Strong Near-infrared Absorption Research Articles

PH-Activatable NIR Hemicyanine for Mitochondria-Targeted Cancer Phototheranostics.

Photodynamic therapy (PDT) has garnered significant attention for cancer treatment due to its noninvasive nature, reduced drug resistance, and spatiotemporal controllability. However, traditional photosensitizers (PSs) face limitations such as severe systemic phototoxicity and shallow tissue penetration, which hinder the widespread clinical application of PDT. Capitalizing on the strong near-infrared (NIR) absorption and ease of structural modification of hemicyanine, we have designed a pH-activatable NIR hemicyanine PS (LET-15). It is specifically activated in the acid tumor microenvironment, subsequently targeting mitochondria and generating cytotoxic singlet oxygen under 660 nm laser irradiation, which selectively destroys tumor tissues while minimizing damage to healthy tissues. Additionally, it offers activatable fluorescence (FL) imaging with a high signal-to-noise ratio, enabling FL imaging-assisted tumor photoeradication. This study provides valuable guidance for designing tumor-specifically activated NIR PSs for precision PDT.

Near-Infrared Light-Responsive Molybdenum Disulfide Nanosheets for Controlling the Release of Nimodipine as NIR-Drug Delivery System

Here, we present a photothermally triggered drug delivery nanosystem MoS2-NIMO-CHIT-SH, using the thiolated chitosan (CHIT-SH)-modified molybdenum disulfide (MoS2) nanosheets as near-infrared (NIR) photo-responsive carriers, loaded with the dihydropyridine calcium antagonist drug Nimodipine (NIMO). Although NIMO is used to treat stroke, migraine, Alzheimer’s disease, cerebrovascular spasms, and hypertension, this drug is poorly water-soluble, with low bioavailability and lack of selectivity. Thus, there is an urgent need for a novel approach to creating NIMO formulations that are safe, effective, and have better solubility and bioavailability. To overcome these problems, we develop a cationic biopolymer functionalized MoS2 nanosheets as a photothermal drug carrier system to facilitate the NIR light-induced release of NIMO drugs. MoS2 nanosheets (<150 nm) as NIMO drug carriers are prepared through simple exfoliation of their bulk phase and then functionalized with CHIT-SH biopolymer to increase their physiological stability and biocompatibility. According to the results, MoS2-NIMO-CHIT-SH nanocomposites show strong NIR absorbance, which makes them a promising candidate for photothermal therapy.

Synergistic photothermal and chemo-therapeutic platform utilizing Cu2-xSe/PDA/AIPH nanoparticles for targeted tumor eradication.

In this study, we developed an innovative Cu2-xSe/PDA/AIPH nanoparticle platform that combines photothermal therapy and chemotherapy for effective tumor treatment. The Cu2-xSe nanoparticles, known for their strong near-infrared (NIR) absorption, were encapsulated within a polydopamine (PDA) and 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) matrix. Upon NIR irradiation, the platform triggers localized heating and subsequent thermal decomposition of AIPH, releasing ROS to induce significant oxidative damage in tumor cells. In vitro and in vivo experiments demonstrated that Cu2-xSe/PDA/AIPH nanoparticles exhibit excellent biocompatibility, effective photothermal conversion, and potent anticancer efficacy. This multifunctional nanosystem offers a promising approach for enhancing tumor therapy by combining PTT with ROS-mediated chemotherapy.

Near-Infrared Photothermal Conversion by Isocorrole and Phlorin Derivatives.

Photothermal therapy is a promising strategy for treating tumors and bacterial infections by using light irradiation to locally heat tissues. Metalloisoporphyrinoid materials have been investigated for their use as singlet oxygen photosensitizers for photodynamic therapy but remain underexplored as photothermal agents. Recently, two metallophlorin and two metalloisocorrole materials were found to have strong near-infrared absorbance, with low photoluminescent quantum yields, suggesting high rates of nonradiative decay. Here we demonstrate that when encapsulated into aggregated organic nanoparticles (a-Odots), these materials show high photothermal conversion efficiencies between 67.3 ± 8.4 and 75.7 ± 4.1%. When considered alongside their ability to generate singlet oxygen, these materials may show promise as agents for dual photothermal and photodynamic therapy.

