Recurrent Inhibition Research Articles

A distinctive nanocomposite hydrogel integrated platform for the healing of wound after the resection of melanoma

During the surgical removal of melanoma, that the incompletely eradicated cancer cells enter the circulatory system with blood flow will lead to the risk of distant metastasis and then the recurrence of postoperative residual tumor, which will greatly reduce the cure rate. Additionally, microbial resistance makes the problem of infection more serious during the process of defect repair. Considering these problems, we developed a nanocomposite hydrogel (Gel/PF127) with excellent mechanical properties, hemostasis and broad-spectrum antibacterial activity. It was used for the dual release system based on micelles and hydrogel used for maintaining long-term release of paclitaxel (PTX) at the wound site after melanoma surgery, thereby killing residual tumor cells and repairing tissue defects better. The results showed that PF127 nano micelles could effectively load PTX and release it in tumor environment. Moreover, the quaternary ammonium gel network showed excellent growth inhibition for E. coli and S. aureus (inhibition rate up to 98%). The introduction of Ca2+ endowed the gel with the excellent hemostatic effect. The combination of reversible chemical bonds and electrostatic interaction made Gel/PF127 have good mechanical stability, excellent tissue adhesion and self-healing properties. The experimental results showed that such nanocomposite hydrogel could stop bleeding quickly and avoid wound infection, induce apoptosis of tumor cells and inhibit their recurrence very effectively, thus suggesting that the construction of in situ chemotherapy platform which integrates trauma repair and tumor inhibition will greatly promote the recurrence inhibition and trauma repair of melanoma. At the same time, it provides a simple and efficient strategy for other cancer postoperative wound healing.

Amyotrophic lateral sclerosis weakens spinal recurrent inhibition and post-activation depression

ObjectivesAmyotrophic lateral sclerosis (ALS) disrupts motoneurons that control movement and some vital functions, however, exact details of the neuronal circuits involved in ALS have yet to be fully endorsed. To contribute to our understanding of the responsible neuronal circuits, we aimed to investigate the spinal recurrent inhibition (RI) and post-activation depression (P-AD) in ALS patients. MethodsIn two groups of ALS patients, i.e. lumbar-affected (clinical signs in leg muscles) and nonlumbar-affected (clinical signs in arms or bulbar region but not in the legs), RI and P-AD on the soleus muscle were investigated using single motor units and amplitude changes of H-reflex in surface electromyography, respectively. The data were compared with healthy subjects. ResultsCompared to controls, P-AD of H-reflex was reduced severely in lumbar-affected patients and reduced to a certain degree in nonlumbar-affected patients. Similarly, a significant reduction in the duration of RI on firing motoneurons was found in lumbar-affected patients (11.5 ± 2.6 ms) but not in nonlumbar-affected patients (29.7 ± 12.4 ms, P < 0.0001) compared to controls (30.8 ± 7.2 ms, P < 0.0001). ConclusionThe current study revealed that spinal inhibitory circuits are impaired in ALS. SignificanceThese findings may provide insight for proposing new therapeutic approaches and following disease progression in humans.

Activity of Various Essential Oils Against Clinical Dermatophytes of Microsporum and Trichophyton.

