First Demonstration of Gold Nanorods‐Mediated Photodynamic Therapeutic Destruction of Tumors via Near Infra‐Red Light Activation

Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1–48 W/cm²) irradiation, leading to hyperthermia‐induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs‐mediated PTT and organic photosensitizers‐mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (¹O₂) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm²) light excitation. By changing the NIR light excitation wavelengths, Au NRs‐mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti‐cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon‐induced fluorescence to illustrate their in vivo locations/distribution.     

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.     

A Multifunctional Cascade Bioreactor Based on Hollow‐Structured Cu2MoS4 for Synergetic Cancer Chemo‐Dynamic Therapy/Starvation Therapy/Phototherapy/Immunotherapy with Remarkably Enhanced Efficacy

The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu₂MoS₄ (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo‐dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu^1+/2+, Mo^4+/6+) exhibit Fenton‐like, glutathione (GSH) peroxidase‐like and catalase‐like activity. Once internalized into the tumor, CMS could generate ·OH for CDT via Fenton‐like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase‐like CMS could react with endogenous H₂O₂ to generate O₂ for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H₂O₂. The regenerated H₂O₂ can devote to Fenton‐like reaction for realizing GOx‐catalysis‐enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor‐killing ability by phototherapy due to its excellent photothermal conversion efficiency (η = 63.3%) and cytotoxic superoxide anion (·O₂^?) generation performance. More importantly, the PEGylated CMS@GOx‐based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.     

Light‐Triggered In Situ Gelation to Enable Robust Photodynamic‐Immunotherapy by Repeated Stimulations

Photodynamic therapy (PDT) has shown the potential of triggering systemic antitumor immune responses. However, while the oxygen‐deficient hypoxic tumor microenvironment is a factor that limits the PDT efficacy, the immune responses after conventional PDT usually are not strong enough to eliminate metastatic tumors. Herein, a light‐triggered in situ gelation system containing photosensitizer‐modified catalase together with poly(ethylene glycol) double acrylate (PEGDA) as the polymeric matrix is designed. Immune adjuvant nanoparticles are further introduced into this system to trigger robust antitumor immune responses after PDT. Following local injection of the mixed precursor solution into tumors and the subsequent light exposure, polymerization of PEGDA can be initiated to induce in situ gelation. Such hybrid hydrogel with long‐term tumor retention of various agents and the ability to enable persistent tumor hypoxia relief can enable multiple rounds of PDT, which results in significantly enhanced immune responses by multiround stimulation. Further combination of such gel‐based multiround PDT with anticytotoxic T‐lymphocyte antigen‐4 checkpoint blockade offers not only the abscopal effect to inhibit growth of distant tumors but also effective long‐term immune memory protection from rechallenged tumors. Therefore, such a light‐triggered in situ gelation system by a single‐dose injection can enable greatly enhanced photoimmunotherapy by means of repeated stimulations.     

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.     

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.     

Tumor‐Targeted Drug and CpG Delivery System for Phototherapy and Docetaxel‐Enhanced Immunotherapy with Polarization toward M1‐Type Macrophages on Triple Negative Breast Cancers

Cancer immunotherapy has achieved promising clinical responses in recent years owing to the potential of controlling metastatic disease. However, there is a limited research to prove the superior therapeutic efficacy of immunotherapy on breast cancer compared with melanoma and non‐small‐cell lung cancer because of its limited expression of PD‐L1, low infiltration of cytotoxic T lymphocytes (CTLs), and high level of myeloid‐derived suppressor cells (MDSCs). Herein, a multifunctional nanoplatform (FA‐CuS/DTX@PEI‐PpIX‐CpG nanocomposites, denoted as FA‐CD@PP‐CpG) for synergistic phototherapy (photodynamic therapy (PDT), photothermal therapy (PTT) included) and docetaxel (DTX)‐enhanced immunotherapy is successfully developed. The nanocomposites exhibit excellent PDT efficacy and photothermal conversion capability under 650 and 808 nm irradiation, respectively. More significantly, FA‐CD@PP‐CpG with no obvious side effects can remarkably inhibit the tumor growth in vivo based on a 4T1‐tumor‐bearing mice modal. A low dosage of loaded DTX in FA‐CD@PP‐CpG can promote infiltration of CTLs to improve efficacy of anti‐PD‐L1 antibody (aPD‐L1), suppress MDSCs, and effectively polarize MDSCs toward M1 phenotype to reduce tumor burden, further to enhance the antitumor efficacy. Taken together, FA‐CD@PP‐CpG nanocomposites offer an efficient synergistic therapeutic modality in docetaxel‐enhanced immunotherapy for clinical application of breast cancer.     