Effective One-for-All Phototheranostic Agent for Hypoxia-Tolerant NIR-II Fluorescent/PA Image-Guided Phototherapy.

Near-infrared (NIR)-triggered type-I photosensitizers are crucial to address the constraints of hypoxic tumor microenvironments in phototherapy; however, significant challenges remain. By selecting an electron-deficient unit, a matched energy gap in the upper-level state is instrumental in boosting the efficiency of intersystem crossing for the type-I electron transfer process. 2-Cyanothiazole, an electron acceptor, is covalently linked with N, N-diphenyl-4-(thiophen-2-yl)aniline to yield a multifunctional photosensitizer (TTNH) that exhibits intrinsic NIR absorbance and compatible T2 energy levels, facilitating both radiative and nonradiative transitions. The prepared nanoparticles (TTNH NPs) assembled from TTNH are activated by an 808nm laser and generated the O2•- for hypoxia-tolerant type-I photodynamic therapy under both normoxia and hypoxic conditions. TTNH NPs emitted NIR-II fluorescence with an impressive NIR-II fluorescence quantum yield of 2.08%. With a high photothermal conversion efficiency of 51.8% under 808nm laser stimulation, TTNH NPs exhibit photothermal therapy performance, accompanied by enhanced photoacoustic imaging capability owing to their strong NIR absorption. These characteristics make TTNH an effective NIR-wavelength-triggered phototheranostic agent that outperforms NIR-II fluorescence/photoacoustic dual-model imaging-guided type-I photodynamic therapy/photothermal therapy against hypoxic tumors. This results provide valuable insight for developing high-performance NIR-II-emissive superoxide radical phototheranostic agents.

Synergistic effects of Au nanoparticles in SiO2@Au@Polyaniline system for improved photothermal performance.

ASiO2@Au@Polyaniline (SiO2@Au@PAN) system has been successfully fabricated leveraging the synergistic effects of gold nanoparticles (AuNPs) to realize enhanced photothermal performance. The SiO2@Au@PAN exhibited strong near-infrared (NIR) absorbance, excellent photothermal conversion efficiency, good dispersibility, and outstanding photostability. The SiO2 nanospheres as the template provided numerous binding sites for coating of AuNPs. Subsequently, aniline was grafted onto SiO2 to form PAN, which further facilitated the growth of AuNPs. The high efficiency of electron transfer from PAN to AuNPs was utilized to enhance the photothermal performance, resulting in a photothermal conversion efficiency of 41.47%. Additionally, the effects of SiO2 with different sizes on the anchoring of AuNPs and the impact of aniline with varying concentrations on the morphology and photothermal properties of the materials were investigated. Finally, we verified the photothermal therapeutic(PTT) effect of SiO2@Au@PAN at cellular level, with results demonstrating effective destruction of cancer cells. This work may provide an approach for establishing a multi-component PTT platform based on the synergistic effects of AuNPs, holding significant potential for biomedical and biochemistry applications.

High-Performance Perovskite Photodetectors with Suppressed Dark Current Density via Small Molecule in Antisolvent Strategy.

