Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy.

Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond-laser ablation in liquids rapidly dissolve in physiological-like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half-life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near-infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9-fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass-extinction of Ge NPs (7.9 L g-1 cm-1 at 808 nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near-infrared-light biodegradable Ge nanomaterial holds promise for advanced theranostics.

A biodegradable semiconducting polymer phototherapeutic agent for safe cancer phototherapy.

Combined photodynamic therapy (PDT) and photothermal therapy (PTT) not only effectively reduce the hypoxic resistance to PDT, but also overcome the heat shock effect to PTT. However, the residual phototherapeutic agents still produce reactive oxygen species (ROS) to damage normal tissue under sunlight after treatment, which induces undesirable side effects to limit their biomedical application. Herein, a facile strategy is proposed to construct a biodegradable semiconducting polymer p-DTT, which is constructed by thieno[3,2-b]thiophene modified diketopyrrolopyrrole and (E)-1,2-bis(5-(trimethylstannyl)thiophen-2-yl)ethene moieties, to avoid the post-treatment side effects of phototherapy. Additionally, p-DTT exhibits strong photoacoustic (PA) for imaging, as well as good ROS production capacity and high photothermal conversion efficiency for synergistic PDT and PTT, which has been confirmed by both in vitro and in vivo results. After phototherapy, p-DTT could be gradually oxidized and degraded by endogenous ClO-, and subsequently lose ROS production and photothermal conversion capacities, which can guarantee the post-treatment safety, and address above key limitation of traditional phototherapy.

Recent advances in DNA-based probes for photoacoustic imaging.

Photoacoustic imaging(PAI) is a widely developing imaging modality that has seen tremendous evolvement in the last decade. PAI has gained the upper hand in the imaging field as it takes advantage of optical absorption and ultrasound detection that imparts higher resolution, rich contrast and elevated penetration depth. Unlike other imaging techniques, PAI does not use ionising radiation and is a better, cost-effective and healthier alternative to other imaging techniques. It offers greater specificity than conventional ultrasound imaging with the ability to detect haemoglobin, lipids, water and other light-absorbing chromophores. These properties of PAI have led to its extended applications in the biomedical field in the treatment of diseases such as cancer. This paper reviews how DNA probes have been used in PAI, the various techniques by which it has been modified, and their role in the process. We also focus on different nanocomposites containing DNA having PAI and photothermal therapy(PTT) properties for detection, diagnosis and therapy, its constituents and the role of DNA in it.

Theranostic Phthalocyanine and Naphthalocyanine Nanoparticles for Photoacoustic Imaging and Photothermal Therapy of Tumors.

Background: Phthalocyanine (PC) and naphthalocyanine (NC) dyes have long garnered interest as theranostic agents for optical imaging and phototherapy due to their near-infrared absorbance, photostability, imaging contrast, and proven safety in clinical trials. Yet, only a small fraction of these dyes has been evaluated as photothermal therapy (PTT) agents for cancer treatment. Methods: Nearly 40 distinct NC and PC dyes were encapsulated within polymeric PEG-PCL micelles via oil-in-water emulsions. The optimal NC/PC-loaded micelle formulations for PTT and photoacoustic (PA) imaging were identified through in vivo and in vitro studies. Results: The most promising candidate, CuNC(Octa)-loaded micelles, demonstrated a strong PA signal with a peak absorbance at ~870 nm, high photothermal efficiency, and photostability. The CuNC(Octa)-loaded micelles exhibited heat generation as good or better than gold nanorods/nanoshells and >10-fold higher photoacoustic signals. Micelle preparation was reproducible/scalable, and the CuNC(Octa)-loaded micelles are highly stable under physiological conditions. The CuNC(Octa)-loaded micelles localize within tumors via enhanced permeability and retention and are readily detectable by PA imaging. In a syngeneic murine tumor model of triple-negative breast cancer, CuNC(Octa)-loaded micelles demonstrate efficient heat generation with PTT, leading to the complete eradication of tumors. Conclusions: CuNC(Octa)-loaded micelles represent a promising theranostic agent for PA imaging and PTT. The ability to utilize conventional ultrasound in combination with PA imaging enables the simultaneous acquisition of information about tumor morphology and micelle accumulation. PTT with CuNC(Octa)-loaded micelles can lead to the complete eradication of highly invasive tumors.