A Hollow‐Structured CuS@Cu2S@Au Nanohybrid: Synergistically Enhanced Photothermal Efficiency and Photoswitchable Targeting Effect for Cancer Theranostics

It is of great importance in drug delivery to fabricate multifunctional nanocarriers with intelligent targeting properties, for cancer diagnosis and therapy. Herein, hollow‐structured CuS@Cu₂S@Au nanoshell/satellite nanoparticles are designed and synthesized for enhanced photothermal therapy and photoswitchable targeting theranostics. The remarkably improved photothermal conversion efficiency of CuS@Cu₂S@Au under 808 nm near‐infrared (NIR) laser irradiation can be explained by the reduced bandgap and more circuit paths for electron transitions for CuS and Cu₂S modified with Au nanoparticles, as calculated by the Vienna ab initio simulation package, based on density functional theory. By modification of thermal‐isomerization RGD targeting molecules and thermally sensitive copolymer on the surface of nanoparticles, the transition of the shielded/unshielded mode of RGD (Arg‐Gly‐Asp) targeting molecules and shrinking of the thermally sensitive polymer by NIR photoactivation can realize a photoswitchable targeting effect. After loading an anticancer drug doxorubicin in the cavity of CuS@Cu₂S@Au, the antitumor therapy efficacy is greatly enhanced by combining chemo‐ and photothermal therapy. The reported nanohybrid can also act as a photoacoustic imaging agent and an NIR thermal imaging agent for real‐time imaging, which provides a versatile platform for multifunctional theranostics and stimuli‐responsive targeted 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.     

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.     

Programmable NIR‐II Photothermal‐Enhanced Starvation‐Primed Chemodynamic Therapy using Glucose Oxidase‐Functionalized Ancient Pigment Nanosheets

Chemodynamic therapy (CDT) has attracted considerable attention recently, but the poor reaction kinetics restrict its practical utility in clinic. Herein, glucose oxidase (GOx) functionalized ancient pigment nanosheets (SrCuSi₄O₁₀, SC) for programmable near‐infrared II (NIR‐II) photothermal‐enhanced starvation primed CDT is developed. The SC nanosheets (SC NSs) are readily exfoliated from SC bulk suspension in water and subsequently functionalized with GOx to form the nanocatalyst (denoted as SC@G NSs). Upon laser irradiation, the photothermal effect of SC NSs can enhance the catalytic activity of GOx for NIR‐II photothermal‐enhanced starvation therapy, which effectively eliminates intratumoral glucose and produces abundant hydrogen peroxide (H₂O₂). Importantly, the high photothermal‐conversion efficiency (46.3%) of SC@G NSs in second biological window permits photothermal therapy of deep‐seated tumors under the guidance of NIR‐II photoacoustic imaging. Moreover, the acidity amplification due to gluconic acid generation will in turn accelerate the degradation of SC NSs, facilitating the release of strontium (Sr) and copper (Cu) ions. Both the elevated H₂O₂ and the released ions will prime the Cu²⁺/Sr²⁺‐H₂O₂ reaction for enhanced CDT. Thus, a programmable NIR‐II photothermal‐enhanced starvation primed CDT is established to combat cancer with minimal side effects.     

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.     

