Bright Aggregation‐Induced‐Emission Dots for Targeted Synergetic NIR‐II Fluorescence and NIR‐I Photoacoustic Imaging of Orthotopic Brain Tumors

Precise diagnostics are of significant importance to the optimal treatment outcomes of patients bearing brain tumors. NIR‐II fluorescence imaging holds great promise for brain‐tumor diagnostics with deep penetration and high sensitivity. This requires the development of organic NIR‐II fluorescent agents with high quantum yield (QY), which is difficult to achieve. Herein, the design and synthesis of a new NIR‐II fluorescent molecule with aggregation‐induced‐emission (AIE) characteristics is reported for orthotopic brain‐tumor imaging. Encapsulation of the molecule in a polymer matrix yields AIE dots showing a very high QY of 6.2% with a large absorptivity of 10.2 L g^?1 cm^?1 at 740 nm and an emission maximum near 1000 nm. Further decoration of the AIE dots with c‐RGD yields targeted AIE dots, which afford specific and selective tumor uptake, with a high signal/background ratio of 4.4 and resolution up to 38 µm. The large NIR absorptivity of the AIE dots facilitates NIR‐I photoacoustic imaging with intrinsically deeper penetration than NIR‐II fluorescence imaging and, more importantly, precise tumor‐depth detection through intact scalp and skull. This research demonstrates the promise of NIR‐II AIE molecules and their dots in dual NIR‐II fluorescence and NIR‐I photoacoustic imaging for precise brain cancer diagnostics.     

Metabolizable Ultrathin Bi2Se3 Nanosheets in Imaging‐Guided Photothermal Therapy

Poly(vinylpyrrolidone)‐encapsulated Bi₂Se₃ nanosheets with a thickness of 1.7 nm and diameter of 31.4 nm are prepared by a solution method. Possessing an extinction coefficient of 11.5 L g^?1 cm^?1 at 808 nm, the ultrathin Bi₂Se₃ nanosheets boast a high photothermal conversion efficiency of 34.6% and excellent photoacoustic performance. After systemic administration, the Bi₂Se₃ nanosheets with the proper size and surface properties accumulate passively in tumors enabling efficient photoacoustic imaging of the entire tumors to facilitate photothermal cancer therapy. In vivo biodistribution studies reveal that they are expelled from the body efficiently after 30 d. The ultrathin Bi₂Se₃ nanosheets have large clinical potential as metabolizable near‐infrared‐triggered theranostic agents.     

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.     

Single‐Photomolecular Nanotheranostics for Synergetic Near‐Infrared Fluorescence and Photoacoustic Imaging‐Guided Highly Effective Photothermal Ablation

Multi‐modality imaging‐guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single‐photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT‐S) into an amphiphilic lipid, water‐dispersible IT‐S nanoparticles (IT‐S NPs) are prepared. The obtained IT‐S NPs have a very simple construction and possess ultra‐stable near‐infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual‐modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT‐S NPs are successfully visualized by NIR FL/PA dual‐modal imaging. With the comprehensive in vivo imaging information provided by IT‐S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT‐S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.     

Precise Deciphering of Brain Vasculatures and Microscopic Tumors with Dual NIR‐II Fluorescence and Photoacoustic Imaging

Diagnostics of cerebrovascular structures and microscopic tumors with intact blood–brain barrier (BBB) significantly contributes to timely treatment of patients bearing neurological diseases. Dual NIR‐II fluorescence and photoacoustic imaging (PAI) is expected to offer powerful strength, including good spatiotemporal resolution, deep penetration, and large signal‐to‐background ratio (SBR) for precise brain diagnostics. Herein, biocompatible and photostable conjugated polymer nanoparticles (CP NPs) are reported for dual‐modality brain imaging in the NIR‐II window. Uniform CP NPs with a size of 50 nm are fabricated from microfluidics devices, which show an emission peak at 1156 nm with a large absorptivity of 35.2 L g^?1 cm^?1 at 1000 nm. The NIR‐II fluorescence imaging resolves hemodynamics and cerebral vasculatures with a spatial resolution of 23 µm at a depth of 600 µm. The NIR‐II PAI enables successful noninvasive mapping of deep microscopic brain tumors (<2 mm at a depth of 2.4 mm beneath dense skull and scalp) with an SBR of 7.2 after focused ultrasound‐induced BBB opening. This study demonstrates that CP NPs are promising contrast agents for brain diagnostics.     

