Effective Reactive Oxygen Species Generation Research Articles

Near-Infrared Light-Driving Organic Photothermal Agents with an 88.9% Photothermal Conversion Efficiency for Image-Guided Synergistic Phototherapy.

Photothermal agents (PTAs) with desirable near-infrared (NIR) absorption and excellent photothermal conversion efficiency (PCE) are ideal candidates for cancer treatment. However, numerous PTAs still require high-intensity and long-duration laser irradiation to completely ablate the tumor during the photothermal therapy (PTT) process, resulting in light damage to healthy skin and tissue as well as limiting their biomedical applications. Integrating intense NIR absorption and high PCE into a single small-molecule PTA is an important prerequisite for realizing efficient PTT, but is a serious challenge. Herein, a series of donor-acceptor type PTAs (CC1 to NC4) are designed through a molecular engineering strategy. Theoretical calculations and experimental results show that the NIR absorption and photothermal effect from CC1 to NC4 are significantly enhanced as expected. Notably, NC4 nanoparticles exhibit intense NIR absorption, superhigh PCE of up to 88.9% for PTT, photoacoustic imaging and photothermal imaging, and effective reactive oxygen species generation for photodynamic therapy (PDT). The superior PTT/PDT synergistic phototherapeutic efficacy is well demonstrated by the complete elimination of tumor in vivo upon one-time, low-intensity, and short-duration laser irradiation (808nm, 330mW cm-2, and 3min). This work provides a valuable guideline for rational design of PTAs for cancer phototherapy.

Gas-generating polymersomes-based amplified photoimmunotherapy for abscopal effect and tumor metastasis inhibition

Due to the heterogeneity of tumors, single phototherapy cannot completely ablate tumors and inhibit tumor metastasis. To overcome these, we formulated targeted and multifunctional polymersomes ABC@ICG-IMQ-LHRH (AIRL) that encapsulated Toll-like receptor (TLR) 7/8 agonist imiquimod (IMQ) and photosensitizer indocyanine green (ICG) in the hydrophobic layer as well as bubble-generator NH4HCO3 in the hydrophilic cavity to inhibit the growth of primary and distant tumors, and prevent tumor metastasis through synergistic photoimmunotherapy. The AIRL polymersomes exhibited uniform and stable size, and high drug encapsulation efficiency, acid/reduction/laser responsiveness, excellent photothermal conversion efficiency, effective reactive oxygen species generation, high tumor accumulation. AIRL could be effectively internalized by dendritic cells (DCs), achieve lysosome escape and enhance DCs maturation. The synergistic photoimmunotherapy via AIRL polymersomes remarkably promoted the differentiation and activation of T cells, elevated strong systemic immune response to eradicate primary tumors and inhibit the growth of distant tumors. Simultaneously, the endurable immunological memory prevented tumor metastasis, which provided a promising nanoplatform for the combination therapy of cancer.

A Bioactive Photosensitizer for Hypoxia‐Tolerant Molecular Targeting‐Photo‐Immunotherapy of Malignant Tumor

AbstractPhotosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment of malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency of photodynamic therapy (PDT). Herein, a molecular‐targeting photosensitizer QTANHOH is rationally designed for histone deacetylases (HDACs‐targeting photo‐immunotherapy application. The PS QTANHOH displays excellent type‐I/II PDT performance, exhibiting significant phototoxicity toward cancer cells with half maximal inhibitory concentration (IC50) less than 10 nm in both normoxia and hypoxia conditions under blue laser irradiation. Moreover, the bioactive compound could inhibit HDACs and activate the immune microenvironment to boost PDT efficacy on the immunocompetent BALB/c mice with breast cancer, leading to the eradication of solid tumor and inhibition of metastasis. Notably, the molecular‐targeting photosensitizer introduces an alternative strategy to achieve superior phototherapy for cancer therapy.

Prolongation excitation wavelength of two-photon active photosensitizer for near-infrared light-induced in vitro photodynamic therapy

The construction of novel photosensitizer for effective reactive oxygen species generation has attracted extensive interest, in particular the design of a new photosensitizer with long excitation wavelength remains challenge. In this paper, we design a novel two-photon active Ruthenium(II) complex (RuL1) based on donor-acceptor configuration ligand. Notably, benefiting from the coordination of Ru ion, the electron transfer between donor and acceptor moiety gave rise to enhanced two-photon activity and prolonged excitation wavelength. The results showed that RuL1 exhibited excellent two-photon activity under near-infrared light excitation (920 nm), which provided a potential platform for photodynamic therapy in “therapeutic window”.