Through Scalp and Skull NIR‐II Photothermal Therapy of Deep Orthotopic Brain Tumors with Precise Photoacoustic Imaging Guidance

Brain tumor is one of the most lethal cancers owing to the existence of blood–brain barrier and blood–brain tumor barrier as well as the lack of highly effective brain tumor treatment paradigms. Herein, cyclo(Arg‐Gly‐Asp‐D‐Phe‐Lys(mpa)) decorated biocompatible and photostable conjugated polymer nanoparticles with strong absorption in the second near‐infrared (NIR‐II) window are developed for precise photoacoustic imaging and spatiotemporal photothermal therapy of brain tumor through scalp and skull. Evidenced by the higher efficiency to penetrate scalp and skull for 1064 nm laser as compared to common 808 nm laser, NIR‐II brain‐tumor photothermal therapy is highly effective. In addition, via a real‐time photoacoustic imaging system, the nanoparticles assist clear pinpointing of glioma at a depth of almost 3 mm through scalp and skull with an ultrahigh signal‐to‐background ratio of 90. After spatiotemporal photothermal treatment, the tumor progression is effectively inhibited and the survival spans of mice are significantly extended. This study demonstrates that NIR‐II conjugated polymer nanoparticles are promising for precise imaging and treatment of brain tumors.     

Integration of IR‐808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR‐excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR‐808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)‐functionalized silica layer is developed for PDT agent. The two booster effectors (dye‐sensitization and core–shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS₂ nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS₂ nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.     

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.     

Engineering Gold Nanorod–Copper Sulfide Heterostructures with Enhanced Photothermal Conversion Efficiency and Photostability

Plasmonic gold nanorods (Au NRs)–copper sulfide heterostructures have recently attracted much attention owing to the synergistically enhanced photothermal properties. However, the facile synthesis and interface tailoring of Au NRs–copper sulfide heterostructures remain a formidable challenge. In this study, the rational design and synthesis of Au NRs–Cu₇S₄ heterostructures via a one‐pot hydrothermal process is reported. Specifically, core–shell and dumbbell‐like Au NRs–Cu₇S₄ heterostructures are obtained with well‐controlled interfaces by employing the Au NRs with different aspect ratios. Both core–shell and dumbbell‐like Au NRs–Cu₇S₄ have proven effective as photothermal therapy agents, which offer both high photothermal stability and significant photothermal conversion efficiency up to 62%. The finite‐difference time domain simulation results confirm the coupling effect that leads to the enhanced local field as well as the optical absorption at the heterostructure interface. Importantly, these Au NRs–Cu₇S₄ heterostructures can be compatibly used as an 808 nm laser‐driven photothermal therapy agents for the efficient photothermal therapy of cancer cells in vitro. This study will provide new insight into the design of other noble metal–semiconductor heterostructures for a broad range of applications utilizing surface plasmon resonance enhancement phenomena.     

Dual‐Peak Absorbing Semiconducting Copolymer Nanoparticles for First and Second Near‐Infrared Window Photothermal Therapy: A Comparative Study

Near‐infrared (NIR) light is widely used for noninvasive optical diagnosis and phototherapy. However, current research focuses on the first NIR window (NIR‐I, 650–950 nm), while the second NIR window (NIR‐II, 1000–1700 nm) is far less exploited. The development of the first organic photothermal nanoagent (SPN_I‐II) with dual‐peak absorption in both NIR windows and its utilization in photothermal therapy (PTT) are reported herein. Such a nanoagent comprises a semiconducting copolymer with two distinct segments that respectively and identically absorb NIR light at 808 and 1064 nm. With the photothermal conversion efficiency of 43.4% at 1064 nm generally higher than other inorganic nanomaterials, SPN_I‐II enables superior deep‐tissue heating at 1064 nm over that at 808 nm at their respective safety limits. Model deep‐tissue cancer PTT at a tissue depth of 5 mm validates the enhanced antitumor effect of SPN_I‐II when shifting laser irradiation from the NIR‐I to the NIR‐II window. The good biodistribution and facile synthesis of SPN_I‐II also allow it to be doped with an NIR dye for fluorescence‐imaging‐guided NIR‐II PTT through systemic administration. Thus, this study paves the way for the development of new polymeric nanomaterials to advance phototherapy.     