Graphene Nanomesh Promises Extremely Efficient In Vivo Photothermal Therapy

Reduced graphene oxide nanomesh (rGONM), as one of the recent structures of graphene with a surprisingly strong near‐infrared (NIR) absorption, is used for achieving ultraefficient photothermal therapy. First, by using TiO₂ nanoparticles, graphene oxide nanoplatelets (GONPs) are transformed into GONMs through photocatalytic degradation. Then rGONMs functionalized by polyethylene glycol (PEG), arginine–glycine–aspartic acid (RGD)‐based peptide, and cyanine 7 (Cy7) are utilized for in vivo tumor targeting and fluorescence imaging of human glioblastoma U87MG tumors having α_νβ₃ integrin receptors, in mouse models. The rGONM‐PEG suspension (1 μg mL^?1) exhibits about 4.2‐ and 22.4‐fold higher NIR absorption at 808 nm than rGONP‐PEG and graphene oxide (GO) with lateral dimensions of ≈60 nm and ≈2 μm. In vivo fluorescence imaging demonstrates high selective tumor uptake of rGONM‐PEG‐Cy7‐RGD in mice bearing U87MG cells. The excellent NIR absorbance and tumor targeting of rGONM‐PEG‐Cy7‐RGD results in an ultraefficient photothermal therapy (100% tumor elimination 48 h after intravenous injection of an ultralow concentration (10 μg mL^?1) of rGONM‐PEG‐Cy7‐RGD followed by irradiation with an ultralow laser power (0.1 W cm^?2) for 7 min), whereas the corresponding rGO‐ and rGONP‐based composites do not present remarkable treatments under the same conditions. All the mice treated by rGONM‐PEG‐Cy7‐RGD survived over 100 days, whereas the mice treated by other usual rGO‐based composites were dead before 38 days. The results introduce rGONM as one of the most promising nanomaterials in developing highly desired ultraefficient photothermal therapy.     

Biocompatible Conjugated Polymer Nanoparticles for Efficient Photothermal Tumor Therapy

Conjugated polymers (CPs) with strong near‐infrared (NIR) absorption and high heat conversion efficiency have emerged as a new generation of photothermal therapy (PTT) agents for cancer therapy. An efficient strategy to design NIR absorbing CPs with good water dispersibility is essential to achieve excellent therapeutic effect. In this work, poly[9,9‐bis(4‐(2‐ethylhexyl)phenyl)fluorene‐alt‐co‐6,7‐bis(4‐(hexyloxy)phenyl)‐4,9‐di(thiophen‐2‐yl)‐thiadiazoloquinoxaline] (PFTTQ) is synthesized through the combination of donor–acceptor moieties by Suzuki polymerization. PFTTQ nanoparticles (NPs) are fabricated through a precipitation approach using 1,2‐distearoyl‐ sn ‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000] (DSPE‐PEG₂₀₀₀) as the encapsulation matrix. Due to the large NIR absorption coefficient (3.6 L g^‐1 cm^‐1), the temperature of PFTTQ NP suspension (0.5 mg/mL) could be rapidly increased to more than 50 °C upon continuous 808 nm laser irradiation (0.75 W/cm²) for 5 min. The PFTTQ NPs show good biocompatibility to both MDA‐MB‐231 cells and Hela cells at 400 μg/mL of NPs, while upon laser irradiation, effective cancer cell killing is observed at a NP concentration of 50 μg/mL. Moreover, PFTTQ NPs could efficiently ablate tumor in in vivo study using a Hela tumor mouse model. Considering the large amount of NIR absorbing CPs available, the general encapsulation strategy will enable the development of more efficient PTT agents for cancer or tumor therapy.     

Aggregation-Induced Emission Luminogens Married to 2D Black Phosphorus Nanosheets for Highly Efficient Multimodal Theranostics

Inspired by the respective advantages of aggregation-induced emission (AIE)-active photosensitizers and black phosphorus nanomaterials in cancer treatment, the facile construction of novel AIE photosensitizers married to 2D black phosphorus nanosheets and their application for multimodal theranostics are demonstrated. The developed nanomaterial simultaneously possesses distinctive properties and multiple functions including excellent stability, good biocompatibility, intensive fluorescence emission in the NIR region, high-performance reactive oxygen species generation, good photothermal conversion efficiency, outstanding cellular uptake, and effective accumulation at the tumor site. Both in vitro and in vivo evaluation show that the presented nanotheranostic system is an excellent candidate for NIR fluorescence–photothermal dual imaging-guided synergistic photodynamic–photothermal therapies. This study thus not only extends the applications scope of AIE and black phosphorus materials, but also offers useful insights into designing a new generation of cancer theranostic protocol for potential clinical applications.     