Dark current density, a critical parameter in perovskite photodetectors (PPDs), largely depends on the quality of the perovskite film. Herein, we introduce a new small molecule in antisolvent strategy to enhance perovskite film quality during the crystallization of Cs0.05(FA0.95MA0.05)0.95Pb(I0.95Br0.05)3. COTIC-4Cl, an N-type narrow bandgap nonfullerene small molecule with specific functional group, could strongly bind to the uncoordinated Pb2+ in the perovskite with assistance of antisolvent, enabling rapid supersaturation of perovskite solution and form dense structures under low-temperature annealing. This strategy leads to the decreased nonradiative recombination and improved carrier transport efficiency in COTIC-4Cl-modified perovskites. The PPDs based on COTIC-4Cl-modified films exhibit a broad spectral response from 300 to 815 nm, an exceptionally low dark current density of 2.17 × 10-11 A cm-2, and enhanced detectivities of 1.84 × 1014and 3.09 × 1012 Jones at 0 and -0.5 V bias, respectively. Improved responsivity and detectivity at 650-780 nm result from strong near-infrared light absorption by COTIC-4Cl. These optimized PPDs are comparable to commercial silicon photodetectors, promising significant advancements in cost-effective photodetector technology.

Thermal Annealing for High Performance and Memory Behavior in n-Type Organic Electrochemical Transistors.

N-type organic mixed ionic electronic conductors (n-OMIECs) struggle to match the performance of p-type counterparts, particularly in bioelectronics' flagship device, the organic electrochemical transistor. Enhancing n-type transistor performance typically necessitates the synthesis of new materials. More sustainable post-synthetic treatments, known to improve organic devices in dry and oxygen-free conditions, are not applied to n-OMIECs. This study introduces thermal annealing to enhance n-OMIECs' electron mobility without sacrificing their ability to take up ionic charges. Annealing increases the crystallinity of p(gNDI-gT2), the first designed n-OMIEC, enhancing its transistor performance to compete with new-generation NDI-based materials. Annealing reduces passive and in operando electrolyte uptake without compromising the device threshold voltage, keeping the device power demand low. The microstructure obtained by annealing, combined with the film's strong near-infrared (NIR) absorption and reduced water swelling, enables the creation of a device that retains photocurrent generated upon frequency-dependent light training. This leads to a microscale, water-compatible memory device that emulates the learning process of biological neurons triggered by light. This simple device can be implemented in artificial neural networks and face recognition platforms and achieve vector-matrix multiplication when fabricated in an array form, showcasing the potential for innovative applications in bioelectronics.

Molecular design of ternary copolymers with high photothermal performance in the near-infrared window for effective treatment of gliomas in vivo.

Photothermal therapy (PTT) is a promising approach for treating glioblastoma multiforme (GBM) with minimal invasiveness and favorable outcomes. Conjugated polymers as photothermal agents offer stability, biocompatibility, and adjustable absorption capacity. However, existing polymers face limitations in achieving high photothermal conversion efficiency and strong absorbance in the near-infrared (NIR) region, posing a risk of damaging healthy tissues surrounding GBM during precise PTT. Herein, a molecular design strategy was developed to create a series of ternary copolymers by incorporating various π-conjugated molecules into both the main chain and side chain. Through this approach, PDTT-253, with rational molar contents of three units and a relatively minor twisted architecture between donors and π-bridges, demonstrated strong NIR absorbance and high PCE of 85.1 % at 808 nm. Furthermore, PDTT-253 nanoparticles exhibited exceptional photothermal stability, photostability, and prolonged storage validity period. In vitro studies revealed high biocompatibility and strong NIR photothermal killing efficacy of PDTT-253 NPs when incubated with U87 cells. Following the injection of PDTT-253 NPs into U87 glioma-bearing mice, a single 808 nm laser irradiation treatment resulted in the inhibition of glioma growth, with the ablated glioma being entirely detached from the surrounding normal tissue after PTT treatment, leading to a comprehensive cure. These results suggest that photostable and biocompatible ternary copolymer nanoparticles based on PDTT-253 show promise for PTT therapy in brain tumors through in situ injection and NIR irradiation. STATEMENT OF SIGNIFICANCE: A molecular design strategy was developed to create a series of ternary copolymers by incorporating various π-conjugated molecules into the conjugated skeleton. Through this approach, PDTT-253, with rational molar contents of three units and a relatively minor twisted architecture between donors and π-bridges, demonstrated enhanced near-infrared (NIR) absorbance and photothermal conversion efficiency of 85.1 % at 808 nm. Furthermore, PDTT-253 nanoparticles exhibited exceptional photothermal stability, high biocompatibility, and strong NIR photothermal killing efficacy against U87 cells. Following the injection of PDTT-253 NPs into U87 glioma-bearing mice, a single 808 nm laser irradiation treatment resulted in the inhibition of glioma growth, with the ablated glioma being entirely detached from the surrounding normal tissue after photothermal therapy treatment, leading to a comprehensive cure.