Dermatophytoses account for nearly a quarter of all fungal infections worldwide. These difficult to treat infections of the skin, hair, and nails, are growing more resistant to conventional antifungal treatments, and when treatable, often require prolonged therapeutic regimens. For centuries, essential oils have been used to treat a variety of ailments. In this study, we evaluated the clinical effects in vitro of 65 essential oils and 21 essential oil blends against various clinical species/strains of dermatophytes from two primary genera, Microsporum and Trichophyton. Our aim: To determine the overall activity of a wide range of essential oils against a number of clinical strains of dermatophytes. For all assays, 16 clinically derived species/strains of dermatophytes were used. The activity of each essential oil was assessed using a modified disk-diffusion assay over a period of 21 days of incubation vs. standard antifungal drugs. Subsequently, we determined the minimum inhibitory dilution possible for the most potent essential oils and performed combination testing to determine if synergy could be demonstrated with sub-inhibitory concentrations. We also assessed the effect of repeated vs. single applications. Of all the essential oils tested, cassia, cilantro, cinnamon, thyme, and oregano were the most potent along with one blend, DDR Prime; all genera/species tested were completely inhibited for 21 days following a single application. Many of the other oils tested exhibited temporal differences in activity where significant inhibition was observed ≤10 days of incubation which declined by day 21. Synergistic combinations were achieved with oregano and cilantro, cassia, or cinnamon bark; rose and cassia were also synergistic. Repeat application maintained complete inhibition for citronella, lemon myrtle, and litsea out to 21 days, but not lemon grass or On Guard. More study is necessary to understand the ways essential oils inhibit the growth of dermatophytes. Comprehensive research aimed at understanding the mechanism of action of essential oils and their components may provide the basis for a natural alternative to topical antifungal drugs. Such research could be envisioned to target optimal combinations and determine the timing between applications to provide for maximum inhibition of recurrence or growth.

Dendritic integration in olfactory bulb granule cells upon simultaneous multispine activation: Low thresholds for nonlocal spiking activity.

The inhibitory axonless olfactory bulb granule cells form reciprocal dendrodendritic synapses with mitral and tufted cells via large spines, mediating recurrent and lateral inhibition. As a case in point for dendritic transmitter release, rat granule cell dendrites are highly excitable, featuring local Na+ spine spikes and global Ca2+- and Na+-spikes. To investigate the transition from local to global signaling, we performed holographic, simultaneous 2-photon uncaging of glutamate at up to 12 granule cell spines, along with whole-cell recording and dendritic 2-photon Ca2+ imaging in acute juvenile rat brain slices. Coactivation of less than 10 reciprocal spines was sufficient to generate diverse regenerative signals that included regional dendritic Ca2+-spikes and dendritic Na+-spikes (D-spikes). Global Na+-spikes could be triggered in one third of granule cells. Individual spines and dendritic segments sensed the respective signal transitions as increments in Ca2+ entry. Dendritic integration as monitored by the somatic membrane potential was mostly linear until a threshold number of spines was activated, at which often D-spikes along with supralinear summation set in. As to the mechanisms supporting active integration, NMDA receptors (NMDARs) strongly contributed to all aspects of supralinearity, followed by dendritic voltage-gated Na+- and Ca2+-channels, whereas local Na+ spine spikes, as well as morphological variables, barely mattered. Because of the low numbers of coactive spines required to trigger dendritic Ca2+ signals and thus possibly lateral release of GABA onto mitral and tufted cells, we predict that thresholds for granule cell-mediated bulbar lateral inhibition are low. Moreover, D-spikes could provide a plausible substrate for granule cell-mediated gamma oscillations.

In vitro evaluation of composite containing DMAHDM and calcium phosphate nanoparticles on recurrent caries inhibition at bovine enamel-restoration margins

ObjectiveRecurrent caries is a primary reason for restoration failure caused by biofilm acids. The objectives of this study were to: (1) develop a novel multifunctional composite with antibacterial function and calcium (Ca) and phosphate (P) ion release, and (2) investigate the effects on enamel demineralization and hardness at the margins under biofilms. MethodsDimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP) were incorporated into composite. Four groups were tested: (1) Commercial control (Heliomolar), (2) Experimental control (0% DMAHDM + 0% NACP), (3) antibacterial group (3% DMAHDM + 0% NACP), (D) antibacterial and remineralizing group (3% DMAHDM + 30% NACP). Mechanical properties and Ca and P ion release were measured. Colony-forming units (CFU), lactic acid and polysaccharide of Streptococcus mutans (S. mutans) biofilms were evaluated. Demineralization of bovine enamel with restorations was induced via S. mutans, and enamel hardness was measured. Data were analyzed via one-way and two-way analyses of variance and Tukey’s multiple comparison tests. ResultsAdding DMAHDM and NACP into composite did not compromise the mechanical properties (P > 0.05). Ca and P ion release of 3% DMAHDM + 30% NACP was increased at cariogenic low pH. Biofilm lactic acid and polysaccharides were greatly decreased via DMAHDM, and CFU was reduced by 4 logs (P < 0.05). Under biofilm acids, enamel hardness at the margins was decreased to about 0.5 GPa for control; it was about 1 GPa for antibacterial group, and 1.3 GPa for antibacterial and remineralizing group (P < 0.05). ConclusionsThe novel 3% DMAHDM + 30% NACP composite had strong antibacterial effects. It substantially reduced enamel demineralization adjacent to restorations under biofilm acid attacks, yielding enamel hardness that was 2-fold greater than that of control composites. The novel multifunctional composite is promising to inhibit recurrent caries.

