Tailoring near-infrared amyloid-ß probes with high-affinity and low background based on CN and amphipathic regulatory strategies and in vivo imaging of AD mice.

Amyloid-ß (Aß) species (Aß fibrils and Aß plaques), as one of the typical pathological markers of Alzheimer's disease (AD), plays a crucial role in AD diagnosis. Currently, some near-infrared I (NIR I) Aß probes have been reported in AD diagnosis. However, they still face challenges such as strong background interference and the lack of effective probe design. In this study, we propose molecular design strategy that incorporates CN group and amphiphilic modulation to synthesize a series of amphiphilic NIR I Aß probes, surpassing the commercial probe ThT and ThS. Theoretical calculations indicate that these probes exhibit stronger interaction with amino acid residues in the cavities of Aß. Notably, the probes containing CN group display the ability of binding two distinct sites of Aß, which dramatically enhanced the affinity to Aß species. Furthermore, these probes exhibit minimal fluorescence in aqueous solution and offer ultra-high signal-to-noise ratio (SNR) for in vitro labeling, even in wash-free samples. Finally, the optimal probe DM-V2CN-PYC3 was utilized for in vivo imaging of AD mice, demonstrating its rapid penetration through the blood-brain barrier and labelling to Aß species. Moreover, it enabled long-term monitoring for a duration of 120 min. These results highlight the enhanced affinity and superior performance of the designed NIR I Aß probe for AD diagnosis. The molecular design strategy of CN and amphiphilic modulation presents a promising avenue for the development Aß probes with low background in vivo/in vitro imaging for Aß species.

Highly sensitive near-infrared fluorescent probe for monitoring peroxynitrite in nonalcoholic fatty liver disease: Toward early diagnosis and therapeutic evaluation.

Nonalcoholic fatty liver disease (NAFLD) poses a significant global health concern, necessitating precise diagnostic tools and effective treatment strategies. Peroxynitrite (ONOO-), a reactive oxygen species, plays a pivotal role in NAFLD pathogenesis, highlighting its potential as a biomarker for disease diagnosis and therapeutic evaluation. This study reports on the development of a near-infrared (NIR) fluorescent probe, designated DRP-O, for the selective detection of ONOO- with high sensitivity and photostability. DRP-O exhibits rapid response kinetics (within 2 min) and an impressive detection limit of 2.3 nM, enabling real-time monitoring of ONOO- dynamics in living cells. Notably, DRP-O demonstrates excellent photostability under continuous laser irradiation, ensuring reliable long-term monitoring in complex biological systems. We apply DRP-O to visualize endogenous ONOO- in living cells, demonstrating its potential for diagnosing and monitoring NAFLD-related oxidative stress. Furthermore, DRP-O effectively evaluates the efficacy of therapeutic drugs in NAFLD cell models, underscoring its potential utility in drug screening studies. Moreover, we confirm DRP-O to enable selective identification of fatty liver tissues in a mouse model of NAFLD, indicating its potential for the early diagnosis of NAFLD. Collectively, DRP-O represents a valuable tool for studying ONOO- dynamics, evaluating drug efficacy, and diagnosing NAFLD, offering insights into novel therapeutic strategies for this prevalent liver disorder.

An intelligent NIR fluorescent dye with dual response to pH and viscosity for investigating the interactions between LDs and mitochondria.

The interaction between lipid droplets and mitochondria plays a pivotal role in biological processes including cellular stress, metabolic homeostasis, cellular autophagy and apoptosis. Deciphering the complex interplay between lipid droplets and mitochondria is essential for gaining insights into the fundamental workings of the cell and can have broad implications for the development of therapeutic strategies for various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. In this study, we develop a pH and viscosity-responsive near-infrared (NIR) fluorescent probe PTOH to investigate the interaction between lipid droplets and mitochondria. This probe demonstrates a significant enhancement in fluorescence intensity at 470 nm when the pH increases, while under acidic conditions, its fluorescence intensity at 730 nm intensifies by a factor of 35 with rising system viscosity. Cell imaging experiments revealed that PTOH can effectively discriminate between normal and cancerous cells, as well as detect intracellular pH and viscosity alterations induced by drugs. Additionally, PTOH is utilized to visualize the interaction between lipid droplets and mitochondria and to differentiate between cellular autophagy and apoptosis phenomena, providing a valuable tool for elucidating the mechanisms underlying lipid droplet-mitochondria interactions and their associated diseases.

