Multimodal Imaging-guided Photothermal Therapy Research Articles

A mitochondria-targeted biocompatible photothermal nanoscale hydrogen-bonded organic framework for effective multimodal-imaging guided breast cancer therapy

Organic small-molecule photothermal agents (smPTAs) have been extensively studied for biomedical applications due to their good biocompatibility comparing with inorganic materials. However, most smPTAs suffer from water insolubility, even organic solvents insolubility, poor bio- and photo-stability, and short blood half-life. Herein, a new type of salinized 4,4′-(benzo[1,2-d:4,5-d']bis(thiazole)-2,6-diyl)dibenzoic acid (BBTDB-Na) smPTA is synthesized via a cyano group of 2-cyano-benzothiazole (CBT)-1,2-aminothiol group of cysteine (Cys) click condensation reaction, and photothermal nanoscale hydrogen-bonded organic frameworks (BT-nHOFs) is further constructed through a facile self-assembly strategy. The prepared BT-nHOFs exhibit a fusiform shape and bisthiazole structure, resulting in good cellular uptake and mitochondrial targeting effects. The well-organized structure of HOFs enables excellent photostability and high photothermal efficiency (51.4 %). Under 808 nm laser irradiation, the BT-nHOFs show favorable photothermal effects on breast cancer cells in vitro and in vivo, indicating that BT-nHOFs can act as a biocompatible PTA candidate for clinical applications. Besides, the fluorescence features, photoacoustic ability, cargo loading capacity of BT-nHOFs furnish multimodal imaging-guided precise photothermal therapy. In summary, this work paves a new way for the development of photothermal HOFs by salinizing insoluble smPTA and demonstrates their great potential for clinical application in phototheranostics.

An acid microenvironment-driven theranostics platform for lung cancer 19F MR/PA/FL multimodal imaging-guided photothermal therapy

Enhancing the tumor-to-background ratio in multimodal imaging to achieve precise tumor localization remains a pivotal objective for effective and specific photothermal therapy (PTT). However, developing tumor microenvironment-responsive multimodal probes for imaging-guided tumor therapy remains a formidable challenge. Herein, we engineered IR820-loaded fluorinated zeolitic imidazolate frameworks (ZIF-8) coated gold nanorod (GFZI) for FL/PA/19F MR trimodal-guided PTT in lung cancer. Upon reaching the tumor site, these nanoparticles trigger an enhancement in fluorescence imaging and 19F magnetic resonance imaging, facilitated by the controlled release of IR820 and 4-(trifluoromethyl)-1H-imidazole. Furthermore, GFZI undergoes degradation in the acidic tumor microenvironment, exposing the gold nanorods, thereby amplifying the photoacoustic signal and photothermal therapy. The amalgamation of acidic-activated FL/PA/19F MR trimodal imaging techniques ensures precise localization of lung cancer, realizing the outstanding PTT effect of lung cancer. This versatile platform holds great promise for achieving precision in cancer theranostics, offering new avenues in cancer diagnosis and treatment.

A noncovalent backbone planarization strategy increases the NIR-II extinction coefficients for gas/phototheranostic applications.

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

Hybrid FeWO4-Hyaluronic Acid Nanoparticles as a Targeted Nanotheranostic Agent for Multimodal Imaging-Guided Tumor Photothermal Therapy.

Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics. In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors. The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.

Versatile phototheranostic system: Aza-BODIPY-based nanoparticles with B,O-chelated core and diiodine

The heavy atom effect is widely recognized for its ability to enhance the photodynamic effect, but it also gives rise to concerns about fluorescence quenching and low photothermal conversion efficiency. In this study, we introduced iodine atoms into B,O-chelated aza-BODIPY and coated them with DSPE-PEG2000 to achieve high singlet oxygen quantum yields (64.9 %), while simultaneously maintaining excellent fluorescence emission (Φ = 0.94 %) and photothermal conversion capability (PCE = 33.8 %). The B,O-chelated aza-BODIPY derivative shows a remarkable synergistic and improved phototherapy therapeutic performance mainly by the innovative enhancement of the π-conjugated structure from the B,O-chelated structure and partial weakening of intermolecular π-π stacking from the steric hindrance of iodine atoms, which was validated through in vivo and in vitro tumor diagnosis and elimination experiments, utilizing state-of-the-art fluorescence imaging, photoacoustic imaging, and photothermal imaging for multimodal imaging-guided photodynamic therapy and photothermal therapy. This groundbreaking approach effectively overcomes the limitations of the traditional heavy atom effect, and presents a pioneering perspective on constructing a versatile phototheranostic system for precise and efficient tumor treatment. By effectively addressing the challenges posed by the heavy atom effect and maximizing the capabilities of the photosensitizer, we pave the way for more accurate and effective approaches in combating tumors.

Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650–900 nm) to NIR-II (900–1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal–organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

Programmable multistage small-molecule nano-photosensitizer for multimodal imaging-guided photothermal therapy.

Photothermal therapy has become a promising approach as precision medicine to allow spatial control of therapeutic effect only in the site of interest. However, the full potential of PTT has not been realized due to the lack of simple photosensitizers (PSs) that can overcome multistage biological barriers and improve theranostic efficiency. Here, we develop a small molecule-based PS to enhance tumor-specific PTT by programming multistage transport and activation properties in molecular architecture. This PS can self-assemble into stable nanoparticles that accumulate passively in tumor, and then actively internalize through ligand-mediated endocytosis. Subsequently, the programmable degradable linkers are selectively cleaved, enabling size shrinkage for better tumor penetration, binding albumin to enhance the near-infrared fluorescence for low-background imaging, and activating photothermal conversion for tumor suppression. The self-delivery process can be programmed, representing the first multistage small-molecule nano-photosensitizer that overcomes multiple biological barriers and improves the PTT index of tumor. STATEMENT OF SIGNIFICANCE: Photothermal therapy has become a promising approach as precision medicine, but has not been realized due to the lack of simple photosensitizers that can overcome multistage biological barriers and improve theranostic efficiency. In this contribution, we solve this dilemma by developing a small molecule-based photosensitizer by programming multistage transport and activation properties in molecular architecture, which could self-assemble into stable nanoparticles that accumulate passively in tumor, and actively internalized through ligand-mediated endocytosis. Subsequently, the programmable activation by ROS triggered size reduction for tumor penetration and minimized the phototoxicity to normal tissue. The activatable fluorescence and photothermal properties made the photosensitizer intrinsically suitable for multimodal imaging-guided PTT, providing a promising supramolecular nanomedicine towards tumor precise diagnosis and therapy.

A Two-Pronged Strategy for Enhanced Deep-Tumor Penetration and NIR-II Multimodal Imaging-Monitored Photothermal Therapy.

The second near-infrared (NIR-II)-induced photothermal therapy (PTT) has attracted a great deal of attention in recent years due to its non-invasiveness and because it uses less energy. However, the penetration of photothermal agents into solid tumors is seriously impeded by the dense-tumor extracellular matrix (ECM) containing cross-linked hyaluronic acid (HA), thereby compromising the ultimate therapeutic effects. Herein, acid-labile metal-organic frameworks were employed as nanocarriers to efficiently mineralize hyaluronidase (HAase) and encapsulate Ag2S nanodots by a one-pot approach under mild conditions. The obtained nanocomposites (AHZ NPs) maintained enzyme activity and changed in size to prolong blood circulation and complete delivery of the cargo to the tumor. Moreover, the released HAase could specifically break out the HA to loosen ECM and enable the Ag2S nanodots to breeze through the tumor matrix space and gain access to the deep tumor. Under near-infrared laser irradiation, the AHZ NPs displayed remarkable fluorescence, outstanding photoacoustic signals, and excellent photothermal properties in the whole tumor. This work offers a promising two-pronged strategy via a decrease in nanoparticle size and the degradation of dense ECM for NIR-II multimodal imaging-guided PTT of deep tumors.

Acceptor-donor-acceptor structured phototheranostics for near-infrared II fluorescent and photoacoustic imaging-guided photodynamic and photothermal synergistic therapy

Multi-modal imaging-guided synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) show great benefits in cancer treatment. The phototheranostics with near-infrared (NIR) absorption, high reactive oxygen species (ROS) generation and photothermal conversion efficiency is highly desirable. Here, we designed and synthesized an “acceptor-donor-acceptor” (A-D-A) structured molecule named IDCIC, with strong absorbance in the NIR region. We further prepared IDCIC into water-soluble nanoparticles (NPs) by wrapping with 1,2-distearoylsn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)-2000]-amine (DSPE-PEG2000-NH2). The obtained IDCIC NPs show an NIR absorption peak at 760 nm and an NIR-II fluorescence spectrum peak at ∼1000 nm with a fluorescent quantum yield of 1.2%, enabling them excellent photoacoustic and NIR-II fluorescent imaging capabilities. Moreover, IDCIC NPs could simultaneously generate singlet oxygen (with a quantum yield of 9.1%), hydroxyl radicals (·OH) and heat (with a photothermal conversion efficiency of 78.9%) under 808-nm laser irradiation. Based on the above-mentioned properties, IDCIC NPs were used for dual-modal imagingguided synergistic photodynamic/photothermal therapy of cancer.