Multifunctional RbxWO3 Nanorods for Simultaneous Combined Chemo‐photothermal Therapy and Photoacoustic/CT Imaging

Light‐triggered drug delivery based on near‐infrared (NIR)‐mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light‐responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light‐absorber, Rb _x WO₃ (rubidium tungsten bronze, Rb‐TB) nanorods. With doxorubicin (DOX) payload, the DOX‐loaded Rb‐TB composite (Rb‐TB‐DOX) simultaneously provides a burst‐like drug release and intense heating effect upon 808‐nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb‐TB‐DOX to the MCF‐7 cancer cells. Most remarkably, Rb‐TB‐DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX‐resistant MCF‐7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo‐photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo‐photothermal therapy is also conducted and realized on pancreatic (Pance‐1) tumor‐bearing nude mice. Apart from its promise for cancer therapy, the as‐prepared Rb‐TB can also be employed as a new dual‐modal contrast agent for photoacoustic tomography and (PAT) X‐ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X‐ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb _x WO₃ nanorods for applications in cancer theranostics.     

Achieving High‐Performance Photothermal and Photodynamic Effects upon Combining D–A Structure and Nonplanar Conformation

Various organic nanoagents have been developed for photothermal therapy (PTT) and photodynamic therapy (PDT) under near‐infrared (NIR) irradiation. Among them, small molecule‐based nanoagents are very attractive due to their advantages of well‐defined chemical structures, high purity, good reproducibility, and easy processability. However, only a few small molecule‐based nanoagents have been developed for PDT under NIR irradiation. Moreover, the mechanism of PDT under NIR is still elusive. Herein, a semiconducting small molecule (BTA) with donor–acceptor–donor structure and twisted conformation is developed for PDT/PTT under NIR irradiation. A large π‐conjugated electron‐deficient unit is used as the core to couple with two electron‐donating units, ensuring the strong absorption under 808 nm. Moreover, the donor–acceptor structures and twisted conformation can reduce the energy gap between the singlet and triplet states (?E_ST) to afford effective intersystem crossing, beneficial for reactive oxygen species generation. The mechanism is probed by experimental and theoretical evidence. Moreover, the BTA nanoparticles exhibit excellent biocompatibility and PTT/PDT in vitro performance under NIR irradiation. This provides a strategy for designing highly efficient PDT/PTT molecular materials.     

Multifunctional Reduced Graphene Oxide Hydrogel as Drug Carrier for Localized and Synergic Photothermal/Photodynamics/Chemo Therapy

To combine localized drug release with multimodal therapy for malignant tumor, a composite hydrogel as an integrative drug delivery system was facilely prepared. The system contains spinach extract(SE),reduced graphene oxide(r GO) and gold nanocages(Au NCs). SE conduces to the formation of hydrogel,and also serves as a green material for improving the biocompatibility of hydrogel, and a natural photosensitizer for killing tumor cells under laser radiation(660 nm). Au NCs show obvious photothermy and can enhance the generation of cytotoxic singlet oxygen(1O2). The composite hydrogel shell on tumor cells exhibits several competitive advantages including enhanced antitumor effect by retaining the high concentration of drugs around cancer cell, excellent PDT/PTT compatibility as well as high loading and controllable release of fluorouracil(5-FU) for synergetic multimodal treatment. The survival rate of He La cells incubated with 5-FU loaded hydrogel under NIR radiation for 10 min sharply decreases to 1.2%, indicating remarkably improved antitumor effects. These results demonstrate that the hydrogel is an excellent delivery carrier for localizable, NIR-responsive and combined PTT/PDT/Chemo synergetic antitumor.