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Heptamethine cyanine dyes are widely used for in vivo near-infrared (NIR) fluorescence imaging and NIR laser-induced cancer phototherapy due to their good optical properties. Since most of heptamethine cyanine dyes available commercially are highly hydrophobic, they can usually be used for in vivo applications after formation of complexes with blood plasma proteins, especially serum albumin, to increase aqueous solubility. The complex formation between cyanine dyes and albumin improves the chemical stability and optical property of the hydrophobic cyanine dyes, which is the bottom of their practical use. In this study, the complexes between three different heptamethine cyanine dyes, namely clinically available indocyanine green (ICG), commercially available IR-786 and zwitterionic ZW800-Cl, and bovine serum albumin (BSA), were prepared to explore the effect of cyanine dyes on their tumor uptake and retention. Among the three complexes, IR-786©BSA exhibited increased tumor accumulation with prolonged tumor retention, compared to other complexes. Moreover, IR-786 bound to BSA played an important role in tumor growth suppression due to its cytotoxicity. To achieve complete tumor ablation, the tumor targeted by IR-786©BSA was further exposed to 808 nm laser irradiation for effective photothermal cancer treatment.

Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores conjugated with hydrophobic anticancer drugs is an important consideration for targeted cancer photothermal therapy (PTT). In this study, a highly water-soluble zwitterionic NIR fluorophore (ZW800) was prepared to conjugate with a water-insoluble anticancer drug, chlorambucil (CLB), to improve tumor targeting, in vivo biodistribution, and PTT performance. The in vivo results using an HT-29 xenograft mouse model demonstrated that the CLB-ZW800 conjugate not only exhibited high tumor accumulation within 4 h after injection, but also showed rapid body clearance behavior for less systemic toxicity. Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore.

To overcome the limitations of brown adipose tissue (BAT) imaging with MRI and PET/CT, near-infrared (NIR) fluorescence imaging has been utilized in living animals because it is highly sensitive, noninvasive, nonradioactive, and cost-effective. To date, only a few NIR fluorescent dyes for detecting BAT have been reported based on the structure-inherent targeting strategy. Among them, IR-786, a commercial cyanine dye, was used firstly for quantitative NIR imaging of BAT perfusion in 2003. Owing to the high cytotoxicity, poor water solubility, and strong nonspecific background uptake of IR-786, the chemical structure of IR-786 should be redesigned to be more hydrophilic and less toxic so that it can show more BAT-specific accumulation. Here, we developed a BAT-specific NIR dye, BF800-AM, by incorporating the tyramine linker in the original structure of IR-786. After modifying the physicochemical properties of IR-786, in vivo results showed significant uptake of the newly designed BF800-AM in the BAT with improved signal-to-background ratio. Additional in vivo studies using mouse tumor models revealed that BF800-AM targeting to BAT is independent of tumor tissues, as distinct from IR-786 showing uptake in both tissues. Therefore, BF800-AM can be used for improved noninvasive visualization of BAT mass and activity in living animals.

Since carbon dots (CDs) exhibit excellent biocompatibility, low cytotoxicity, near-infrared (NIR) absorbance, and superior photostability, many types of CDs are considered as powerful candidates for photothermal therapy (PTT) applications. However, the development of a desirable CD is still difficult due to insufficient photothermal conversion, thus resulting in the use of high laser power densities at a high dose of CDs for the PTT effect. Herein, bioinspired sulfur-doped CDs (S-CDs) with strong NIR absorbance were prepared from Camellia japonica flowers via a facile hydrothermal method for enhancing the photothermal conversion efficiency. The as-prepared S-CDs exhibited various advantages including cost-effective preparation, good water-solubility, high biocompatibility, intense NIR absorption, and excellent photothermal effect with robust photostability. Most importantly, the optimal low dose of S-CDs (45 μg mL−1) successfully led to efficient PTT performance with a high photothermal conversion efficiency (55.4%) under moderate laser power (808 nm, 1.1 W cm−2) for safe and effective cancer therapy.