MnCO3-mineralized polydopamine nanoparticles as an activatable theranostic agent for dual-modality imaging-guided photothermal therapy of cancers.

Background: Single imaging modality is still insufficient to evaluate the biological and anatomical structures of tumors with high accuracy and reliability. Generation of non-specific contrast, leading to a low target-to-background signal ratio, results in low imaging resolution and accuracy. Tumor environment-specific activatable multifunctional contrast agents need to maximize the contrast signals, representing a dual imaging-guided photothermal therapy (PTT) at target tumor sites.Methods: Cellular uptake, cytotoxicity assay, and in vitro photothermal conversion efficiency of MnCO3-mineralized fluorescent polydopamine nanoparticles (MnCO3-FPNPs) were evaluated using 4T1 breast cancer cells. In vivo dual-modality imaging was performed using IVIS imaging and a 4.7 T animal MRI systems after injection into 4T1 tumor-bearing nude mice. The effects of photothermal therapeutic through PTT were measured after irradiation with an 808 nm laser (1.5 W/cm2) for 10 min, measuring the size of the tumors every 2 days.Results: At physiological pH (7.4), MnCO3-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn2+ from the FPNPs. At pH 7.4, MnCO3-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO3 maintenance; conversely, at acidic pH (5.4), MnCO3-FPNPs efficiently release Mn2+ ions, thereby resulting in T1-weighted magnetic resonance (MR) contrast enhancement. MnCO3-FPNPs display a promising diagnostic ability for 4T1 breast cancer xenograft models, as well as exhibit a high photothermal conversion efficiency. A successful tumor treatment via their photothermal activity is accomplished within 14 days.Conclusions: Our studies exhibited unique “OFF-ON” activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO3-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.

A versatile nanoagent for multimodal imaging-guided photothermal and anti-inflammatory combination cancer therapy.

Photothermal therapy (PTT) has drawn great attention in cancer treatment because of its minimal invasiveness and high spatiotemporal selectivity, but it still encounters severe obstacles like heat-resistance, metastasis and recurrence. A key reason for the treatment failure is the highly inflammatory tumor microenvironment caused by hyperthermia. A simultaneous anti-inflammatory therapy alongside the PTT has great potential for overcoming the drawbacks of PTT; however, it has been less reported and further study is urgently needed. In addition, as many inorganic photothermal agents have no inherent imaging capability, diagnostic strategies should be introduced to help identify cancerous lesions and find the best treatment time period for PTT. Herein, we developed a versatile theranostic nanoagent (named T-lipos-CPAuNCs) for synergistic multimodal imaging-guided photothermal/anti-inflammatory cancer therapy. Perfluorohexane (PFH) loaded AuNCs and the anti-inflammatory drug celecoxib were encapsulated into the tumor-targeting cyclic Arg-Gly-Asp (cRGD) peptide modified liposomes to form T-lipos-CPAuNCs. The T-lipos-CPAuNCs accumulated in the tumor tissue and selectively targeted the cancer cells, and converted photo to thermal energy under near-infrared (NIR) laser irradiation to kill the cancer cells by PTT. The high temperature further accelerated the release of celecoxib to exert an anti-inflammatory effect, while on the other hand led to liquid to gas phase transition of PFH to facilitate ultrasound (US) imaging. The T-lipos-CPAuNCs also exhibited photoacoustic (PA) imaging capability. In vitro and in vivo experiments established that under the guidance of multimodal imaging, T-lipos-CPAuNCs significantly suppressed the tumor growth by PTT and prevented tumor metastasis with non-apparent tumor inflammation. The developed theranostic nanosystem (T-lipos-CPAuNCs) shows great potential for PA/US multimodal imaging guided photothermal/anti-inflammatory combination cancer therapy.

Near-infrared small molecule coupled with rigidness and flexibility for high-performance multimodal imaging-guided photodynamic and photothermal synergistic therapy.