Dithienopyran-Based Narrow-Bandgap Donor Polymers: Unveiling the Potential for Semitransparent Organic Solar Cells with Enhanced NIR Absorption

Semitransparent organic solar cells (ST-OSCs) have recently received considerable attention in the field of photovoltaics owing to their great potential in applications such as building-integrated photovoltaics, self-powered greenhouses, and vehicle coatings. Because the near-infrared (NIR) region is an invisible region whose photon content is higher than that of the visible region, it is preferable to apply photoactive materials with narrow bandgaps in ST-OSCs. Tremendous efforts have been made to develop narrow-bandgap non-fullerene acceptors, however, donor polymers with NIR absorption ability for efficient ST-OSCs have rarely been reported. In this study, two novel narrow-bandgap donor polymers, PDTP-TBT and PDTTP-TBT, are designed and synthesized. Both polymers exhibit strong NIR absorption and high transmittance in the visible region, suggesting their potential for use in ST-OSCs. An opaque OSC with a PDTTP-TBT-based photoactive layer achieves a higher power conversion efficiency (PCE) of 8.87% than a PDTP-TBT-based OSC (PCE of 3.65%) due to its better charge transport characteristics. Furthermore, an ST-OSC using PDTTP-TBT-based blend film exhibits a PCE of 6.72%, average visible transmittance of 43.9%, and light utilization efficiency of 2.95%.

An Expeditious Synthesis of Near-Infrared-Absorbing Imide-Based Graphene Nanoribbons and Their Photothermal Properties.

Graphene nanoribbons (GNRs) with low band gap and strong near-infrared (NIR) absorption are potential candidates for optoelectronic and biomedical applications. In this context, imide-based GNRs are promising, but there are no rational design principles that yield these robust GNRs with strong NIR absorption. Here, we demonstrate a rational synthesis route to achieve NIR-absorbing imide-based robust GNRs by exploring the bay region of polyperylene (PP). Using the oxidative Diels-Alder reaction, we have successfully introduced mono and diimide functional groups on PP. After cyclodehydrogenation, the resultant GNRs, benzoperylene imide GNR (BPI-GNR) and coronene diimide GNR (CDI-GNR), show oscillatory edge geometry with strong NIR absorption (up to 1000 nm) and optical band gap of ~1.3 eV. Computational studies also indicate that imide substituents play an important role in fine-tuning the optoelectronic properties of GNRs. Moreover, these GNRs are solution-processable and can be made into thin films via spray coating. Owing to the strong NIR absorption and imide substitutions, BPI and CDI-GNRs show good photothermal conversion with excellent cyclic stability.

An Expeditious Synthesis of Near‐Infrared‐Absorbing Imide‐Based Graphene Nanoribbons and Their Photothermal Properties

Graphene nanoribbons (GNRs) with low band gap and strong near‐infrared (NIR) absorption are potential candidates for optoelectronic and biomedical applications. In this context, imide‐based GNRs are promising, but there are no rational design principles that yield these robust GNRs with strong NIR absorption. Here, we demonstrate a rational synthesis route to achieve NIR‐absorbing imide‐based robust GNRs by exploring the bay region of polyperylene (PP). Using the oxidative Diels‐Alder reaction, we have successfully introduced mono and diimide functional groups on PP. After cyclodehydrogenation, the resultant GNRs, benzoperylene imide GNR (BPI‐GNR) and coronene diimide GNR (CDI‐GNR), show oscillatory edge geometry with strong NIR absorption (up to 1000 nm) and optical band gap of ~1.3 eV. Computational studies also indicate that imide substituents play an important role in fine‐tuning the optoelectronic properties of GNRs. Moreover, these GNRs are solution‐processable and can be made into thin films via spray coating. Owing to the strong NIR absorption and imide substitutions, BPI and CDI‐GNRs show good photothermal conversion with excellent cyclic stability.

