the efficacy of PTT, an integrated on‐demand nanoplatform composed of a photothermal conversion core (gold nanorod, GNR), a cargo of a HSPs inhibitor (triptolide, TPL), a mesoporous silica based nanoreservoir, and a photothermal and redox di‐responsive polymer shell is developed. The nanoplatform can be enriched in the tumor site, and internalized into cancer cells, releasing the encapsulated TPL under the trigger of intracellular elevated glutathione and near‐infrared laser irradiation. Ultimately, the liberated TPL could diminish thermoresistance of cancer cells by antagonizing the PTT induced heat shock response via multiple mechanisms to maximize the PTT effect for cancer treatment.     

Multifunctional Conjugated Polymer Nanoparticles for Image‐Guided Photodynamic and Photothermal Therapy

A multifunctional theranostic platform based on conjugated polymer nanoparticles (CPNs) with tumor targeting, fluorescence detection, photodynamic therapy (PDT), and photothermal therapy (PTT) is developed for effective cancer imaging and therapy. Two conjugated polymers, poly[9,9‐bis(2‐(2‐(2‐methoxyethoxy)ethoxy)‐ethyl)fluorenyldivinylene]‐alt‐4,7‐(2,1,3‐benzothiadiazole) with bright red emission and photosensitizing ability and poly[(4,4,9,9‐tetrakis(4‐(octyloxy)phenyl)‐4,9‐dihydro‐s‐indacenol‐dithiophene‐2,7‐diyl)‐alt‐co‐4,9‐bis(thiophen‐2‐yl)‐6,7‐bis(4‐(hexyloxy)phenyl)‐thiadiazolo‐quinoxaline] with strong near‐infrared absorption and excellent photothermal conversion ability are co‐loaded into one single CPN via encapsulation approach using lipid‐polyethylene glycol as the matrix. The obtained co‐loaded CPNs show sizes of around 30 nm with a high singlet oxygen quantum yield of 60.4% and an effective photothermal conversion efficiency of 47.6%. The CPN surface is further decorated with anti‐HER2 affibody, which bestows the resultant anti‐HER2‐CPNs superior selectivity toward tumor cells with HER2 overexpression both in vitro and in vivo. Under light irradiation, the PDT and PTT show synergistic therapeutic efficacy, which provides new opportunities for the development of multifunctional biocompatible organic materials in cancer therapy.     

J‐Aggregates of Organic Dye Molecules Complexed with Iron Oxide Nanoparticles for Imaging‐Guided Photothermal Therapy Under 915‐nm Light

Recently, the development of nano‐theranostic agents aiming at imaging guided therapy has received great attention. In this work, a near‐infrared (NIR) heptamethine indocyanine dye, IR825, in the presence of cationic polymer, polyallylamine hydrochloride (PAH), forms J‐aggregates with red‐shifted and significantly enhanced absorbance. After further complexing with ultra‐small iron oxide nanoparticles (IONPs) and the followed functionalization with polyethylene glycol (PEG), the obtained IR825@PAH‐IONP‐PEG composite nanoparticles are highly stable in different physiological media. With a sharp absorbance peak, IR825@PAH‐IONP‐PEG can serve as an effective photothermal agent under laser irradiation at 915 nm, which appears to be optimal in photothermal therapy application considering its improved tissue penetration compared with 808‐nm light and much lower water heating in comparison to 980‐nm light. As revealed by magnetic resonance (MR) imaging, those nanoparticles after intravenous injection exhibit high tumor accumulation, which is then harnessed for in vivo photothermal ablation of tumors, achieving excellent therapeutic efficacy in a mouse tumor model. This study demonstrates for the first time that J‐aggregates of organic dye molecules are an interesting class of photothermal material, which when combined with other imageable nanoprobes could serve as a theranostic agent for imaging‐guided photothermal therapy of cancer.     

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.     

Polyaniline Nanovesicles for Photoacoustic Imaging‐Guided Photothermal‐Chemo Synergistic Therapy in the Second Near‐Infrared Window

Photoacoustic imaging‐guided photothermal therapy in the second near‐infrared (NIR‐II) window shows promise for clinical deep‐penetrating tumor phototheranostics. However, ideal photothermal agents in the NIR‐II window are still rare. Here, the emeraldine salt of polyaniline (PANI‐ES), especially synthesized by a one‐pot enzymatic reaction on sodium bis(2‐ethylhexyl) sulfosuccinate (AOT) vesicle surface (PANI‐ES@AOT, λ_max ≈ 1000 nm), exhibits excellent dispersion in physiological environment and remarkable photothermal ability at pH 6.5 (photothermal conversion efficiency of 43.9%). As a consequence of the enhanced permeability and retention effect of tumors and the doping‐induced photothermal effect of PANI‐ES@AOT, this pH‐sensitive NIR‐II photothermal agent allows tumor acidity phototheranostics with minimized pseudosignal readout and subdued normal tissue damage. Moreover, the enhanced fluidity of vesicle membrane triggered by heating is beneficial for drug release and allows precise synergistic therapy for an improved therapeutic effect. This study highlights the potential of template‐oriented (or interface‐confined) enzymatic polymerization reactions for the construction of conjugated polymers with desired biomedical applications.     

