Calcium-enriched carbon nanoparticles loaded with indocyanine green for near-infrared fluorescence imaging-guided synergistic calcium overload, photothermal therapy, and glutathione-depletion-enhanced photodynamic therapy.

Combining phototherapy with other treatments has significantly advanced cancer therapy. Here, we designed and fabricated calcium-enriched carbon nanoparticles (Ca-CNPs) that could effectively deplete glutathione (GSH) and release calcium ions in tumors, thereby enhancing the efficacy of photodynamic therapy (PDT) and the calcium overload effect that leads to mitochondrial dysfunction. Due to the electrostatic interaction, π-π stacking interaction, multiple hydrogen bonds, and microporous structures, indocyanine green (ICG) was loaded onto the surface of Ca-CNPs with a high loading efficiency of 44.7 wt%. The obtained Ca-CNPs@ICG can effectively improve the photostability of ICG while retaining its ability to generate singlet oxygen (1O2) and undergo photothermal conversion (Ca-CNPs@ICG vs. ICG, 45.1% vs. 39.5%). In vitro and in vivo experiments demonstrated that Ca-CNPs@ICG could be used for near-infrared fluorescence imaging-guided synergistic calcium overload, photothermal therapy, and GSH depletion-enhanced PDT. This study sheds light on the improvement of 1O2 utilization efficiency and calcium overload-induced mitochondrial membrane potential imbalance in tumor cells.

Intramolecular cascade reaction sensing platform for rapid, specific and ultrasensitive detection of nitrite.

Nitrite is a carcinogenic substance in food. Excessive consumption of nitrite severely endangers human health. However, rapid and accurate quantification of nitrite by a simple tool is still very challenging. In this work, we designed a practical sensing platform based on 8-(o-phenylenediamine)-boron dipyrromethene (BDP-OPD) to determine nitrite in food. BDP-OPD can take a specific diazotization-cyclization cascade reaction with nitrite to form boron dipyrromethene (BODIPY), giving rise to a remarkable chromogenic reaction along with high contrast fluorescence turn-on response towards nitrite. BDP-OPD has high sensitivity, rapid response, and good selectivity. Furthermore, a portable smartphone-based fluorescence device integrated with a self-programmed Python program was fabricated, which has been successfully used to determine nitrite in food with the advantages of rapid response, low cost, ease of operation, portability, and satisfactory recoveries (92-112%). The good sensing performance rendered BDP-OPD a promising fluorescence platform for on-site visual detection of nitrite.

Catalase-like pleated niobium carbide MXene loaded with polythiophene for oxygenated sonodynamic therapy in solid tumor.

Sonodynamic therapy (SDT), an emerging treatment for solid tumors, has the advantages of deep tissue penetration, non-invasiveness, low side effects, and negligible drug resistance. However, the hypoxic environment of deep solid tumors can discount the efficacy of oxygenated dependent SDT. Here, we synthesized a polythiophene-based sonosensitizer (PT2) and a two-dimensional pleated niobium carbide (Nb2C) Mxene. PT2 was loaded onto the surface of poly(vinylpyrrolidone) (PVP)-coated Nb2C MXene through electrostatic interaction to obtain Nb2C-PVP-PT2 nanosheets (NSs) with a high loading efficiency of 153.7%. Nb2C MXene exhibited catalase-like activity, which could catalyze hydrogen peroxide (H2O2) to produce O2, in turn alleviating tumor hypoxia and enhancing the efficacy of SDT. The depletion of H2O2 further results in abnormal cellular H2O2 levels and reduced tumor cell activity. Moreover, the decomposed NSs led to the release of the sonosensitizer PT2 that can efficiently generate both singlet oxygen and superoxide anions under ultrasound irradiation. These events led to the inhibition of DNA replication of tumor cells, causing tumor cell death, allowing for enhanced SDT efficacy.

Vascular disruption agent and phototherapeutic assembled nanoparticles for enhanced tumor inhibition.