Structural Effect of N-7 Alkylation in 6-Chloropurine on Cu (II) Binding: Effect of Anions and Magnetic Studies.

This study investigates the anion-directed assembly of discrete copper (II) complexes. The ligands of choice are two N7-alkyl-purine-based neutral ligands. These ligands facilitate the exclusive coordination through the N3 and N9 positions, preventing polymeric chain formation. Perchlorate ions promoted the formation of discrete paddlewheel-like complexes with the general formula [Cu2(μ-Pur)4(CH3CN)2]4+, while chloride ions yielded chloride-bridged dimers of the form [Cu2(Pur)2(μ-Cl)2Cl2]. Copper-copper bond distances within these complexes ranged from 2.92 to 2.98 Å. Magnetic susceptibility measurement of chloride-bridged complexes exhibited antiferromagnetic coupling, whereas paddlewheel complexes displayed more complex alternating ferromagnetic and antiferromagnetic interactions. Chloride-bridged compounds exhibited strong near-infrared absorption.

Biodegradable ICG-Conjugated Germanium Nanoparticles for In Vivo Near-Infrared Dual-Modality Imaging and Photothermal Therapy.

Theranostics, by integrating diagnosis and therapy on a single platform, enables real-time monitoring of tumors during treatment. To improve the accuracy of tumor diagnosis, the fluorescence and photoacoustic imaging modalities can complement each other to achieve high resolution and a deep penetration depth. Despite the superior performance, the biodegradability of theranostic agents plays a critical role in enhancing nanoparticle excretion and reducing chronic toxicity, which is essential for clinical applications. Herein, we synthesize biocompatible and biodegradable indocyanine green (ICG)-conjugated germanium nanoparticles (GeNPs) and investigate their biodistributions in nude mice and 4T1 tumor models after intravenous injections using near-infrared (NIR) dual-modality fluorescence and photoacoustic imaging. The ICG-conjugated GeNPs have strong NIR absorption due to the NIR-absorbing ICG and Ge in combination, emit strong NIR fluorescence due to the multilayered ICG coatings, and exhibit very low in vitro and in vivo toxicity. After tail vein injections, the ICG-conjugated GeNPs mainly accumulate in the liver and spleen as well as the tumor with the help of the enhanced permeability and retention effect. The tumor's fluorescence signal is much stronger than that of the control group injected with pure ICG solution, as the GeNPs can function as biodegradable carriers for efficiently delivering the ICG molecules to the tumor. Lastly, the ICG-conjugated GeNPs accumulated in the tumor can also be utilized for photothermal treatment under NIR laser irradiation, after which the tumor volume almost diminishes after 14 days. The experimental findings in this work demonstrate that the ICG-conjugated GeNPs are promising theranostic agents with exceptional biodegradability for in vivo NIR dual-modality imaging and photothermal therapy.

Molecular Engineering of a Tumor-Targeting Thione-Derived Diketopyrrolopyrrole Photosensitizer to Attain NIR Excitation Over 850 nm for Efficient Dual Phototherapy.