Benzobisthiadiazole-Based Small Molecular Near-Infrared-II Fluorophores: From Molecular Engineering to Nanophototheranostics.

Organic fluorescent molecules with emission in the second near-infrared (NIR-II) biological window have aroused increasing investigation in cancer phototheranostics. Among these studies, Benzobisthiadiazole (BBT), with high electron affinity, is widely utilized as the electron acceptor in constructing donor-acceptor-donor (D-A-D) structured fluorophores with intensive near-infrared (NIR) absorption and NIR-II fluorescence. Until now, numerous BBT-based NIR-II dyes have been employed in tumor phototheranostics due to their exceptional structure tunability, biocompatibility, and photophysical properties. This review systematically overviews the research progress of BBT-based small molecular NIR-II dyes and focuses on molecule design and bioapplications. First, the molecular engineering strategies to fine-tune the photophysical properties in constructing the high-performance BBT-based NIR-II fluorophores are discussed in detail. Then, their biological applications in optical imaging and phototherapy are highlighted. Finally, the current challenges and future prospects of BBT-based NIR-II fluorescent dyes are also summarized. This review is believed to significantly promote the further progress of BBT-derived NIR-II fluorophores for cancer phototheranostics.

Photoacoustic Imaging Endometriosis Lesions with Nanoparticulate Polydopamine as a Contrast Agent.

Endometriosis (EM) is a prevalent and debilitating gynecological disorder primarily affecting women of reproductive age. The diagnosis of EM is historically hampered by delays, owing to the absence of reliable diagnostic and monitoring techniques. Herein, it is reported that photoacoustic imaging can be a noninvasive modality for deep-seated EM by employing a hyaluronic-acid-modified polydopamine (PDA@HA) nanoparticle as the contrast agent. The PDA@HA nanoparticles exhibit inherent absorption and photothermal effects when exposed to near-infrared light, proficiently converting thermal energy into sound waves. Leveraging the targeting properties of HA, distinct photoacoustic signals emanating from the periphery of orthotopic EM lesions are observed. These findings are corroborated through anatomical observations and in vivo experiments involving mice with green fluorescent protein-labeled EM lesions. Moreover, the changes in photoacoustic intensity over a 24 h period reflect the dynamic evolution of PDA@HA nanoparticle biodistribution. Through the utilization of a photoacoustic ultrasound modality, in vivo assessments of EM lesion volumes are conducted. This innovative approach not only facilitates real-time monitoring of the therapeutic kinetics of candidate drugs but also obviates the need for the sacrifice of experimental mice. As such, this study presents a promising avenue for enhancing the diagnosis and drug-screening processes of EM.

Hybrid Nanoparticle-Assisted Chemo-Photothermal Therapy and Photoacoustic Imaging in a Three-Dimensional Breast Cancer Cell Model.

Bioinspired nanoparticles have recently been gaining attention as promising multifunctional nanoplatforms for therapeutic applications in cancer, including breast cancer. Here, the efficiency of the chemo-photothermal and photoacoustic properties of hybrid albumin-modified nanoparticles (HSA-NPs) loaded with doxorubicin was evaluated in a three-dimensional breast cancer cell model. The HSA-NPs showed a higher uptake and deeper penetration into breast cancer spheroids than healthy breast cell 3D cultures. Confocal microscopy revealed that, in tumour spheroids incubated with doxorubicin-loaded NPs for 16 h, doxorubicin was mainly localised in the cytoplasm, while a strong signal was detectable at the nuclear level after 24 h, suggesting a time-dependent uptake. To evaluate the cytotoxicity of doxorubicin-loaded NPs, tumour spheroids were treated for up to 96 h with increasing concentrations of NPs, showing marked toxicity only at the highest concentration of doxorubicin. When doxorubicin administration was combined with laser photothermal irradiation, enhanced cytotoxicity was observed at lower concentrations and incubation times. Finally, the photoacoustic properties of doxorubicin-loaded NPs were evaluated in tumour spheroids, showing a detectable signal increasing with NP concentration. Overall, our data show that the combined effect of chemo-photothermal therapy results in a shorter exposure time to doxorubicin and a lower drug dose. Furthermore, owing to the photoacoustic properties of the NPs, this nanoplatform may represent a good candidate for theranostic applications.