Mechanochemical activation of zero-valent iron on carbonized boron-doped graphene dots for enhanced sonochemical dyes removal

Boron-doped graphene dots (BGDs) were synthesized by a hydrothermal method using the disaccharide maltose as the carbon precursor and borax as the boron dopant. The precursors were heated to 500 °C for 5 h to obtain the carbonized BGDs (CBGDs). B doping was carried out to increase the surface area and improve the electron transfer reaction for quick and effective reactive oxygen species generation. BGDs and CBDGs showed different oxygen contents and functionalities, surface areas, morphologies, and zeta-potentials. Zero-valent iron (ZVI) was activated mechanochemically by surface passivation using BGDs and CBGDs under atmospheric conditions, and their dye removal performance via sonochemical degradation was evaluated. Owing to the greater oxygen functionality of BGDs, the ZVI@BGDs were fully decorated with ZVI, and less activation occurred that inhibited the sonochemical dye degradation properties of ZVI@BGDs. In contrast, a sheet-like structure and activation of ZVI on ZVI@CBGDs make it an active catalyst. The maximum surface area (413.82 m2/g) and high negative zeta potential (−38.25 mV) of CBGDs make it a good adsorbent. BGDs have a low surface area (20.78 m2/g), self-assembling structure, non-planer arrangement, and a twisted structure with interlocking spheres that disfavor π–π stacking between the dye and BGDs and make it non-adsorbent. The rapid generation of reactive oxygen species, the existence of iron with mixed-valence states, and the increase in surface area due to boron doping facilitate the electron transfer process to make the catalyst active and reusable even after 10 cycles.

One-for-All Phototheranostic Agent Based on Aggregation-Induced Emission Characteristics for Multimodal Imaging-Guided Synergistic Photodynamic/Photothermal Cancer Therapy

Phototheranostics represents a promising direction for modern precision medicine, which has recently received considerable attention for cancer research. The ingenious integration of all phototheranostic modalities in a single molecule with precise spatial colocalization is a tremendously challenging task, which mainly arises from the complexity of molecular design and energy dissipation. Reports on a single molecular one-for-all theranostic agent are still very rare. Herein, we designed two novel aggregation-induced emission (AIE)-active fluorogens (AIEgens, named DPMD and TPMD) with a cross-shaped donor-acceptor structure via a facile synthetic method and constructed versatile nanoparticles (NPs) by encapsulating AIEgen with an amphiphilic polymer. The AIEgen TPMD with a twisted structure, high donor-acceptor (D-A) strength, small singlet-triplet energy gap, and abundant intramolecular rotators and vibrators was selected as an ideal candidate for balancing and utilizing the radiative and nonradiative energy dissipations. Notably, TPMD NPs simultaneously possess adequate near-infrared (NIR) fluorescence emission at 821 nm for fluorescence imaging, effective reactive oxygen species generation for photodynamic therapy (PDT), and outstanding photothermal effect for photoacoustic imaging, photothermal imaging, and photothermal therapy (PTT), which demonstrates the superior potential of AIE NPs in multimodal imaging-guided synergistic PDT/PTT therapy.

Zwitterionic AIEgens: Rational Molecular Design for NIR‐II Fluorescence Imaging‐Guided Synergistic Phototherapy

AbstractFluorescence imaging in the second near‐infrared region (NIR‐II) can penetrate tissue at centimeter depths and obtain high image fidelity. However, facile synthesis of small‐molecule fluorescent photosensitizers for efficient NIR‐II fluorescence imaging as well as photodynamic and photothermal combinatorial therapies is still a challenging task. Herein, a rational design and facile synthesis protocol are reported for a series of novel NIR‐emissive zwitterionic luminogens with aggregation‐induced emission (AIE) features for cancer phototheranostics. Consistent with the intrinsic features including long emission wavelength, effective reactive oxygen species generation, and excellent photothermal conversion efficiency (35.76%), in vitro and in vivo evaluation show that one of these presented AIE luminogens provides excellent performance in NIR‐II fluorescence imaging‐guided synergistic phototherapy against cancer.

Biodegradable Natural Product-Based Nanoparticles for Near-Infrared Fluorescence Imaging-Guided Sonodynamic Therapy

Natural products show high potential for clinical translation because of their specific biological activities and molecular structure diversities. Sonosensitizers that originate from natural products play a crucial role as anti-inflammatory and anticancer agents. Herein, hypocrellin-derivative nanoparticles (APHB NPs) were constructed for synchronous near-infrared fluorescence (NIR FL) imaging and sonodynamic therapy (SDT) for deep-seated tumors in vivo. The prepared APHB NPs exhibit excellent water solubility, FL in the NIR region, and effective reactive oxygen species generation under ultrasound stimulation. Furthermore, the APHB NPs show excellent biocompatibility, suitable biodegradation rate, and enhanced tumor accumulation. Therefore, the APHB NPs exhibit promising clinical potential as novel safe and precise NIR FL imaging and SDT agents for deep-seated tumor therapy.