Vascular disruption agent (combretastatin A-4 phosphate) and phototherapeutic (IEICO-4F) assembled nanoparticles (IFC NPs) were prepared for the first time. The IFC NPs have a high photo energy utilization efficiency of up to 96.1%, and could significantly inhibit tumor growth by photodynamic and photothermal therapy enhanced tumor vascular disruption.

Lysosome- and plasma membrane-accumulative and tumor-targetable polythiophene nanoparticles for enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) has emerged as a promising treatment approach of solid tumors given its deep tissue penetration, non-invasiveness, few side effects, and negligible drug resistance. Herein, we report the first polythiophene derivative-based sonosensitizer (PT2) containing a quaternary ammonium salt and dodecyl chains with better ultrasound stability than that of traditional sonosensitizers, such as Rose Bengal and chlorin e6. PT2 was encapsulated by folic acid-containing polyethylene glycol. The obtained nanoparticles (PDPF NPs) exhibited excellent biocompatibility, cancer cell-targeting capacity, and accumulated mainly in the lysosomes and plasma membranes of cells. These NPs could generate singlet oxygen and superoxide anions simultaneously under ultrasound irradiation. In vitro and in vivo experimental results demonstrated that PDPF NPs could induce cancer-cell death through apoptosis and necrosis, inhibit DNA replication, and ultimately achieve tumor depletion upon US irradiation. These findings revealed that polythiophene could serve as an efficacious sonosensitizer for enhanced US treatment of deep-seated tumors.

Regulating photochemical properties of carbon dots for theranostic applications.

As a new zero-dimensional carbon-based material, carbon dots (CDs) have attracted extensive attention owing to their advantages such as easy preparation and surface modification, good biocompatibility and water solubility, and tunable photochemical properties. CDs have become one of the most promising nanomaterials in the field of fluorescent sensing, bioimaging, and cancer therapy. How to precisely regulate the photochemical properties, especially the absorption, fluorescence, phosphorescence, reactive oxygen species generation, and photothermal conversion of the CDs, is the key to developing highly efficient phototheranostics for cancer treatment. Although many studies on cancer therapy using CDs have been published, no review has focused on the regulation of photochemical properties of CDs for phototheranostic applications. In this review, we summarized the strategies such as the selection of suitable carbon source, heteroatomic doping, optimum reaction conditions, surface modification, and assembly strategy to efficiently regulate the photochemical properties of the CDs to meet the requirements of different practical applications. This review might provide some valuable insight and new ideas for the development of CDs with excellent phototheranostic performance. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

A water-soluble thiophene-croconaine dye with a high molar extinction coefficient for NIR fluorescence imaging-guided synergistic photothermal/photodynamic therapy of cancer.

Phototherapeutic agents with near-infrared (NIR) fluorescence, strong reactive oxygen species generation and photothermal conversion capabilities are highly desirable for use in cancer therapy. Herein, a water-soluble NIR croconaine dye (TCR) with a thiophene-croconaine rigid core and two symmetric alkyl chains was designed and synthesized. TCR exhibits intense NIR absorption and fluorescence that peaked at 780 and 815 nm, respectively, with a high molar extinction coefficient of 1.19 × 105 M-1 cm-1. Moreover, TCR has a high photothermal conversion efficiency of 77% and is capable of generating hydroxyl radicals (OH˙) under 735 nm laser irradiation. Based on these outstanding properties, TCR has proven its application in NIR fluorescence imaging-guided synergistic photothermal/photodynamic therapy of cancer.

Tumor microenvironment-responsive S-NSs-TPZ-ICG intelligent nanoplatforms for synergistically enhanced tumor multimodal therapy.