Imaging-Guided Photoacoustic Immunotherapy Based on the Polydopamine-Functionalized Black Phosphorus Nanocomposites.

Phototherapy has great application prospects in superficial tumors, such as melanoma, esophageal cancer, and breast carcinoma, owing to the advantages of noninvasiveness, high spatiotemporal selectivity, and less side effects. However, classical phototherapies including photodynamic and photothermal therapy still need to settle the bottleneck problems of poor efficacy, inevitable thermal damage, and a high rate of postoperative recurrence. In this study, we developed a nanocomposite with excellent optical properties and immune-stimulating properties, termed PBP@CpG, which was obtained by functionalizing black phosphorus (BP) with polydopamine and further adsorbing CpG. Benefiting from the protection of polydopamine against BP, ideal light absorption, and photoacoustic conversion properties, PBP@CpG not only enables precisely delineation of the tumor region with photoacoustic imaging but also powerfully disrupts the plasma membrane and cytoskeleton of tumor cells with a photoacoustic cavitation effect. In addition, we found that the photoacoustic cavitation effect was also capable of inducing immunogenic cell death and remarkably strengthening the antitumor immune response upon cooperating with immune adjuvant CpG. Therefore, PBP@CpG was expected to provide a promising nanoplatform for optical theranostics and herald a new strategy of photoimmunotherapy based on the photoacoustic cavitation effects and immunostimulatory effect.

Glucose-responsive enzymatic biomimetic nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic anticancer therapy.

Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H2O2 at the tumor site. More importantly, the self-supplied peroxide hydrogen (H2O2) can convert ABTS (2,2'-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe2+ arising from the reduction of Fe3+ by overexpressed GSH reacts with H2O2 to generate intensely reactive •OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies. STATEMENT OF SIGNIFICANCE: Combinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H2O2. The self-supplied H2O2 initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous •OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy.

Asymmetric aza-BODIPY photosensitizer for photoacoustic/photothermal imaging-guided synergistic photodynamic/photothermal therapy.

Cancer synergistic therapy usually shows improved therapeutic efficacy with low side effects. In this contribution, an aza-BODIPY-derived photosensitizer NBDP with asymmetric structure and the periphery phenyl ring modified with bromine atom was designed and synthesized for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). Photosensitizer NBDP exhibited good singlet oxygen (1O2) generation capacity (1.43 times higher than that of ICG), and NBDP NPs showed an outstanding photothermal conversion efficiency (η) of 46.0% under 660 nm photoirradiation. Guided by in vivo photoacoustic (PA) imaging, NBDP NPs were found to targetedly accumulate in the tumor tissues in 6 h. All results showed that the aza-BODIPY-derived photosensitizer NBDP had great potential for PA/photothermal imaging-guided synergistic PTT/PDT.

In Situ Photoacoustic Visualization of Pneumonia Induced by MRSA and Specific Identifying Tumor-Homing Bacteria.

Optical imaging holds great promise for monitoring bacterial infectious processes and drug resistance with high temporal-spatial resolution. Currently, the diagnosis of deep-seated bacterial infections in vivo with fluorescence imaging, including near-infrared (NIR) fluorescence imaging technology, remains a significant challenge due to its limited tissue penetration depth. In this study, we developed a highly specific targeting probe, Cy7-Neo-NO2, by conjugating a bacterial 16S rRNA-targeted moiety, neomycin, with a bacterial nitroreductase (NTR)-activated NIR photoacoustic (PA) scaffold using our previously developed caged photoinduced electron transfer (a-PeT) approach. This conjugation effectively resolved probe aggregation issues in physiological conditions and substantially enhanced its reactivity toward bacterial NTR. Notably, Cy7-Neo-NO2 enabled the first in situ photoacoustic imaging of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA), as well as the detection of bacteria within tumors. Furthermore, upon NIR irradiation, Cy7-Neo-NO2 successfully inhibited MRSA growth through a synergistic effect combining photothermal therapy and photodynamic therapy. Our results provided an effective tool for obtaining exceptional PA agents for accurate diagnosis, therapeutic evaluation of deep-seated bacterial infections in vivo, and intratumoral bacteria-specific recognition.