A High‐Sensitivity and Low‐Power Theranostic Nanosystem for Cell SERS Imaging and Selectively Photothermal Therapy Using Anti‐EGFR‐Conjugated Reduced Graphene Oxide/Mesoporous Silica/AuNPs Nanosheets

A high‐sensitivity and low‐power theranostic nanosystem that combines with synergistic photothermal therapy and surface‐enhanced Raman scattering (SERS) mapping is constructed by mesoporous silica self‐assembly on the reduced graphene oxide (rGO) nanosheets with nanogap‐aligned gold nanoparticles (AuNPs) encapsulated and arranged inside the nanochannels of the mesoporous silica layer. Rhodamine 6G (R6G) as a Raman reporter is then encapsulated into the nanochannels and anti‐epidermal growth factor receptor (EGFR) is conjugated on the nanocomposite surface, defined as anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G, where PEG is polyethylene glycol and CPSS is carbon porous silica nanosheets. SERS spectra results show that rGO@CPSS‐Au‐R6G enhances 5 × 10⁶ magnification of the Raman signals and thus can be applied in the noninvasive cell tracking. Furthermore, it displays high sensitivity (detection limits: 10^?8m R6G solution) due to the “hot spots” effects by the arrangements of AuNPs in the nanochannels of mesoporous silica. The highly selective targeting of overexpressing EGFR lung cancer cells (A549) is observed in the anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G, in contrast to normal cells (MRC‐5). High photothermal therapy efficiency with a low power density (0.5 W cm^?2) of near‐infrared laser can be achieved because of the synergistic effect by conjugated AuNPs and rGO nanosheets. These results demonstrate that the anti‐EGFR‐PEG‐rGO@CPSS‐Au‐R6G is an excellent new theranostic nanosystem with cell targeting, cell tracking, and photothermal therapy capabilities.     

Hybrid Nanoparticle Pyramids for Intracellular Dual MicroRNAs Biosensing and Bioimaging

This study strategically fabricates multifunctional nanopyramids to allow the ultrasensitive quantification of dual microRNAs (miR‐203^b and miR‐21) in living cells and their responsive bioimaging in vivo. The nanopyramids, composed of Au‐Cu₉S₅ nanoparticles (NPs), upconversion NPs (UCNPs), and Ag₂S NPs, emit two luminescent signals simultaneously with excitation at 808 nm, arising from the UCNPs at 541 nm in the visible region and from the Ag₂S NPs at 1227 nm in the second window of near‐infrared (NIR‐II) region. The upconversion luminescence has a linear relationship with miR‐203^b from 0.13 to 54.54 fmol per 10 µg_RNA and a limit of detection (LOD) of 0.09 fmol per 10 µg_RNA, whereas the Ag₂S NP luminescence has a linear relationship with miR‐21 from 0.37 to 43.56 fmol per 10 µg_RNA, with a LOD of 0.23 fmol per 10 µg_RNA. Significantly, this study demonstrates that the nanopyramids can be successfully used for miRs‐responsive bioimaging in a tumor‐bearing animal model. Furthermore, taking advantage of the photothermal capabilities of pyramids, the tumors can also be eliminated completely. These nanopyramids not only overcome the obstacles in the simultaneous detection of multiple miRs at the cellular level but also provide a cancer theranostic platform in vivo.     

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.     

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.     

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.     

Plasmonic Pt Superstructures with Boosted Near‐Infrared Absorption and Photothermal Conversion Efficiency in the Second Biowindow for Cancer Therapy

Photothermal therapy triggered by near‐infrared light in the second biowindow (NIR‐II) has attracted extensive interest owing to its deeper penetration depth of biological tissue, lower photon scattering, and higher maximum permissible exposure. In spite of noble metals showing great potential as the photothermal agents due to the tunable localized surface plasmon resonance, the biological applications of platinum are rarely explored. Herein, a monocomponent hollow Pt nanoframe (“Pt Spirals”), whose superstructure is assembled with three levels (3D frame, 2D layered shells, and 1D nanowires), is reported. Pt Spirals exhibit outstanding photothermal conversion efficiency (52.5%) and molar extinction coefficients (228.7 m² mol^?1) in NIR‐II, which are much higher than those of solid Pt cubes. Simulations indicate that the unique superstructure can be a significant cause for improving both adsorption and the photothermal effect simultaneously in NIR‐II. The excellent photothermal effect is achieved and subsequently verified in in vitro and in vivo experiments, along with superb heat‐resistance properties, excellent photostability, and a prominent effect on computed tomography (CT) imaging, demonstrating that Pt Spirals are promising as effective theranostic platforms for CT imaging‐guided photothermal therapy.     