Photosensitizers with near-infrared (NIR) excitation, especially above 800 nm which is highly desired for phototherapy, remain rare due to the fast nonradiative relaxation process induced by exciton-vibration coupling. Here, a diketopyrrolopyrrole-derived photosensitizer (DTPA-S) is developed via thionation of carbonyl groups within the diketopyrrolopyrrole skeleton, which results in a large bathochromic shift of 81 nm, endowing the photosensitizer with strong NIR absorption at 712 nm. DTPA-S is then introduced with a functional biomolecule (N3-PEG2000-RGD) via click reaction for the construction of integrin αvβ3 receptor-targeted nano-micelles (NanoDTPA-S/RGD), which endows the photosensitizer with a further superlarge absorption redshift of 138 nm, thus extending the absorption maxima to ≈850 nm. Remarkably, thiocarbonyl substitution increases the nonbonding characters in frontier molecular orbitals, which can effectively suppress the nonradiative vibrational relaxation process via reducing the reorganization energy, enabling efficient reactive oxygen species (ROS) generation under 880 nm excitation. Screened by in vitro and in vivo assays, NanoDTPA-S/RGD with high water solubility, excellent tumor-targeting ability, and photodynamic/photothermal therapy synergistic effect exhibits satisfactory phototherapeutic performance. Overall, this study demonstrates a new design of efficient NIR-triggered diketopyrrolopyrrole photosensitizer with facile installation of functional biomolecules for potential clinical applications.

A morphologically transformable hypoxia-induced radical anion for tumor-specific photothermal therapy

Tumor microenvironment activatable therapeutic agents and their effective tumor accumulation are significant for selective tumor treatment. Herein, we provide an unadulterated nanomaterial combining the above advantages. We synthesize a perylene diimide (PDI) molecule substituted by glutamic acid (Glu), which can self-assemble into small spherical nanoparticles (PDI-SG) in aqueous solution. PDI-SG can not only be transformed into nanofibers at low pH conditions but also be reduced to PDI radical anion (PDI·‒), which exhibits strong near-infrared absorption and excellent photothermal performance. More importantly, PDI-SG can also be reduced to PDI·‒ in hypoxic tumors to ablate the tumors and minimize the damage to normal tissues. The morphological transformation from small nanoparticles to nanofibers makes for better tumor accumulation and retention. This work sheds light on the design of tumor microenvironment activatable therapeutics with precise structures for high-performance tumor therapy.

Oxidation of Weakly Interacting Diradicals: An Approach for Strong and Tunable Near-Infrared-Absorbing Dyes Based on Small Chromophores.

Near-infrared (NIR)-absorbing dyes are valuable for various applications, such as bioimaging and electronic devices. This work introduces a novel approach for designing NIR dyes, oxidation of weakly coupled diradicals. Our approach features a weak exchange interaction in diradicals, which potentially leads to bonding/antibonding molecular orbitals with a small energy gap. We found that removing one of two singly occupied molecular orbital electrons of the diradicals results in an exceptionally narrow frontier orbital energy gap. We examined a series of Blatter radical dimers, and the most weakly coupled diradical prepared in this work (ΔEST ∼ 0.12 eV) with a molecular weight of 590 Da exhibited a strong NIR absorption band reaching 2200 nm upon one-electron oxidation. The optical band gaps of the radical cations strongly correlate to the exchange interaction in the precursor neutral species, offering prediction and fine-tuning of the optical band gap in the NIR region.

Light-Responsive conjugated polymer nanoparticles with Spatial-Controlled camptothecin release via π − π stacking for improved Combinatorial therapy of breast cancer