Cobalt-doped hollow polydopamine for oxygen generation and GSH consumption enhanced chemo-PTT combined cancer therapy.

Nanotechnology has revolutionized the field of therapeutics by introducing a plethora of nanomaterials capable of enhancing traditional drug efficacy or paving the way for innovative treatment methods. Within this domain, we propose a novel Cobalt-doped hollow polydopamine nanosphere system. This system, incorporating Doxorubicin loading and hyaluronic acid (HA) surface coating (CoHPDA@DOX-HA), is designed for combined tumor therapy. The overarching aim is to diminish the administration dosage, mitigate the cytotoxic side effects of chemotherapy drugs, augment chemosensitivity within neoplastic tissues, and attain superior results in tumor treatment via combined therapeutic strategies. The targeted molecule, hyaluronic acid (HA), amplifies the biocompatibility of CoHPDA@DOX-HA throughout circulation and fosters endocytosis of the nanoparticle system within cancer cells. This nanosphere system possesses pH sensitivity properties, allowing for a meticulous drug release within the acidic microenvironment of tumor cells. Concurrently, Polydopamine (PDA) facilitates proficient photothermal therapy upon exposure to 808 nm laser irradiation. This process further amplifies the Glutathione (GSH) depletion, and when coupled with the oxygen production capabilities of the Cobalt-doped hollow PDA, significantly enhances the chemo-photothermal therapeutic efficiency. Findings from the treatment of tumor-bearing mice substantiate that even at dosages equivalent to a singular DOX administration, the CoHPDA@DOX-HA can provide efficacious synergistic therapy. Therefore, it is anticipated that multifunctional nanomaterials with Photoacoustic Tomography (PAT) imaging capabilities, targeted delivery, and a controlled collaborative therapeutic framework may serve as promising alternatives for accurate diagnostics and efficacious treatment strategies.

A manual controlled theranostic nanoplatform with real-time photoacoustic quantification of drug release for chemophotothermal therapy.

The development of intelligent nanodrug delivery systems that can visually guide the on-demand quantitative control of drug release has received extensive attention. Herein, two chemotherapeutic drugs, gallic acid and 5-fluorouracil, and Fe(III) were selected to prepare nanomedicine GF-Fe via polyphenol-metal self-assembly and infinite coordination of drug-metal. GF-Fe has good biocompatibility, photothermal properties and photoacoustic (PA) signals. When deferoxamine (DFO) was artificially applied and interacted with GF-Fe, GF-Fe began to disassemble, gallic acid and 5-fluorouracil were gradually released, while the PA signal of the nanomedicine decayed synchronously. Based on this, the relationship between the intensity of the PA signal and the drug release amount was established, so as to realize the precise quantitative control of the drug release in real-time under the guidance of PA imaging. Besides, the combined effect of the two therapeutic drugs in combination with photothermal therapy (PTT) can improve the therapeutic effect, resulting in significant superadditiveness. This nanoplatform constructed by facile synthesis provided good clinical translation potential for the implementation of precise multimodal combination therapy strategies for tumors.

Transcytosis-Inducing Multifunctional Albumin Nanomedicines with Deep Penetration Ability for Image-Guided Solid Tumor Treatment.

Transcytosis is an active transcellular transportation pathway that has garnered interest for overcoming the limited deep penetration of nanomedicines in solid tumors. In this study, a charge-convertible nanomedicine that facilitates deep penetration into solid tumors via transcytosis is designed. It is an albumin-based calcium phosphate nanomedicine loaded with IR820 (mAlb-820@CaP) for high-resolution photoacoustic imaging and enhanced photothermal therapy. Biomineralization on the surface stabilizes the albumin-IR820 complex during circulation and provides calcium ions (Ca2+ ) for tissue penetration on degradation in an acidic environment. pH-triggered transcytosis of the nanomedicine enabled by caveolae-mediated endocytosis and calcium ion-induced exocytosis in 2D cellular, 3D spheroid, and in vivo tumor models is demonstrated. Notably, the extravasation and penetration ability of the nanomedicine is observed in vivo using a high-resolution photoacoustic system, and nanomedicine shows the most potent photothermal antitumor effect in vivo. Overall, the strategy provides a versatile theragnosis platform for both noninvasive photoacoustic imaging and high therapeutic efficiency resulting from deep penetration of nanomedicine.