Photodynamic therapy (PDT) synergized photothermal therapy (PTT) shows superior clinical application prospects than single PDT or PTT. On the other hand, multimodal imaging can delineate comprehensive information about the lesion site and thus help to improve therapy accuracy. However, integrating all these functions into one single molecule is challenging, let alone balancing and maximizing the efficacy of each function. Herein, a near-infrared (NIR) small molecule (ETTC) with an "acceptor-donor-acceptor" structure was designed and synthesized by coupling rigity and flexibility to simultaneously achieve NIR-II fluorescence imaging (NIR-II FLI), photoacoustic imaging, PTT and PDT. The efficacy of each functionality was well balanced and optimized (NIR-II quantum yield: 3.0%; reactive oxygen species generation: 3.2-fold higher than ICG; photothermal conversion efficiency: 52.8%), which may be attributed to the coupling of the rigid and flexible structures in ETTC to tactically manipulate the energy dissipation paths (non-radiative against radiative decay). As a proof-of-concept, under the effective guidance of local-tumor imaging by PA and whole-body imaging by NIR-II FL, complete tumor eradication was achieved via PDT and PTT combinational therapy. This work provides a novel perspective into conceiving and developing single molecule for efficient versatile biomedical applications.

A simple strategy for simultaneously enhancing photostability and mitochondrial-targeting stability of near-infrared fluorophores for multimodal imaging-guided photothermal therapy.

Near-infrared fluorophores are emerging as promising molecular tools for cancer theranostics because of their inherent biodegradability, low toxicity, and synthetic flexibility. However, they still suffer from several limitations, such as poor photostability and insufficient organelle-targeting stability during photothermal therapy. In this work, we introduce an "aldehyde functionalization" strategy for simultaneously enhancing photostability and mitochondria-immobilization of near-infrared fluorophores for the first time. Based on the proposed strategy, representative near-infrared organic molecules, namely AF-Cy, were rationally designed and synthesized. Upon aldehyde modification, the AF-Cy dyes displayed both remarkable photostability and mitochondrial-targeting stability. The strong absorption in the near-infrared region confers the AF-Cy dyes with outstanding fluorescent/photoacoustic imaging and photothermal therapy capabilities. Finally, in vitro and in vivo studies revealed the enhanced performance in inhibiting the growth of breast tumors under NIR laser radiation, and these results suggested the strong potential of AF-Cy dyes as efficient multimodal imaging-guided photothermal therapy agents, further highlighting the value of this simple strategy in the design high performance near-infrared fluorophores for tumor theranostics.

Lysosome-Targeted Gold Nanotheranostics for In Situ SERS Monitoring pH and Multimodal Imaging-Guided Phototherapy.

The integration of surface-enhanced Raman spectrum (SERS) and fluorescence-photoacoustic multimodal imaging in near-infrared photothermal therapy is highly desirable for cancer theranostic. However, typically, gold nanotheranostics usually require an additional modification of fluorophores and complex design refinements. In this work, by integrating surface-modified cysteine-hydroxyl merocyanine (CyHMC) molecules onto AuNRs, a novel lysosome-targeted gold-based nanotheranostics AuNRs-CyHMC that combines the specificity of Raman spectrum, the speed of fluorescence imaging, and deep penetration of photoacoustic imaging was successfully fabricated. Interestingly, fluorescence and Raman signals in this AuNRs-CyHMC system do not interfere, but it has pH-sensitive Raman signals and self-fluorescence localization ability under different excitation wavelengths. Fluorescence co-localization experiments further confirmed the lysosome-targeting ability of AuNRs-CyHMC. Typically, the proposed nanotheranostics were capable of SERS monitoring pH changes in both phosphate-buffered saline and living cells. Meanwhile, in vitro and in vivo experiments revealed that AuNRs-CyHMC possessed excellent fluorescence-photoacoustic performance and could be used for multimodal imaging-guided photothermal therapy. Furthermore, our work implied that gold nanotheranostics can provide great potential for cancer diagnosis and treatment.

Facile Synthesis of Melanin-Dye Nanoagent for NIR-II Fluorescence/Photoacoustic Imaging-Guided Photothermal Therapy.