Abstract 6247: Drug delivery with real time customizable micro-scaled continuous liquid interface printed 3D devices

Abstract Background: Surgery is a key treatment for cancer. However, local recurrence after surgery is common and can lead to significant morbidity and mortality. Current strategies to prevent recurrence include intraoperative radiation or systemic chemotherapy. We hypothesize that local chemotherapy delivery can prevent recurrence while reducing toxicity. To accomplish this, we propose to engineer 3D printed devices that can deliver chemotherapy in a localized and prolonged fashion. Methods: Paclitaxel and a cisplatin prodrug were dissolved into a liquid resin mixture of PEG550-DMA and HEMA. Custom 3D patches were printed on a Carbon 3D continuous liquid interface printer with microneedles protruding from one side of a flat surface substrate. A non-drug loaded flat backing was also printed from the same resin, and adhered to back side of the microneedle patch. Tumor growth recurrence inhibition post surgical resection was assessed in NU/NU mice in both 344SQ/Luc and A431 tumor models. Tumors were inoculated subcutaneously (106 344SQ/Luc, 5 × 105 A431) and allowed to grow until they reached 5-7mm in length. Tumors were then surgically resected and mice were either given an IV drug treatment, or had a 3D printed patch implanted in the surgical pocket. Tumor recurrence was evaluated with both luciferase bioluminescence imaging and physical measurement of tumor size. Toxicity parameters were analyzed with enzyme and CBC tests. Results: All drug loaded patches showed significant tumor growth inhibition compared to their corresponding IV drug treatment groups. While single drug loaded patches were significant in their inhibition of tumor growth compared to IV delivery of the same drug, dual drug loaded patches showed the most significant tumor inhibition compared to either single IV drug treatment or a dual IV drug treatment. There were no significant differences in measured toxicity parameters between groups. Conclusions: Our data demonstrated that local drug delivery through a customizable 3D continuous liquid interface printed drug loaded patch can improve tumor growth recurrence inhibition post surgical resection. Citation Format: C. Tilden Hagan, Cameron J. Bloomquist, Joseph M. DeSimone, Andrew Z. Wang. Drug delivery with real time customizable micro-scaled continuous liquid interface printed 3D devices [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6247.

In vivo odorant input induces distinct synaptic plasticity of GABAergic synapses in developing zebrafish olfactory bulb

In the first station of central odor processing, the main olfactory bulb, signal processing is regulated by synaptic interactions between glutamatergic and GABAergic inputs of the mitral cells (MCs), the major projection neurons. Our previous study has found that repetitive postsynaptic spiking within a critical time window after presynaptic activation by natural odorant stimulation results in persistent enhancement of glutamatergic inputs of MCs in larval zebrafish. Here we observed a long-term depression of GABAergic synapses induced by the same protocol. This long-term depression was mediated by presynaptic NMDA receptors (NMDARs). Further dissecting GABAergic neurotransmission revealed that the STDP-induction protocol induced persistent modification in recurrent and lateral inhibition with opposite directions and distinct requirements on NMDARs. Thus, at the plasticity level, different types of GABAergic inhibition may utilize different mechanisms to cooperate or compete with excitatory inputs to optimize patterns of olfactory bulb output.