Upconversion nanoparticles-CuMnO2 nanoassemblies for NIR-excited imaging of reactive oxygen species in vivo.

Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300-700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314-10 µM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.

Oxygen-defect bismuth oxychloride nanosheets for ultrasonic cavitation effect enhanced sonodynamic and second near-infrared photo-induced therapy of breast cancer.

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

NIR responsive scaffold with multistep shape memory and photothermal-chemodynamic properties for complex tissue defects repair and antibacterial therapy.

Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.

Rational construction of CQDs-based targeted multifunctional nanoplatform for synergistic chemo-photothermal tumor therapy.

Photothermal therapy combined with chemotherapy has shown great promise in the treatment of cancer. In this synergistic system, a safe, stable, and efficient photothermal agent is desired. Herein, an effective photothermal agent, carbon quantum dots (CQDs), was initially synthesized and then rationally constructed a folic acid (FA)-targeted photothermal multifunctional nanoplatform by encapsulating CQDs and the anticancer drug doxorubicin (DOX) in the liposomes. Indocyanine green (ICG), a near infrared (NIR) photothermal agent, approved by the U.S. Food and Drug Administration, was embedded in the bilayer membrane to further enhance the photothermal effects and facilitate the rapid cleavage of liposomes for drug release. Triggered by the NIR laser, this engineered photothermal multifunctional nanoplatform, not only exhibited an excellent performance with the photothermal conversion efficiency of up to 47.14%, but also achieved controlled release of the payloads. In vitro, and in vivo experiments demonstrated that the photothermal multifunctional nanoplatform had excellent biocompatibility, enhanced tumor-specific targeting, stimuli-responsive drug release, effective cancer cell killing and tumor suppression through multi-modal synergistic therapy. The successful construction of this NIR light-triggered targeted photothermal multifunctional nanoplatform will provide a promising strategy for the design and development of synergistic chemo-photothermal combination therapy and improve the therapeutic efficacy of cancer treatment.

d-arginine-functionalized carbon dots with enhanced near-infrared emission and prolonged metabolism time for tumor fluorescent-guided photothermal therapy.

Carbon dots (CDs) have garnered significant interest owing to their distinctive optical properties. However, their bioimaging and biomedical applications are limited by pronounced fluorescence (FL) quenching in aqueous media and low tumor accumulation efficacy associated with their ultra-small size. This study proposes a simple surface modification approach using functioning d-arginine on CDs (d-Arg@CDs) to improve their near-infrared (NIR) FL in aqueous solution and maintain their high photothermal conversion properties. Because of the low utilization rate of dextral amino acids in animals, modifying CDs with low molecular weight d-arginine did not increase particle size but extended the metabolism time in blood circulation, thereby leading to enhanced accumulation efficacy at tumor sites in the mice model. The enhanced tumor accumulation of d-Arg@CDs resulted in significantly superior tumor NIR FL imaging and photothermal therapy performance compared with pure CDs and l-arginine functionalized CDs. This dextral amino acid modification approach is expected to be an effective tool for enhancing the biomedical applications of CDs.

NIR responsive nanosystem based on upconversion nanoparticle-engineered bacteria for immune/photodynamic combined therapy with bacteria self-clearing capability.