BackgroundLaryngeal cancer is the second most common type of primary epithelial malignant tumor in the head and neck region, and the development of therapies that are more precise, efficient, and safe is necessary to preserve patient speech and swallowing functions as much as possible. Multi-modal imaging-guided photothermal therapy (PTT) can precisely delineate tumors, monitor the real-time accumulation of photothermal agents at the tumor site, accurately select the optimal region for irradiation, and predict the best time for laser treatment. Compared with exogeneous photothermal agents, endogenous melanin materials have better biosafety in vivo, in terms of native biocompatibility and biodegradability, as well as good near-infrared (NIR) absorbance. An NIR-II dye can be attached to melanin via a facile method, and applying a melanin-dye-based nanoprobe could be an excellent choice for the elimination of superficial laryngeal cancer while avoiding total laryngectomy.MethodsIn this work, a promising nanoprobe was constructed using a facile EDC/NHS strategy involving an NIR-II dye and melanin nanoparticles.ResultsThe nanoprobe exhibited good water solubility, dispersibility, strong NIR-II fluorescence and photoacoustic (PA) signals, and higher photothermal performance. Cellular studies showed that the nanoprobe had low toxicity, excellent biocompatibility, and significantly enhanced imaging properties. After the nanoprobe was intravenously injected into Hep-2 laryngeal xenografts, superior dual-modal images were obtained at various time points, which revealed that the optimal photothermal treatment time was 8 h. Subsequently, PTT was carried out in vivo, and laryngeal tumors were completely eliminated after laser irradiation without any obvious side effects.ConclusionThese results indicate the immense potential of nanoprobes for the NIR-II fluorescence/PA imaging-guided photothermal therapy of laryngeal cancer.

Hollow Porous Carbon Coated FeS2-Based Nanocatalysts for Multimodal Imaging-Guided Photothermal, Starvation, and Triple-Enhanced Chemodynamic Therapy of Cancer.

Specific chemical reactions only happen in the tumor region and produce abundant special chemicals to in situ trigger a train of biological and pathological effects that may enable tumor-specific curative effects to treat cancer without causing serious side effects on normal cells or organs. Chemodynamic therapy (CDT) is a rising tactic for cancer therapy, which induces cancer cell death via a localized Fenton reaction. However, the tumor therapeutic effect is limited by the efficiency of the chemical reaction and relies heavily on the catalyst. Here, we constructed hollow porous carbon coated FeS2 (HPFeS2@C)-based nanocatalysts for triple-enhanced CDT. Tannic acid was encapsulated in HPFeS2@C for reducing Fe3+ to Fe2+, which had a better catalytic activity to accelerate the Fenton reaction. Afterward, glucose oxidase (GOx) in nanocatalysts could consume glucose in the tumor microenvironment and in situ synchronously produce H2O2, which could improve Fenton reaction efficiency. Meanwhile, the consumption of glucose could lead to the starvation effect for cancer starvation therapy. The photothermal effects of HPFeS2@C could generate heat, which further sped up the Fenton process and implemented synergetic photothermal therapy/starvation therapy/CDT. The biodistribution of nanoparticles was investigated by multimodal magnetic resonance, ultrasound, and photoacoustic imaging. These nanocatalysts could trigger the catalytic Fenton reaction at a high degree, which might provide a good paradigm for nanocatalytic tumor therapy.

UCNP-Bi2 Se3 Upconverting Nanohybrid for Upconversion Luminescence and CT Imaging and Photothermal Therapy.

Non-invasive theranostics that integrate the advantages of multimodality imaging and therapeutics have great potential in the field of biomedicine. Herein, a new nanohybrid based on Bi2 Se3 -conjugated upconversion nanoparticles (UCNPs) has been successfully developed through a simple in situ growth strategy. Under 808 nm near-infrared laser irradiation, the UCNPs can emit bright visible light, whereas the Bi2 Se3 nanomaterial exhibits efficient photothermal conversion capacity. Moreover, the as-synthesized UCNP-Bi2 Se3 nanohybrid exhibits efficient cell upconversion luminescence (UCL), reasonable CT imaging, and admirable cancer cell ablation capacity, further emphasizing the efficiency of this strategy for simultaneous UCL imaging and photothermal therapy. The designed theranostic strategy guided by dual-modal imaging endowed with real-time dynamic monitoring, remote controllability, and non-invasiveness makes the UCNP-Bi2 Se3 nanohybrid an ideal candidate for non-invasive multimodal imaging-guided photothermal therapy for the precise diagnosis and treatment of cancer.

A novel αvβ3 integrin-targeted NIR-II nanoprobe for multimodal imaging-guided photothermal therapy of tumors in vivo.