Nanosheet carriers loaded with drugs and phototherapeutics are used for effective cancer therapy, but the process remains challenging. Here, we prepared sulfur nanosheets (S-NSs) and then loaded tirapazamine (TPZ) and indocyanine green (ICG) with a loading efficiency of 6.3% and 94%, respectively. The obtained S-NSs-TPZ-ICG exhibits near-infrared (NIR) fluorescence, high 1O2 generation and photothermal conversion capabilities, good biocompatibility, and tumor microenvironment responsiveness. In vivo and in vitro experiments reveal that S-NSs-TPZ-ICG can be selectively decomposed under acidic and H2O2 conditions to release TPZ and ICG, and significantly inhibit tumor growth under laser irradiation without obvious toxic side effects.

A-DA'D-A Structured Organic Phototheranostics for NIR-II Fluorescence/Photoacoustic Imaging-Guided Photothermal and Photodynamic Synergistic Therapy.

Multimodal imaging-guided combinational phototherapies triggered by a single near-infrared (NIR) laser are highly desirable. However, their development is still a big challenge. Herein, we have developed an "acceptor-donor-acceptor'-donor-acceptor" structured organic phototheranostics (Y16-Pr) with strong light-harvesting ability in the NIR region. After being modified with polyethylene glycol (PEG), the obtained biocompatible nanoparticles (Y16-Pr-PEG NPs) could conduct NIR-II fluorescence imaging (FLI) and photoacoustic imaging (PAI) and perform photothermal therapy (PTT) and photodynamic therapy (PDT) simultaneously. Notably, Y16-Pr-PEG NPs showed an impressive photothermal conversion efficiency (PCE) of 82.4% under 808 nm laser irradiation. The irradiated NPs could also produce hydroxyl radicals (•OH) and singlet oxygen (1O2) for type I and type II PDT, respectively. In vivo and in vitro experiments revealed that the Y16-Pr-PEG NPs significantly inhibit tumor cell growth without apparent toxic side effects under laser irradiation. Overall, the single-laser-triggered multifunctional phototheranostic Y16-Pr-PEG NPs can achieve NIR-II FLI/PAI-guided synergistic PTT/PDT against tumors.

Near-Infrared Light-Triggered Lysosome-Targetable Carbon Dots for Photothermal Therapy of Cancer.

Photothermal therapy (PTT) has inherent advantages in the treatment of hypoxic tumors due to its optically controlled selectivity on tumor ablation and oxygen-independent nature. The subcellular organelle-targeting capability and photothermal conversion efficiency (PCE) at near-infrared (NIR) wavelength are the key parameters in the assessment of the photothermal agent (PTA). Here, we report that carbon dots (CDs) prepared by the hydrothermal treatment of coronene derivatives show a high PCE of 54.7% at 808 nm, which can be attributed to the narrow band gap and the presence of amounts of continuous energy bands on CDs. Moreover, the vibrations in the layered graphite structures of the CDs also increase the rate of nonradiative transition and thus enhance the PCE. Furthermore, the CDs also possess excellent photostability, biocompatibility, and cell penetration capability and could mainly accumulate in the lysosomes. These experiment results have proved that the CDs are suitable as an efficient NIR light-triggered PTA for efficient PTT against cancer.

An Iridium Complex as an AIE-active Photosensitizer for Image-guided Photodynamic Therapy.

Image-guided photodynamic therapy (PDT) has received growing attention due to its non-invasiveness and precise controllability. However, the PDT efficiency of most photosensitizers are decreased in living system due to the aggregation-caused singlet oxygen (1 O2 ) generation decreasing. Herein, we present an Iridium (III) pyridylpyrrole complex (Ir-1) featuring of aggregation-induced emission (AIE) and 1 O2 generation characteristics for image-guided PDT of cancer. Ir-1 aqueous solution exhibits bright red phosphorescence peaked at 630 nm, large Stokes shift of 227 nm, and good 1 O2 generation ability. The 1 O2 generating rate of Ir-1 in EtOH/water mixture solution is 2.3 times higher than that of Rose Bengal. In vitro experimental results revealed that Ir-1 has better biocompatibility and higher phototoxicity compared with clinically used photosensitizers (Rose Bengal and Ce6), suggesting that Ir-1 can serve as a photosensitizer for image-guided PDT of cancer.