Biological engineering bacteria hold great promise in tumor therapy due to their targeted delivery, tumor penetration, and tumor-specific activation capabilities. However, the use of live bacteria raises safety concerns, as they can potentially cause infections or adverse immune responses in patients. Additionally, most biological engineering bacteria are only responsive to blue light, which has limited penetration depth within biological tissues. To address these limitations, we have developed a nanoplatform that combines dual-emission upconversion nanoparticles (referred to as DDUCNPs), which can realize dual-wavelength emission under dual-wavelength excitation, with biological engineering bacteria for tumor treatment and the self-clearance of biological engineering bacteria after therapy in the near-infrared (NIR) window. This design allows us to utilize 980 nm light, which is converted to blue light by the DDUCNPs, to activate the bacteria and promote the controlled release of tumor necrosis factor-alpha (TNF-α) for precise tumor ablation. Subsequently, we employ 808 nm excitation to achieve light conversion into the red light, thereby activating photosensitizer molecules and generating singlet oxygen (ROS) for in vivo clearance of the bacteria involved in the treatment. Simultaneously, the generated ROS also undergoes photodynamic therapy (PDT) on the tumor to enhance the therapeutic effect. By combining these elements on a single platform, our system achieves the activation and self-clearance of biological engineering bacteria in the NIR window, effectively enabling tumor treatment. This approach overcomes the limitations of blue light penetration and addresses safety concerns associated with live bacteria, offering a promising strategy for precise and controlled tumor therapy.

Fe-doped biodegradable dendritic mesoporous silica nanoparticles for starvation therapy and photothermal-enhanced cascade catalysis in tumor therapy.

Combination therapies have attracted significant attention because they address the limitations of monotherapy while improving overall efficacy. In this study, we designed a novel nanoplatform, named GOx@Fe-DMSN@PDA (GFDP), by integrating Fe2+ into dendritic mesoporous silica nanoparticles (DMSN) and selecting glucose oxidase (GOx) as the model drug loaded into the DMSN pores. Additionally, we coated the surface of the DMSN with polydopamine (PDA) to confer pH/near infrared (NIR) light-responsive controlled-release behavior and photothermal therapy (PTT). The introduction of Fe2+ into the DMSN framework greatly improved biodegradability and enhanced the peroxidase (POD)-like activity of GFDP. In addition, GOx could consume glucose and generate hydrogen peroxide (H2O2) within tumor cells to facilitate starvation therapy and enhance cascade catalysis. The PDA coating provided the DMSN with an intelligent response release ability, promoting efficient photothermal conversion and achieving the PTT effect. Cellular tests showed that under NIR light irradiation, GFDP exhibited a synergistic effect of PTT-enhanced starvation therapy and cascade catalysis, with a half-maximal inhibitory concentration (IC50) of 2.89 µg/mL, which was significantly lower than that of GFDP without NIR light irradiation (18.29 µg/mL). The in vivo anti-tumor effect indicated that GFDP could effectively accumulate at the tumor site for thermal imaging and showed remarkable synergistic therapeutic effects. In summary, GFDP is a promising nanoplatform for multi-modal combination therapy that integrates starvation therapy, PTT, and cascade catalysis.

Mild near-infrared laser-triggered photo-immunotherapy potentiates immune checkpoint blockade via an all-in-one theranostic nanoplatform.

One of the primary challenges for immune checkpoint blockade (ICB)-based therapy is the limited infiltration of T lymphocytes (T cells) into tumors, often referred to as immunologically "cold" tumors. A promising strategy to enhance the anti-tumor efficacy of ICB is to increase antigen exposure, thereby enhancing T cell activation and converting "cold" tumors into "hot" ones. Herein, we present an innovative all-in-one therapeutic nanoplatform to realize local mild photothermal- and photodynamic-triggered antigen exposure, thereby improving the anti-tumor efficacy of ICB. This nanoplatform involves conjugating programmed death-ligand 1 antibody (aPD-L1) with gadolinium-doped near-infrared (NIR)-emitting carbon dots (aPD-L1@GdCDs), which displays negligible cytotoxicity in the absence of light. But under controlled NIR laser irradiation, the GdCDs produce combined photothermal and photodynamic effects. This not only results in tumor ablation but also induces immunogenic cell death (ICD), facilitating enhanced infiltration of CD8+ T cells in the tumor area. Importantly, the combination of aPD-L1 with photothermal and photodynamic therapies via aPD-L1@GdCDs significantly boosts CD8+ T cell infiltration, reduces tumor size, and improves anti-metastasis effects compared to either GdCDs-based phototherapy or aPD-L1 alone. In addition, the whole treatment process can be monitored by multi-modal fluorescence/photoacoustic/magnetic resonance imaging (FLI/PAI/MRI). Our study highlights a promising nanoplatform for cancer diagnosis and therapy, as well as paves the way to promote the efficacy of ICB therapy through mild photothermal- and photodynamic-triggered immunotherapy.