Space and Bond Synergistic Conjugation Controlling Multiple-Aniline NIR-II Absorption for Photoacoustic Imaging Guided Photothermal Therapy.

Currently, clinical photothermal therapy (PTT) is greatly limited by the poor tissue penetration of the excitation light sources in visible (390-780 nm) and first near-infrared (NIR-I, 780-900 nm) window. Herein, based on space and bond synergistic conjugation, a multiple-aniline organic small molecule (TPD), is synthesized for high-efficiency second near-infrared (NIR-II, 900-1700 nm) photoacoustic imaging guided PTT. With the heterogeneity of six nitrogen atoms in TPD, the lone electrons on the nitrogen atom and the π bond orbital on the benzene ring form multielectron conjugations with highly delocalized state, which endowed TPD with strong NIR-II absorption (maximum peak at 925 nm). Besides, according to the single molecular reorganization, the alkyl side chains on TPD make more free space for intramolecular motion to enhance the photothermal conversion ability. Forming TPD nanoparticles (NPs) in J-aggregation, they show a further bathochromic-shifted absorbance (maximum peak at 976 nm) as well as a high photothermal conversion efficiency (66.7%) under NIR-II laser irradiation. In vitro and in vivo experiments demonstrate that TPD NPs can effectively inhibit the growth of tumors without palpable side effects. The study provides a novel NIR-II multiple-aniline structure based on multielectron hyperconjugation, and opens a new design thought for photothermal agents.

Tumor microenvironment-mediated NIR-I-to-NIR-II transformation of Au self-assembly for theranostics.

The misdiagnosis of tumors due to insufficient penetration depth or signal interference and damage to normal tissues due to indiscriminate treatment are the biggest challenges in using photothermal agents for clinical translation. To overcome these limitations, a strategy of switching from the near-infrared (NIR)-I region to the NIR-II region was developed based on tumor microenvironment (TME)-mediated gold (Au) self-assembly. Using zeolitic imidazolate framework-8 (ZIF-8) metal-organic framework-coated gold nanorods (AuNRs@ZIF-8) as a model photothermal agent, we demonstrated that only a NIR-I photoacoustic imaging signal was observed in normal tissue because ZIF-8 could prevent the aggregation of AuNRs. However, when ZIF-8 dissociated in the TME, the AuNRs aggregated to activate NIR-II photoacoustic imaging and attenuate the NIR-I signal, thereby allowing an accurate diagnosis of tumors based on signal transformation. Notably, TME-activated NIR-II photothermal therapy could also inhibit tumor growth. Therefore, this TME-activated NIR-I-to-NIR-II switching strategy could improve the accuracy of deep-tumor diagnoses and avoid the injury caused by undifferentiated treatment. STATEMENT OF SIGNIFICANCE: Photothermal agents used for photoacoustic imaging and photothermal therapy have garnered great attention for tumor theranostics. However, always "turned on" near-infrared (NIR)-I laser (700-1000 nm)-responsive photothermal agents face issues of penetration depth and damage to normal tissues. In contrast, tumor microenvironment-activated NIR-II "smart" photothermal agents exhibit deeper penetration depth and tumor selectivity. Therefore, a NIR-I-to-NIR-II switching strategy was developed based on tumor microenvironment-mediated Au self-assembly. This work provides a new strategy for developing tumor microenvironment-activated NIR-II smart photothermal agents.

Bio-inspired self-assembled bacteriochlorin nanoparticles for superior visualization and photothermal ablation of tumors.