The treatment of breast cancer (BC) remains a significant challenge, exemplified by the limitations of chemotherapy due to its high side effects. Light-responsive drug delivery systems (DDS) offer a promising approach to spatially and temporally release drugs, minimizing chemotherapy side effects and enhancing efficacy. However, achieving precise delivery and site-specific drug release poses complex challenges. Here, We present a novel nano-system combining light-responsive photothermal therapy (PTT) with photothermal-responsive chemotherapy via π − π Stacking. Conjugated polymer nanoparticles (cRGD-PTer N25/CPT NPs) is designed for spatiotemporal targeted PTT/chemotherapy. Research shows that the strong near-infrared absorption of PTer N25 endows cRGD-PTer N25/CPT NPs with excellent photothermal capabilities(57.4 %) and near-infrared laser-triggered drug release performance. The cRGD-PTer N25/CPT NPs enhanced BC-specific cellular accumulation, prolonged blood circulation, exhibited good biocompatibility, and improved PTT and chemotherapy efficacy in BC cell lines and mouse models while reducing systemic toxicity. The photothermal effect triggered the on-demand release of camptothecin (CPT), producing therapeutic effects and downregulating heat shock protein 70 (HSP 70), reducing cancer cell thermoresistance, and enhancing combined treatment efficacy. Under spatial and temporal control, the tumor growth inhibition rate of the cRGD-PTer N25/CPT NPs group reached 93.6 %, nearly eradicating tumor presence, whereas the control group exhibited only partial inhibition. Minimal cardiotoxicity and metastatic side effects are not observed. This work presents a viable strategy for designing novel controlled-release drug systems to improve breast cancer treatment efficiency.

Cairo pentagon tessellated covalent organic frameworks with mcm topology for near-infrared phototherapy

Despite the prevalent of hexagonal, tetragonal, and triangular pore structures in two-dimensional covalent organic frameworks (2D COFs), the pentagonal pores remain conspicuously absent. We herein present the Cairo pentagonal tessellated COFs, achieved through precisely chosen geometry and metrics of the linkers, resulting in unprecedented mcm topology. In each pentagonal structure, porphyrin units create four uniform sides around 15.5 Å with 90° angles, while tetrabiphenyl unit establish a bottom edge about 11.6 Å with 120° angles, aligning precisely with the criteria of Cairo Pentagon. According to the narrow bandgap and strong near-infrared (NIR) absorbance, as-synthesized COFs exhibit the efficient singlet oxygen (1O2) generation and photothermal conversion, resulting in NIR photothermal combined photodynamic therapy to guide cancer cell apoptosis. Mechanistic studies reveal that the good 1O2 production capability upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. The implementation of pentagonal Cairo tessellations in this work provides a promising strategy for diversifying COFs with new topologies, along with multimodal NIR phototherapy.

H2O2-Activatable Liposomal Nanobomb Capable of Generating Hypoxia-Irrelevant Alkyl Radicals by Photo-Triggered Cascade Reaction for High-Performance Elimination of Biofilm Bacteria.

High H2O2 levels are widely present at the infection sites or in the biofilm microenvironment. Herein, hemin with peroxidase-like catalytic activity and its substrate, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), are simultaneously introduced into a liposomal nanoparticle containing thermosensitive 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI)-loaded bovine serum albumin (BAG), rationally constructing an H2O2-activatable liposomal nanobomb (Lipo@BHA) for combating biofilm-associated bacterial infections with high performance. In the presence of H2O2, hemin can catalyze the conversion of ABTS into its oxidized form (ABTS·+) with strong near-infrared (NIR) absorption, which produces photonic hyperpyrexia to cause the decomposition of AIBI into oxygen-independent alkyl radicals (·R) and nitrogen (N2) microbubbles. The former not only directly damage bacterial cells but also significantly accelerates the oxidization of ABTS to ABTS·+ for augmenting photothermal-triggered generation of ·R. Interestingly, the released N2 can induce transient cavitation to rupture lysosomal nanoparticle and improve the biofilm permeability, thereby enhancing the antibiofilm effect of Lipo@BHA. The proposed Lipo@BHA exhibits satisfactory multi-mode combination antibacterial properties. Through endogenous H2O2-activated cascade reaction, Lipo@BHA achieves remarkable hypoxia-irrelevant ·R therapy of biofilm-associated wound infections with low cytotoxicity and good in vivo biosafety. Therefore, this work presents a versatile H2O2-activatable cascade ·R generation strategy for biofilm-specific therapeutic applications.