Pt/Pd dual-modified porphyrin metal-organic frameworks for NIR-II photothermal-enhanced photodynamic/catalytic therapy.

Photodynamic therapy (PDT) and catalytic therapy were promising treatment modes, but tumor hypoxia and poor catalytic activity severely limited their efficacies. Herein, using a porphyrin metal-organic framework (PCN-224) as nanocarrier, a platinum/palladium (Pt/Pd) dual-modified PCN-224 nanoprobe (PCN-224-Pt@Pd) with strong peroxidase (POD)/catalase (CAT)-like activities was developed, achieving photothermal-promoted PDT/catalytic therapy. Compared with single ultrasmall Pt modifying, CAT-like activity of Pt/Pd dual-modifying increased oxygen concentration from 6.24 to 9.35 mg/L, which improved singlet oxygen (1O2) yield from 63.8 % to 82.9 %. Moreover, POD-like activity of Pt/Pd dual-modifying significantly accelerated hydroxyl radicals (·OH) generation. Importantly, PCN-224-Pt@Pd possessed near-infrared II (NIR-II) photothermal effect with a high efficiency (55.6 %), which further promoted ·OH production. Under combined therapy of PCN-224-Pt@Pd, the cell survival rate greatly reduced to 5.8 %, and the tumors were cured, suggesting NIR-II photothermal-enhanced PDT/catalytic therapy.

Integration of single-atom photothermal catalysts with surface-localized high temperature in peroxymonosulfate-based Fenton-like systems for enhanced antibiotics degradation.

This study delves into integrating single-atom catalysts with photothermal effect in peroxymonosulfate (PMS)-based Fenton-like systems for enhanced pollutant degradation. A single-atom photothermal catalyst (Co/PMCNs) was designed using mesoporous carbon spheres as both a single-atom support and a photothermal material. Near-infrared (NIR) light was employed due to its superior thermal effect and penetration capacity in water. It was found that Co/PMCNs could generate surface-localized high temperatures for accelerating PMS activation and reducing energy gap of activation reactions, leading to improved degradation performance. Surface-localized high temperatures were demonstrated as key in distinguishing photothermal heating from external heat sources for PMS activation. Moreover, this system performed well across various operating conditions and water matrices, with Co/PMCNs showing promising recyclability. This study highlights the impact of surface-localized high temperatures on heterogeneous catalysis under NIR irradiation, and underscores the potential of integrating single-atom catalysts with photothermal effects into advanced oxidation processes for effective water pollution control.

Near-Infrared Driven Gold Nanoparticles-Decorated g-C3N4/SnS2 Heterostructure through Photodynamic and Photothermal Therapy for Cancer Treatment.

Background: Phototherapy based on photocatalytic semiconductor nanomaterials has received considerable attention for the cancer treatment. Nonetheless, intense efficacy for in vivo treatment is restricted by inadequate photocatalytic activity and visible light response. Methods: In this study, we designed a photocatalytic heterostructure using graphitic carbon nitride (g-C3N4) and tin disulfide (SnS2) to synthesize g-C3N4/SnS2 heterostructure through hydrothermal process. Furthermore, Au nanoparticles were decorated in situ deposition on the surface of the g-C3N4/SnS2 heterostructure to form g-C3N4/SnS2@Au nanoparticles. Results: The g-C3N4/SnS2@Au nanoparticles generated intense reactive oxygen species radicals under near-infrared (NIR) laser irradiation through photodynamic therapy (PDT) pathways (Type-I and Type-II). These nanoparticles exhibited enhanced photothermal therapy (PTT) efficacy with high photothermal conversion efficiency (41%) when subjected to 808 nm laser light, owing to the presence of Au nanoparticles. The in vitro studies have indicated that these nanoparticles can induce human liver carcinoma cancer cell (HepG2) apoptosis (approximately 80% cell death) through the synergistic therapeutic effects of PDT and PTT. The in vivo results demonstrated that these nanoparticles exhibited enhanced efficient antitumor effects based on the combined effects of PDT and PTT. Conclusion: The g-C3N4/SnS2@Au nanoparticles possessed enhanced photothermal properties and PDT effect, good biocompatibility and intense antitumor efficacy. Therefore, these nanoparticles could be considered promising candidates through synergistic PDT/PTT effects upon irradiation with NIR laser for cancer treatment.