BACKGROUND: Although hyperthermia-based photothermal therapy (PTT) has achieved great success in the battle against malignant tumors, various commonly used photothermal sensitizers still suffer from non-selective tumor accumulation, limited photothermal conversion efficiency, potential toxicity and side effects, as well as complex and low cost-effective preparation process. Therefore, novel photothermal sensitizers are urgently required. The well-organized self-assembling of natural bacteriochlorophylls with superior photothermal property may provide an interesting option for the engineering of ideal PTS. METHODS: Inspired by the self-assembly peripheral light-harvesting antennas of natural bacteriochlorin in microorganisms, a biomimetic light-harvesting nanosystem (Nano-Bc) was developed via bacteriochlorophylls self-arranging in aqueous phase. The characterization of Nano-Bc were measured using DLS, TEM, UV-vis-near-infrared spectroscopy and preclinical PA imaging system. The cytotoxicity of Nano-Bc was quantitatively evaluated via a standard MTT assay using mouse breast cancer 4T1 cells, and the in vivo photothermal eradication of tumor was investigated in the 4T1 breast tumor-bearing mouse model. RESULTS: The obtained bacteriochlorin nanoparticles (Nano-Bc) exhibited ultra-high photothermal performance within the biological transparent window, showing superior heating capacity compared to commonly used photothermal sensitizers of organic dye indocyanine green and inorganic gold nanorods. Guiding by the inherent photoacoustic imaging of Nano-Bc, complete tumor elimination in vitro and vivo was evidenced upon laser irradiation. CONCLUSION: The green and facile preparation, ultra-high photothermal effect in the transparent window, excellent photoacoustic imaging capacity, and great biosafety prompt, the bio-inspired Nano-Bc as a promising theranostic platform against cancer in the areas of healthcare.

In situ-activated photothermal nanoplatform for on-demand NO gas delivery and enhanced colorectal cancer treatment.

The naturally evolved and intestinal pathogenic Fusobacterium nucleatum (Fn)-induced drug resistance profoundly impaired the efficacy of chemotherapy against colorectal cancer (CRC). Alternative treatment modalities against Fn-associated CRC are desperately needed. Herein, we engineer an in situ-activated anti-tumor and antibacterial nanoplatform (Cu2O/BNN6@MSN-Dex) to allow photoacoustic (PA) imaging-guided photothermal and NO gas combinatorial therapy for enhanced Fn-associated CRC treatment. The nanoplatform is constructed by loading cuprous oxide (Cu2O) and nitric oxide (NO) donor (BNN6) into dextran-decorated mesoporous silica nanoparticles (MSN), which is finally surface-functionalized with dextran via dynamic boronate linkage. Cu2O can be sulfuretted in situ by endogenous hydrogen sulfide overexpressed in CRC to produce copper sulfide with remarkable PA and photothermal properties, enabling the generation of NO from BNN6 under 808 nm laser irradiation, which is eventually triggered to release by multiple biological cues in the tumor microenvironment. Cu2O/BNN6@MSN-Dex exhibits superior biocompatibility, as well as H2S-triggered near-infrared-controlled antibacterial and anti-tumor performance in vitro and in vivo via photothermal and NO gas combination therapy. Furthermore, Cu2O/BNN6@MSN-Dex provokes systemic immune responses, thereby promoting anti-tumor efficacy. This study provides a conbinational strategy to effectively inhibit tumors and intratumor pathogens for enhanced CRC treatment.

Drug-Free Antimicrobial Nanomotor for Precise Treatment of Multidrug-Resistant Bacterial Infections.

Manufacturing heteronanostructures with specific physicochemical characteristics and tightly controllable designs is very appealing. Herein, we reported NIR-II light-driven dual plasmonic (AuNR-SiO2-Cu7S4) antimicrobial nanomotors with an intended Janus configuration through the overgrowth of copper-rich Cu7S4 nanocrystals at only one high-curvature site of Au nanorods (Au NRs). These nanomotors were applied for photoacoustic imaging (PAI)-guided synergistic photothermal and photocatalytic treatment of bacterial infections. Both the photothermal performance and photocatalytic activity of the nanomotors are dramatically improved owing to the strong plasmon coupling between Au NRs and the Cu7S4 component and enhanced energy transfer. The motion behavior of nanomotors promotes transdermal penetration and enhances the matter-bacteria interaction. More importantly, the directional navigation and synergistic antimicrobial activity of the nanomotors could be synchronously driven by NIR-II light. The marriage of active motion and enhanced antibacterial activity resulted in the expected good antibacterial effects in an abscess infection mouse model.