Graphene Oxide⁻Platinum Nanoparticle Nanocomposites: A Suitable Biocompatible Therapeutic Agent for Prostate Cancer.

Metal nanoparticles and the combination of metal nanoparticles with graphene oxide are widely used in environmental, agriculture, textile, and therapeutic applications. The effect of graphene oxide–green platinum nanoparticles (GO-PtNPs) on human prostate cancer cells (LNCaP) is unclear. Therefore, this study aimed to synthesize a nanocomposite of GO-PtNPs and evaluate their effect on prostate cancer cells. Herein, we synthesized GO-PtNPs using vanillin and characterized GO-PtNPs. GO-PtNP cytotoxicity in LNCaP cells was demonstrated by measuring cell viability and proliferation. Both decreased in a dose-dependent manner compared to that by GO or PtNPs alone. GO-PtNP cytotoxicity was confirmed by increased lactate dehydrogenase release and membrane integrity loss. Oxidative stress induced by GO-PtNPs increased malondialdehyde, nitric oxide, and protein carbonyl contents. The effective reactive oxygen species generation impaired the cellular redox balance and eventually impaired mitochondria by decreasing the membrane potential and ATP level. The cytotoxicity to LNCaP cells was correlated with increased expression of proapoptotic genes (p53, p21, Bax, Bak, caspase 9, and caspase 3) and decreased levels of antiapoptotic genes (Bcl2 and Bcl-xl). Activation of the key regulators p53 and p21 inhibited the cyclin-dependent kinases Cdk2 and Cdk4, suggesting that p53 and p21 activation in GO-PtNP-treated cells caused genotoxic stress and apoptosis. The increased expression of genes involved in cell cycle arrest and DNA damage and repair, and increased levels of 8-oxo-deoxyguanosine and 8-oxoguanine suggested that GO-PtNPs potentially induce oxidative damage to DNA. Thus, GO-PtNPs are both cytotoxic and genotoxic. LNCaP cells appear to be more susceptible to GO-PtNPs than to GO or PtNPs. Therefore, GO-PtNPs have potential as an alternate and effective cancer therapeutic agent. Finally, this work shows that the combination of graphene oxide with platinum nanoparticles opens new perspectives in cancer therapy. However further detailed mechanistic studies are required to elucidate the molecular mechanism of GO-PtNPs induced cytotoxicity in prostate cancer.

Relationships Between Crystal, Internal Microstructures, and Physicochemical Properties of Copper-Zinc-Iron Multinary Spinel Hierarchical Nano-microspheres.

Rational design and fabrication of high quality complex multicomponent spinel ferrite with specific microstructures and solar light harvestings toward CO2 reduction and antibiotic degradation to future energetic and catalytic applications are highly desirable. In this study, novel copper-zinc-iron multinary spinel hierarchical nano-microspheres (MSHMs) with different internal structures (solid nano-microspheres, yolk-shell hollow nano-microspheres, and double-shelled hollow nano-microspheres) have been successfully developed by a facile self-templated solvothermal strategy. The morphology and structure, optical, as well as photoinduced redox reactions including interfacial charge carrier behaviors and the intrinsic relationship of structure-property between intrinsic nano-microstructures and physicochemical performance of copper-zinc-iron ferrite MSHMs composites were systematically investigated with the assistance of various on- and/or off- line physical-chemical means and deeply elucidated in terms of the research outcomes. It is demonstrated that the modification of the interior microstructures can be applied to tune the catalytic properties of multinary spinel by tailoring the temperature programming to fine control the two opposite forces of contraction (Fc) and adhesion (Fa). Among various internal microstructures, the obtained double-shelled copper-zinc-iron MSHMs exhibited the superior catalytic performance toward 8.8 and 38 μmol for H2 and CO productions as well as 80.4% removal of sulfamethoxazole antibiotics. As evidenced from primary characterizations, for example, combined steady-state PL, ns-TAS, and Mössbauer and sequential investigations, the remarkable improvements in the catalytic activity can be primarily attributed to several crucial factors, for example, the more effective e--h+ spatial separations and interfacial transfers, multiple internal light scattering, higher photonic energy harvesting and effective reactive oxygen species generation with long radical lifetimes. The current research provides new insights into the molecular design of novel copper-zinc-iron multinary spinels and the intrinsic relationship of structure-property between interior structures (e.g., different crystal texture, morphologies structures) and the physicochemical performance of the aforementioned multinary spinels.