Photobiomodulation using red and infrared spectrum light emitting-diode (LED) for the healing of diabetic foot ulcers: a controlled randomized clinical trial.

Assessing the responses to the application of photobiomodulation using red and infrared spectrum light-emitting diodes (LED) on diabetic foot ulcers. Diabetic volunteers, of both genders, aged between 30 and 65 years, with grade I or II ulcers, were randomized into the groups: red LED, infrared LED, LED associated, and control. Home-based interventions took place on a daily basis for 12 weeks. Assessments of sample characterization were performed on day 1 and 90, and the variables wound healing index, mean skin temperature, sensitivity and pain in the wound area were measured at the pre-intervention time on days 1, 30, 60 and 90, with subsequent follow-up 30 days after the end of treatment. For statistical analysis, the software SPSS, version 17.0, intention-to-treat analysis, data normality was tested, and the linear mixed effects model, with a significance level of 5%. Magnitudes of clinical effect by Cohen's d. At the pre vs post intervention time of 90 days, we found a large clinical effect of G-LED V (d=1.7) and G -LED IV (d=1.6) in relation to G-C, where these intervention groups showed a tendency for faster wound healing compared to G-C. We also observed small clinical effect of G-LED IV, which showed greater reduction in the area in relation to G-LED V (d=0.4) and G-LED A (d=0.3). Conclusion: The use of individually applied red and infrared LED phototherapy clinically tended to be more effective for the reduction of diabetic foot ulcer areas, and infrared LED was the most effective. Trial registration: NCT03250533 (clinicaltrials.gov).

Optimizing near infrared laser irradiation and photosensitizer accumulation period for indocyanine green-mediated photodynamic therapy in breast cancer xenografts: a focus on treatment and characterization.

Photodynamic therapy (PDT) is a promising cancer treatment approach. Indocyanine green (ICG) is a water-soluble tricarbocyanine dye with a peak absorption wavelength of around 800 nm and possesses the capacity to produce reactive oxygen species. FTIR spectroscopy is rarely used and offers insights into molecular changes in cancer studies. MCF-7 cells were injected into Nude mouse. Once the tumor had grown to a size of 3-4 mm, mice were randomized into the 12 PDT groups. After each mouse received 5 mg/kg of ICG, they were photo-irradiated with a diode laser emitting light at 809 nm, followed by waiting intervals of 0, 30, 60, and 90 min. Laser irradiation parameters were 150, 250, 500 mW/cm2 and irradiation duration was 1200s. The tumor size was measured every day for four days. The FTIR spectroscopy was used to perform spectral analysis on tumor tissue samples. Four distinct regions (3600-2800 cm-1, 1750-1550 cm-1, 1540-1450 cm-1, and 1700-1100 cm-1) were analyzed, and Hierarchical Cluster study was carried out. A decrease in tumor volume was observed with all PDT applications, except, increases in tumor volume was observed at 150mW 90-minute group. PDT administered after 90 min revealed variations in 150mW and 250mW laser powers in the 3600 cm-1-2800 cm-1 range. The 250mW and 500mW applications resulted in a considerable reduction in fibroadenoma and carcinoma tissues, according to an analysis comparing the A1695 / A1635 ratio. It is proposed that the ideal treatments for further investigation have a power output of 250 mW.

Research Progress of Deep-Red to Near-Infrared Electroluminescent Materials Based on Organic Cyclometallated Platinum(II) Complexes.

In recent years, the near-infrared (NIR) light-emitting materials have attracted increasing attention due to the broad application prospects in the fields of military industry, aerospace, lighting, display and wearable devices. As the transition metal complexes, platinum(II) complexes have been shown to emit luminescence efficiently in NIR organic light-emitting diodes because of the unique d8 electron structure. This structure ensures that the platinum(II) complex molecules exhibit a high planarity, variety of excited states, and strong intermolecular interactions. This review summarizes the research progress of deep red to NIR organic light-emitting materials based on platinum(II) complexes in recent years and provides a certain reference for the further design and synthesis of NIR platinum(II) complex luminescent materials with superior performance.