Developing novel small-molecule-based probes with both deep tissue imaging and therapeutic functions is highly significant in cancer diagnosis and treatment. Herein, we report a novel second near-infrared (NIR-II) fluorescent probe QT-RGD constructed with a NIR-II emissive organic fluorophore and two cyclic-(arginine-glycine-aspartic acid) (cRGD) peptides that can specifically bind to the tumor-associated αvβ3 integrin for accurate tumor diagnosis and targeting therapy. The isotopic 125I-labeled probe exhibited great tumor targeting ability and emitted intensive NIR-II/photoacoustic (PA)/single-photon emission computed tomography (SPECT) signals, which allows specific and sensitive multimodal visualization of tumors in vivo. More notably, this probe could also be applied for effective imaging-guided photothermal therapy (PTT) of tumors in mouse models owing to its prominent photothermal conversion efficiency and excellent photothermal stability. We thus envision that our work which unveils a combination of NIR-II/PA/SPECT imaging and PTT would offer a valuable means of improving tumor diagnostic accuracy as well as therapeutic efficacy.

Coordination-induced exfoliation to monolayer Bi-anchored MnB2 nanosheets for multimodal imaging-guided photothermal therapy of cancer.

Background: Rapid advance in biomedicine has recently vitalized the development of multifunctional two-dimensional (2D) nanomaterials for cancer theranostics. However, it is still challenging to develop new strategy to produce new types of 2D nanomaterials with flexible structure and function for enhanced disease theranostics.Method: We explore the monolayer Bi-anchored manganese boride nanosheets (MBBN) as a new type of MBene (metal boride), and discover their unique near infrared (NIR)-photothermal and photoacoustic effects, X-ray absorption and MRI imaging properties, and develop them as a new nanotheranostic agent for multimodal imaging-guided photothermal therapy of cancer. A microwave-assisted chemical etching route was utilized to exfoliate the manganese boride bulk into the nanosheets-constructed flower-like manganese boride nanoparticle (MBN), and a coordination-induced exfoliation strategy was further developed to separate the MBN into the dispersive monolayer MBBN by the coordination between Bi and B on the surface, and the B-OH group on the surface of MBBN enabled facile surface modification with hyaluronic acid (HA) by the borate esterification reaction in favor of enhanced monodispersion and active tumor targeting.Result: The constructed MBBN displays superior NIR-photothermal conversion efficiency (η=59.4%) as well as high photothermal stability, and possesses versatile imaging functionality including photoacoustic, photothermal, CT and T1-wighted MRI imagings. In vitro and in vivo evaluations indicate that MBBN had high photothermal ablation and multimodal imaging performances, realizing high efficacy of imaging-guided cancer therapy.Conclusion: We have proposed new MBene concept and exfloliation strategy to impart the integration of structural modification and functional enhancement for cancer theranostics, which would open an avenue to facile fabrication and extended application of multifunctional 2D nanomaterials.

In situ decorating of ultrasmall Ag2Se on upconversion nanoparticles as novel nanotheranostic agent for multimodal imaging-guided cancer photothermal therapy

A novel multifunctional theranostic nanoplatform was fabricated via in situ growth of ultrasmall Ag2Se nanodots on the surface of chitosan (CS) coated NaYF4:Yb/Er@NaLuF4:Nd/Yb@NaLuF4 upconversion nanoparticles (UCNPs). NaYF4:Yb/Er@NaLuF4:Nd/Yb@NaLuF4@CS@Ag2Se (labeled as UCNPs@CS@Ag2Se) nanocomposites can provide downshifting (DS) and upconversion (UC) luminescence in NIR biological window I and II under 808-nm continuous-wave laser excitation simultaneously. Meanwhile, the attached Ag2Se nanodots could produce hyperthermia and photoacoustic energy upon 808-nm laser irradiation due to its strong near-infrared (NIR) absorbance. Together with the X-ray absorbance feature of lanthanide components, the nanocomposites with excellent luminescent properties, high X-ray attenuation coefficient and strong NIR absorbance could be utilized as a smart contrast agent for upconversion luminescence (UCL)/downshifting luminescence (DSL)/computer tomography (CT)/photoacoustic (PA) multimodal imaging in vitro and in vivo. Furthermore, the as-synthesized nanocomposites possess superior photothermal performance, good biocompatibility, and negligible toxicity, showing great potential as an ideal photothermal therapy (PTT) agent. These outstanding properties revealed that UCNPs@CS@Ag2Se nanocomposites are promising theranostic agents for tetra-modal imaging-guided PTT of cancer.