Supramolecular Tubustecan Hydrogel as Chemotherapeutic Carrier to Improve Tumor Penetration and Local Treatment Efficacy.

Local chemotherapy is a clinically proven strategy in treating malignant brain tumors. Its benefits, however, are largely limited by the rapid release and clearance of therapeutic agents and the inability to penetrate through tumor tissues. We report here on a supramolecular tubustecan (TT) hydrogel as both a therapeutic and drug carrier that enables long-term, sustained drug release and improved tumor tissue penetration. Covalent linkage of a tissue penetrating cyclic peptide to two camptothecin drug units creates a TT prodrug amphiphile that can associate into tubular supramolecular polymers and subsequently form a well-defined sphere-shaped hydrogel after injection into tumor tissues. The hollow nature of the resultant tubular assemblies allows for encapsulation of doxorubicin or curcumin for combination therapy. Our in vitro and in vivo studies reveal that these dual drug-bearing supramolecular hydrogels enhance tumor retention and penetration, serving as a local therapeutic depot for potent tumor regression, inhibition of tumor metastasis and recurrence, and mitigation of the off-target side effects.

Navigating 2D Monoelemental Materials (Xenes) for Cancer Nanomedicine

Contributing to this issue of Matter, Wei Tao, Tian Xie, and colleagues now demonstrate the killing of two birds (inhibition of tumor recurrence and wound infection) with one stone (germanene-based surgical adjuvant theranostic materials): another breakthrough of two-dimensional monoelemental materials (2D Xenes) as cancer nanomedicine.

Sparse coding with a somato-dendritic rule

Cortical neurons are silent most of the time: sparse activity enables low-energy computation in the brain, and promises to do the same in neuromorphic hardware. Beyond power efficiency, sparse codes have favourable properties for associative learning, as they can store more information than local codes but are easier to read out than dense codes. Auto-encoders with a sparse constraint can learn sparse codes, and so can single-layer networks that combine recurrent inhibition with unsupervised Hebbian learning. But the latter usually require fast homeostatic plasticity, which could lead to catastrophic forgetting in embodied agents that learn continuously. Here we set out to explore whether plasticity at recurrent inhibitory synapses could take up that role instead, regulating both the population sparseness and the firing rates of individual neurons. We put the idea to the test in a network that employs compartmentalised inputs to solve the task: rate-based dendritic compartments integrate the feedforward input, while spiking integrate-and-fire somas compete through recurrent inhibition. A somato-dendritic learning rule allows somatic inhibition to modulate nonlinear Hebbian learning in the dendrites. Trained on MNIST digits and natural images, the network discovers independent components that form a sparse encoding of the input and support linear decoding. These findings confirm that intrinsic homeostatic plasticity is not strictly required for regulating sparseness: inhibitory synaptic plasticity can have the same effect. Our work illustrates the usefulness of compartmentalised inputs, and makes the case for moving beyond point neuron models in artificial spiking neural networks.

Neural excitability of lower extremity musculature in individuals with and without chronic ankle instability: A systematic review and meta-analysis

This systematic review and meta-analysis examined differences in lower extremity neural excitability between ankles with and without chronic ankle instability (CAI). We searched the literature for studies that compared corticomotor or spinal reflexive excitability between a CAI group and controls or copers, or between limbs of a CAI group. Random effects meta-analyses calculated pooled effect sizes for each outcome. Nineteen studies were included. Meta-analyses of motor thresholds of the fibularis longus (Z = 1.17, P = 0.24) and soleus (Z = 0.47, P = 0.64) exhibited no differences between ankles with and without CAI. Pooled data indicate that ankles with CAI had reduced soleus spinal reflexive excitability (Z = 2.18, P = 0.03) and significantly less modulation of the soleus (Z = 6.96, P < 0.01) and fibularis longus (Z = 4.75, P < 0.01) spinal reflexive excitability when transitioning to more challenging stances. Pre-synaptic inhibition was facilitated in ankles with CAI (Z = 4.05, P < 0.01), but no difference in recurrent inhibition existed (Z = 1.50, P = 0.13). Soleus spinal reflexive activity is reduced in those with CAI. Reduced ability of ankles with CAI to modulate soleus and fibularis longus reflexive activity may contribute to impaired balance.