Spacer Twisting Strategy to Realize Ultrabright Near-Infrared II Polymer Nanoparticles for Fluorescence Imaging-Guided Tumor Phototheranostics.

Conjugated polymers are becoming popular near-infrared II (NIR-II) phototheranostic agents (PTAs) due to their numerous advantages, such as high photostability, large molar extinction coefficients, and excellent photothermal properties. However, the strong π-π interactions between the chains of the conjugated polymers resulted in their generally low NIR-II emission quantum yields (QY). Therefore, the synthesis of conjugated polymers with high QY is an interesting but challenging task. Herein, we proposed a spacer twisting strategy to realize ultrabright NIR-II polymer nanoparticles for fluorescence imaging-guided tumor phototheranostics. Theoretical calculations indicated that the polymer PY-IT has the largest dihedral angle between the largely π-conjugated skeleton and the spacer, which can effectively inhibit intermolecular π-π stacking, resulting in an improved QY as high as 16.5% in nanoparticles. In addition, PY-IT NPs can effectively perform NIR-II imaging and photothermal treatment of tumors. The work presents some valuable guides for achieving ultrabright NIR-II polymeric PTAs with high QY.

Morphology-Mediated Tumor Deep Penetration for Enhanced Near Infrared II Photothermal and Chemotherapy of Colorectal Cancer.

The low permeability and heterogeneous distribution of drugs (including nanomedicines) have limited their deep penetration into solid tumors. Herein we report the design of gold nanoparticles with virus-like spikes (AuNVs) to mimic viral shapes and facilitate tumor penetration. Mechanistic studies revealed that AuNVs mainly entered cells through macropinocytosis, then transported to the Golgi/endoplasmic reticulum system via Rab11-regulated pathway, and finally exocytosed through recycling endosomes, leading to high cellular uptake, effective transcytosis, and deep tumor penetration compared to gold nanospheres (AuNPs) and gold nanostars (AuNSs). The high tumor accumulation and deep tumor penetration of mitoxantrone (MTO) facilitated by AuNVs endowed effective chemophotothermal therapy when exposed to a near-infrared II laser, significantly reducing tumor sizes in a mouse model of colorectal cancer. This study reveals a potent mechanism of viral-like structures in tissue penetration and highlights their potential as effective drug delivery carriers.

Facilely Achieving Near-Infrared-II J-Aggregates through Molecular Bending on a Donor-Acceptor Fluorophore for High-Performance Tumor Phototheranostics.

Constructing J-aggregated organic dyes represents a promising strategy for obtaining biomedical second near-infrared (NIR-II) emissive materials, as they exhibit red-shifted spectroscopic properties upon assembly into nanoparticles (NPs) in aqueous environments. However, currently available NIR-II J-aggregates primarily rely on specific molecular backbones with intricate design strategies and are susceptible to fluorescence quenching during assembly. A facile approach for constructing bright NIR-II J-aggregates using prevalent donor-acceptor (D-A) molecules is still lacking. In this study, we present a facile method that transforms D-A molecules into J-aggregates by simply bending the molecule through introducing a methyl group, enabling high-performance NIR-II phototheranostics. The TAA-BT-CN molecule exhibits hypsochromic-shift absorption upon forming H-aggregated NPs, while the designed mTAA-BT-CN with a bent structure demonstrates a bathochromic shift of over 100 nm in absorption upon forming J-aggregated NPs, leading to much enhanced NIR-II emission beyond 1100 nm. With respect to its H-aggregated counterpart with the aggregation-caused quenching (ACQ) phenomenon, the J-aggregated mTAA-BT-CN NPs exhibit a 7-fold increase in NIR-II fluorescence owing to their aggregation-induced emission (AIE) property as well as efficient generation of heat and reactive oxygen species under 808 nm light excitation. Finally, the mTAA-BT-CN NPs are employed for whole-body blood vessel imaging using NIR-II technology as well as imaging-guided tumor phototherapies. This study will facilitate the flourishing advancement of J-aggregates based on prevalent D-A-type molecules.