A minimally designed PD-L1-targeted nanocomposite for positive feedback-based multimodal cancer therapy

Combining immune checkpoint blockade therapy (ICBT) with other treatment modalities through nanotechnology offers an opportunity to further boost immunity for effective cancer treatment. Herein three-in-one programmed death-ligand 1 (PD-L1)-targeted nanocomposite (NC) was minimally fabricated through self-assembling photothermal agent black phosphorus nanosheet (BPN), chemotherapeutic agent Polymetformin (PolyMet), and immune checkpoint inhibitor anti-PD-L1 antibody (aPD-L1), avoiding the easy degradability of BPN through bridging the electrostatic interaction between PolyMet and BPN. The prepared aPD-L1-PolyMet/BPN NC could precisely target primary tumor through the interaction between aPD-L1 and PD-L1 based on ICBT, and the targeting efficacy was gradually reinforced due to the PD-L1 upregulation in tumor sites after photothermal therapy (PTT), ensuring positive feedback-mediated multimodal antitumor effect during continuous treatment loops. Moreover, the combinational therapy composed of photothermal immunotherapy (PIT), chemotherapy and ICBT strengthened the antitumor efficacy owing to their synergistic mechanism. Meanwhile, the generated positive feedback property during treatment displayed powerful antitumor effect, which not only inhibited primary and abscopal tumor progression, but also prevented tumor metastasis and promoted long-term tumor immune memory establishment. Therefore, this antitumor NC provided a prospective insight into the field of multimodal cancer therapy through rational and minimal design.     

A Self‐Assembled DNA Origami‐Gold Nanorod Complex for Cancer Theranostics

A self‐assembled DNA origami (DO)‐gold nanorod (GNR) complex, which is a dual‐functional nanotheranostics constructed by decorating GNRs onto the surface of DNA origami, is demonstrated. After 24 h incubation of two structured DO‐GNR complexes with human MCF7 breast cancer cells, significant enhancement of cell uptake is achieved compared to bare GNRs by two‐photon luminescence imaging. Particularly, the triangle shaped DO‐GNR complex exhibits optimal cellular accumulation. Compared to GNRs, improved photothermolysis against tumor cells is accomplished for the triangle DO‐GNR complex by two‐photon laser or NIR laser irradiation. Moreover, the DO‐GNR complex exhibits enhanced antitumor efficacy compared with bare GNRs in nude mice bearing breast tumor xenografts. The results demonstrate that the DO‐GNR complex can achieve optimal two‐photon cell imaging and photothermal effect, suggesting a promising candidate for cancer diagnosis and therapy both in vitro and in vivo.     

Glutathione Depletion in a Benign Manner by MoS2‐Based Nanoflowers for Enhanced Hypoxia‐Irrelevant Free‐Radical‐Based Cancer Therapy

Tumor hypoxia significantly diminishes the efficacy of reactive oxygen species (ROS)‐based therapy, mainly because the generation of ROS is highly oxygen dependent. Recently reported hypoxia‐irrelevant radical initiators (AIBIs) exhibit promising potential for cancer therapy under different oxygen tensions. However, overexpressed glutathione (GSH) in cancer cells would potently scavenge the free radicals produced from AIBI before their arrival to the specific site and dramatically limit the therapeutic efficacy. A synergistic antitumor platform (MoS₂@AIBI‐PCM nanoflowers) is constructed by incorporating polyethylene‐glycol‐functionalized molybdenum disulfide (PEG‐MoS₂) nanoflowers with azo initiator and phase‐change material (PCM). Under near‐infrared laser (NIR) irradiation, the photothermal feature of PEG‐MoS₂ induces the decomposition of AIBI to produce free radicals. Furthermore, PEG‐MoS₂ can facilitate GSH oxidation without releasing toxic metal ions, greatly promoting tumor apoptosis and avoiding the introduction of toxic metal ions. This is the first example of the use of intelligent MoS₂‐based nanoflowers as a benign GSH scavenger for enhanced cancer treatment.