Advances and perspectives in carrier-free nanodrugs for cancer chemo-monotherapy and combination therapy.

Nanocarrier-based drug delivery systems hold impressive promise for biomedical application because of their excellent water dispersibility, prolonged blood circulation time, increased drug accumulation in tumors, and potential in combination therapeutics. However, most nanocarriers suffer from low drug-loading efficiency, poor therapeutic effectiveness, potential systematic toxicity, and unstable metabolism. As an alternative, carrier-free nanodrugs, completely formulated with one or more drugs, have attracted increasing attention in cancer therapy due to their advantage of improved pharmacodynamics/pharmacokinetics, reduced toxicity, and high drug-loading. In recent years, carrier-free nanodrugs have contributed to progress in a variety of therapeutic modalities. In this review, different common strategies for carrier-free nanodrugs preparation are first summarized, mainly including nanoprecipitation, template-assisted nanoprecipitation, thin-film hydration, spray-drying technique, supercritical fluid (SCF) technique, and wet media milling. Then we describe the recently reported carrier-free nanodrugs for cancer chemo-monotherapy or combination therapy. The advantages of anti-cancer drugs combined with other chemotherapeutic, photosensitizers, photothermal, immunotherapeutic or gene drugs have been demonstrated. Finally, a future perspective is introduced to highlight the existing challenges and possible solutions toward clinical application of currently developed carrier-free nanodrugs, which may be instructive to the design of effective carrier-free regimens in the future.

Photosensitizers for Photodynamic Therapy.

As an emerging clinical modality for cancer treatment, photodynamic therapy (PDT) takes advantage of the cytotoxic activity of reactive oxygen species (ROS) that are generated by light irradiating photosensitizers (PSs) in the presence of oxygen (O2 ). However, further advancements including tumor selectivity and ROS generation efficiency are still required. Substantial efforts are devoted to design and synthesize smart PSs with optimized properties for achieving a desirable therapeutic efficacy. This review summarizes the recent progress in developing intelligent PSs for efficient PDT, ranging from single molecules to delicate nanomaterials. The strategies to improve ROS generation through optimizing photoinduced electron transfer and energy transfer processes of PSs are highlighted. Moreover, the approaches that combine PDT with other therapeutics (e.g., chemotherapy, photothermal therapy, and radiotherapy) and the targeted delivery in cancer cells or tumor tissue are introduced. The main challenges for the clinical application of PSs are also discussed.

Water-Soluble Polythiophene for Two-Photon Excitation Fluorescence Imaging and Photodynamic Therapy of Cancer.

Positively charged water-soluble polythiophene (PT0) that could self-assemble into nanoparticles in pure water solution was designed and synthesized. PT0 exhibited high photostabilities and pH stabilities, excellent biocompatibility, strong 1O2 generation capability, and large two-photon absorption cross sections. Moreover, we showed that the fluorescence of PT0 was unaffected by the interference of biomolecules and metal ions. As an example application, PT0 was demonstrated to be capable of simultaneous cell imaging and photodynamic therapy under either one-photon or two-photon excitation modes.

Green Synthesis of Bifunctional Fluorescent Carbon Dots from Garlic for Cellular Imaging and Free Radical Scavenging.

Nitrogen and sulfur codoped carbon dots (CDs) were prepared from garlic by a hydrothermal method. The as-prepared CDs possess good water dispersibility, strong blue fluorescence emission with a fluorescent quantum yield of 17.5%, and excellent photo and pH stabilities. It is also demonstrated that the fluorescence of CDs are resistant to the interference of metal ions, biomolecules, and high ionic strength environments. Combining with low cytotoxicity properties, CDs could be used as an excellent fluorescent probe for cellular multicolor imaging. Moreover, the CDs were also demonstrated to exhibit favorable radical scavenging activity.