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.     

High‐Resolution 3D NIR‐II Photoacoustic Imaging of Cerebral and Tumor Vasculatures Using Conjugated Polymer Nanoparticles as Contrast Agent

Exogenous contrast‐agent‐assisted NIR‐II optical‐resolution photoacoustic microscopy imaging (ORPAMI) holds promise to decipher wide‐field 3D biological structures with deep penetration, large signal‐to‐background ratio (SBR), and high maximum imaging depth to depth resolution ratio. Herein, NIR‐II conjugated polymer nanoparticle (CP NP) assisted ORPAMI is reported for pinpointing cerebral and tumor vasculatures. The CP NPs exhibit a large extinction coefficient of 48.1 L g^?1 at the absorption maximum of 1161 nm, with an ultrahigh PA sensitivity up to 2 µg mL^?1. 3D ORPAMI of wide‐field mice ear allows clear visualization of regular vasculatures with a resolution of 19.2 µm and an SBR of 29.3 dB at the maximal imaging depth of 539 µm. The margin of ear tumor composed of torsional dense vessels among surrounding normal regular vessels can be clearly delineated via 3D angiography. In addition, 3D whole‐cortex cerebral vasculatures with large imaging area (48 mm²), good resolution (25.4 µm), and high SBR (22.3 dB) at a depth up to 1001 µm are clearly resolved through the intact skull. These results are superior to the recently reported 3D NIR‐II fluorescence confocal vascular imaging, which opens up new opportunities for NIR‐II CP‐NP‐assisted ORPAMI in various biomedical applications.     

Fabrication of photoactive heterostructures based on quantum dots decorated with Au nanoparticles

Silica based multifunctional heterostructures, exhibiting near infrared (NIR) absorption (650–1200 nm) and luminescence in the visible region, represent innovative nanosystems useful for diagnostic or theranostic applications. Herein, colloidal synthetic procedures are applied to design a photoactive multifunctional nanosystem. Luminescent silica (SiO₂) coated quantum dots (QDs) have been used as versatile nanoplatforms to assemble on their surface gold (Au) seeds, further grown into Au spackled structures. The synthesized nanostructures combine the QD emission in the visible region, and, concomitantly, the distinctive NIR absorption of Au nanodomains. The possibility of having multiple QDs in a single heterostructure, the SiO₂ shell thickness, and the extent of Au deposition onto SiO₂ surface have been carefully controlled. The work shows that a single QD entrapped in 16 nm thick SiO₂ shell, coated with Au speckles, represents the most suitable geometry to preserve the QD emission in the visible region and to generate NIR absorption from metal NPs. The resulting architectures present a biomedical potential as an effective optical multimodal probes and as promising therapeutic agents due to the Au NP mediated photothermal effect.     

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.     

Synthesis of BSA‐Coated BiOI@Bi2S3 Semiconductor Heterojunction Nanoparticles and Their Applications for Radio/Photodynamic/Photothermal Synergistic Therapy of Tumor

Developing an effective theranostic nanoplatform remains a great challenge for cancer diagnosis and treatment. Here, BiOI@Bi₂S₃@BSA (bovine serum albumin) semiconductor heterojunction nanoparticles (SHNPs) for triple‐combination radio/photodynamic/photothermal cancer therapy and multimodal computed tomography/photoacoustic (CT/PA) bioimaging are reported. On the one hand, SHNPs possess strong X‐ray attenuation capability since they contain high‐Z elements, and thus they are anticipated to be a very competent candidate as radio‐sensitizing materials for radiotherapy enhancement. On the other hand, as a semiconductor, the as‐prepared SHNPs offer an extra approach for reactive oxygen species generation based on electron–hole pair under the irradiation of X‐ray through the photodynamic therapy process. This X‐ray excited photodynamic therapy obviously has better penetration depth in bio‐tissue. What's more, the SHNPs also possess well photothermal conversion efficiency for photothermal therapy, because Bi₂S₃ is a thin band semiconductor with strong near‐infrared absorption that can cause local overheat. In vivo tumor ablation studies show that synergistic radio/photodynamic/photothermal therapy achieves more significant therapeutic effect than any single treatment. In addition, with the strong X‐ray attenuation and high near‐infrared absorption, the as‐obtained SHNPs can also be applied as a multimodal contrast agent in CT/PA imaging.     

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.