Self-healing microcapsules synergetically modulate immunization microenvironments for potent cancer vaccination.

Therapeutic cancer vaccines that harness the immune system to reject cancer cells have shown great promise for cancer treatment. Although a wave of efforts have spurred to improve the therapeutic effect, unfavorable immunization microenvironment along with a complicated preparation process and frequent vaccinations substantially compromise the performance. Here, we report a novel microcapsule-based formulation for high-performance cancer vaccinations. The special self-healing feature provides a mild and efficient paradigm for antigen microencapsulation. After vaccination, these microcapsules create a favorable immunization microenvironment in situ, wherein antigen release kinetics, recruited cell behavior, and acid surrounding work in a synergetic manner. In this case, we can effectively increase the antigen utilization, improve the antigen presentation, and activate antigen presenting cells. As a result, effective T cell response, potent tumor inhibition, antimetastatic effects, and prevention of postsurgical recurrence are achieved with various types of antigens, while neoantigen was encapsuled and evaluated in different tumor models.

Pseurotin A as a novel suppressor of hormone dependent breast cancer progression and recurrence by inhibiting PCSK9 secretion and interaction with LDL receptor

Hypercholesterolemia has been documented to drive hormone-dependent breast cancer (BC) progression and resistance to hormonal therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9) regulates cholesterol metabolism through binding to LDL receptor (LDLR) and targeting the receptor for lysosomal degradation. Inhibition of PCSK9 is an established strategy to treat hypercholesterolemia. Pseurotin A (PS) is a unique spiro-heterocyclic γ-lactam alkaloid isolated from the fungus Aspergillus fumigatus. Preliminary studies indicated that PS lowered PCSK9 secretion in cultured HepG2 hepatocellular carcinoma cells, with an IC50 value of 1.20 μM. Docking studies suggested the ability of PS to bind at the PCSK9 narrow interface pocket that accommodates LDLR. Surface plasmon resonance (SPR) showed PS ability to inhibit the PCSK9-LDLR interaction at a concentration range of 10−150 μM. PS showed in vitro dose-dependent reduction of PCSK9, along with increased LDLR levels in hormone-dependent BT-474 and T47D breast cancer (BC) cell lines. In vivo, daily oral 10 mg/kg PS suppressed the progression of the hormone-dependent BT-474 BC cells in orthotopic nude mouse xenograft model. Immunohistochemistry (IHC) investigation of BT-474 breast tumor tissue proved the PS ability to reduce PCSK9 expression. PS also effectively suppressed BT-474 BC cells locoregional recurrence after primary tumor surgical excision. Western blot analysis showed decreased PCSK9 expression in liver tissues of PS-treated mice compared to vehicle-treated control group. PS treatment significantly reduced PCSK9 expression and normalized LDLR levels in collected primary and recurrent breast tumors at the study end. PS-treated mice showed reduced plasma cholesterol and 17β-estradiol levels. Inhibition of tumor recurrence was associated with significant reductions in plasma level of the human BC recurrence marker CA 15−3 in treated mice at the study end. Histopathological examination of various PS-treated mice organs indicated lack of metastatic tumor cells and any pathological changes. The results of this study provide the first evidence for the suppression of the hormone-dependent breast tumor progression and recurrence by targeting the PCSK9-LDLR axis. PS is a novel first-in-class PCSK9-targeting lead appropriate for the use to control hormone-dependent BC progression and recurrence.

ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma

BackgroundRadioimmunotherapy has a promising antitumor effect in hepatocellular carcinoma (HCC), depending on the regulatory effect of radiotherapy on tumor immune microenvironment. Ionizing radiation (IR)-induced DNA damage repair (DDR) pathway activation...

Fluoride Release from Composite Resin in Different Media

Objective: The present study aimed to measure the released from composite resins stored in different beverages. Materials and Methods: Three composite resins (Te-Econom, Tetric ceram, and VOCO) were used. Twenty specimens for each composite resin were prepared according to the manufacturer instructions, and were divided into four groups (The first group were stowed in deionized water, the second group were stowed in orange juice, the third group were stowed in Pepsi Cola while the last group were stowed in coffee without sugure). The storage solutions were replaced after 7, 15 and 30 days and release (FR) at the end of each storage period was measured by fluoride ion selective electrode. Results: One way analysis and Duncan test were used to statistically analyze the data. The amount of FR from the tested materials was significantly higher in orange juice (at day 15) than the amount of released in coffee and Pepsi Cola. The amount of released from the tested materials was significantly higher in Pepsi cola (at day 7) than the amount of released in orange and Pepsi cola. Conclusion: The ability of restorative dental materials to slowly release ions may provide a positive advantage in terms of recurrent caries inhibition.

Contrast response in a comprehensive network model of macaque V1.

The response to contrast is one of the most important functions of the macaque primary visual cortex, V1, but up to now there has not been an adequate theory for it. To fill this gap in our understanding of cortical function, we built and analyzed a new large-scale, biologically constrained model of the input layer, 4Cα, of macaque V1. We called the new model CSY2. We challenged CSY2 with a three-parameter family of visual stimuli that varied in contrast, orientation, and spatial frequency. CSY2 accurately simulated experimental data and made many new predictions. It accounted for 1) the shapes of firing-rate-versus-contrast functions, 2) orientation and spatial frequency tuning versus contrast, and 3) the approximate contrast-invariance of cortical activity maps. Post-analysis revealed that the mechanisms that were needed to produce the successful simulations of contrast response included strong recurrent excitation and inhibition that find dynamic equilibria across the cortical surface, dynamic feedback between L6 and L4, and synaptic dynamics like inhibitory synaptic depression.

Striatal network modeling in Huntington's Disease.

Medium spiny neurons (MSNs) comprise over 90% of cells in the striatum. In vivo MSNs display coherent burst firing cell assembly activity patterns, even though isolated MSNs do not burst fire intrinsically. This activity is important for the learning and execution of action sequences and is characteristically dysregulated in Huntington's Disease (HD). However, how dysregulation is caused by the various neural pathologies affecting MSNs in HD is unknown. Previous modeling work using simple cell models has shown that cell assembly activity patterns can emerge as a result of MSN inhibitory network interactions. Here, by directly estimating MSN network model parameters from single unit spiking data, we show that a network composed of much more physiologically detailed MSNs provides an excellent quantitative fit to wild type (WT) mouse spiking data, but only when network parameters are appropriate for the striatum. We find the WT MSN network is situated in a regime close to a transition from stable to strongly fluctuating network dynamics. This regime facilitates the generation of low-dimensional slowly varying coherent activity patterns and confers high sensitivity to variations in cortical driving. By re-estimating the model on HD spiking data we discover network parameter modifications are consistent across three very different types of HD mutant mouse models (YAC128, Q175, R6/2). In striking agreement with the known pathophysiology we find feedforward excitatory drive is reduced in HD compared to WT mice, while recurrent inhibition also shows phenotype dependency. We show that these modifications shift the HD MSN network to a sub-optimal regime where higher dimensional incoherent rapidly fluctuating activity predominates. Our results provide insight into a diverse range of experimental findings in HD, including cognitive and motor symptoms, and may suggest new avenues for treatment.

Comparative Study between Magnesium Sulfate and Pethidine for Controlling Shivering after Spinal Anesthesia

Abstract Background Shivering is an involuntary muscular activity. Increased muscle tone during shivering is due to temperature-induced changes in neuronal activity in the reticular formation. Synchronization of motor neurons during shivering may be mediated by recurrent inhibition through renshaw cells. Aim of the Work To verify the efficacy of magnesium sulfate for controlling post spinal shivering, to compare the efficacy of magnesium sulfate and pethidine for controlling post spinal shivering and to detect the side effects of both magnesium sulfate and pethidine after their use for controlling post spinal shivering. Patients and Methods This prospective study was conducted at El-Matarya Teaching Hospital from 2018 till 2019. After obtaining approval from the Research Ethical Committee of Ain Shams University, informed patient consent was obtained before the procedure. After giving the spinal anesthesia, only patients who developed post-spinal shivering were followed for the study. 60 patients with post-spinal shivering were included with the following criteria: Results Regarding age, weight, height and duration of surgery; there were no statistically significant differences between the two studied groups. Comparison of the two studied groups revealed no statistically significant changes at all times of measurement. Conclusion Magnesium sulfate in a dose of 30 mg/kg IV infusion in 100 ml normal saline over 10 min is effective for control of post spinal shivering. Pethidine in a dose of 0.5 mg/kg IV bolus is effective for control of post spinal shivering.

Anti-inflammatory catecholic chitosan hydrogel for rapid surgical trauma healing and subsequent prevention of tumor recurrence

Although occupying pillar position in clinical cancer treatments, surgery itself and surgical trauma would elicit series of local/systemic inflammation-related responses that resulted in high rate of tumor recurrence. Herein, chitosan with conjugated gallic acid (CSG) molecules were coordinated with Fe3+ to form CSG/Fe3+ hydrogel for filling the tumor-resected cavity with considerable wet-adhesion ability and anti-inflammatory performance. With the assistance of doxorubicin hydrochloride (DOX∙HCl), CSG/Fe3+/DOX hydrogel exhibited synergistic photothermal-chemo tumor-inhibited performance under near-infrared (NIR) light irradiation for eradicating residual and/or surgical trauma-recruited cancer cells. Thus, our study attempts to show a paradigm that realizes quick surgical trauma healing, inflammation inhibition and prevention of postsurgical tumor recurrence.

In Situ Photocatalyzed Oxygen Generation with Photosynthetic Bacteria to Enable Robust Immunogenic Photodynamic Therapy in Triple‐Negative Breast Cancer

AbstractHypoxia in the tumor microenvironment is a major hurdle dampening the antitumor effect of photodynamic therapy (PDT). Herein, active photosynthetic bacteria (Synechococcus 7942, Syne) are utilized for tumor‐targeted photosensitizer delivery and in situ photocatalyzed oxygen generation to achieve photosynthesis‐boosted PDT. Photosensitizer‐encapsulated nanoparticles (HSA/ICG) are assembled by intermolecular disulfide crosslinking and attached to the surface of Syne with amide bonds to form a biomimetic system (S/HSA/ICG). S/HSA/ICG combined the photosynthetic capability of Syne and the theranostic effect of HSA/ICG. Syne capable of photoautotrophy exhibit a moderate immune stimulation effect and a certain photodynamic role under 660 nm laser irradiation. Upon intravenous injection into tumor‐bearing mice, S/HSA/ICG can effectively accumulate in tumors and generate oxygen continuously under laser irradiation through photosynthesis, which remarkably relieve tumor hypoxia and enhance reactive oxygen species production, thereby completely eliminating primary tumors. This photosynthesis‐boosted PDT can also effectively reverse the tumor immunosuppressive microenvironment and robustly evoke systematic antitumor immune responses, which exhibit excellent effect on preventing tumor recurrence and metastasis inhibition in a metastatic triple‐negative breast cancer mouse model. Hence, this photosynthetic bacteria‐based photosynthesis‐boosted immunogenic PDT offers a promising approach to eliminate both local and metastatic tumors.