Since carbon dots (CDs) exhibit excellent biocompatibility, low cytotoxicity, near-infrared (NIR) absorbance, and superior photostability, many types of CDs are considered as powerful candidates for photothermal therapy (PTT) applications. However, the development of a desirable CD is still difficult due to insufficient photothermal conversion, thus resulting in the use of high laser power densities at a high dose of CDs for the PTT effect. Herein, bioinspired sulfur-doped CDs (S-CDs) with strong NIR absorbance were prepared from

The combination of near-infrared (NIR) fluorophores and photothermal therapy (PTT) provides a new opportunity for safe and effective cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high tumor targetability was developed for efficient photothermal cancer therapy. The isoniazid (INH)–ZW800-1 conjugate (INH–ZW) was synthesized by conjugating an antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided cancer phototherapy. INH–ZW not only showed rapid tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce cancer cell death under NIR laser irradiation. Compared with previously reported ZW800-1 conjugates, INH–ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved tumor targeting and PTT. Together, these results demonstrate that the INH–ZW conjugate has great potential to serve as an effective PTT agent capable of rapid tumor targeting and high renal clearance, with excellent photothermal efficacy.

A tumor-targeted near-infrared (NIR) fluorophore CA800SO3 was developed for fluorescence-guided phototherapy. This new type of NIR fluorophore showed high tumor targetability based on the structure-inherent targeting approach. This fluorophore generated sufficient hyperthermia and reactive oxygen species (ROS) simultaneously for synergistic cancer phototherapy, induced by an 808 nm laser irradiation.

BACKGROUND: For the bone-specific imaging, a structure-inherent targeting of bone tissue recently has been reported a new strategy based on incorporation of targeting moieties into the chemical structure of near-infrared (NIR) contrast agents, while conventional methods require covalent conjugation of bone-targeting ligands to NIR contrast agents. This will be a new approach for bone-targeted imaging by using the bifunctional NIR contrast agents. METHODS: The goal of this review is to provide an overview of the recent advances in optical imaging of bone tissue, highlighting the structure-inherent targeting by developing NIR contrast agents without the need for a bone-targeting ligand such as bisphosphonates. RESULTS: A series of iminodiacetated and phosphonated NIR contrast agents for the structure-inherent targeting of bone tissue showed excellent bone-targeting ability in vivo without non-specific binding. Additionally, the phosphonated NIR contrast agents could be useful in the diagnosis of bone metastasis. CONCLUSION: By developing bone-targeted NIR contrast agents, optical imaging of bone tissue makes it very attractive for preclinical studies of bone growth or real-time fluorescence guided surgery resulting in high potential to shift the clinical paradigms.

Cancer is one of the leading causes of death in human beings. Therefore, it is important to detect specific target tumors earlier enough in the formative stages of cancer without causing negative side effects and damages to the body. In this study, we proposed bio-engineered short mussel adhesive proteins (MAPs)-carbon nanotubes (CNTs) as specific tumor-targeted carriers for biomedical imaging. Short CNT near-infrared fluorophore (NIRF) hybrid carriers that were developed accumulated in the tumors with exceptional clearance and specific targeting in less time, and these results indicated that bioengineered short CNT-based carriers have great potential for real time tumor imaging.

We prepared a drug carrier which consisted of injectable methacrylated glycol chitosan (MGC) hydrogel, and a conjugate of 6-monodeoxy-6-monoamino-&beta, cyclodextrin&sdot, hydrochloride (6-NH2-&beta, CD&sdot, HCl), polyethylene glycol (PEG), and folic acid (FA) for the local delivery and improved cellular uptake of paclitaxel (PTX) (MGC/CDPF-ic-PTX). CDPF refers to a conjugate of 6-NH2-&beta, HCl, PEG, and FA. The anti-cancer effect was investigated using a xenograft mouse model. As controls, the animal study on MGC/PTX and MGC/CD-ic-PTX was performed. The swelling ratio of all samples was analyzed for 7 days, and it showed a gradual increase for 3 days and a maintained state afterward. From the release result, the MGC-based samples have an initial burst for 1 day and a sustained release for 7 days. Results of cytotoxicity and animal study showed the biocompatibility and superior anti-cancer effect of MGC/CDPF-ic-PTX against breast cancer. Furthermore, histological results showed the anti-cancer capacity of MGC/CDPF-ic-PTX against breast cancer. These findings suggest that MGC/CDPF-ic-PTX has clinical potential for breast cancer therapy.

Photothermal therapy (PTT) is a promising approach for effective cancer treatment because of its non-invasive procedure, low toxicity to normal tissues, and high tumour ablation efficiency. Developing a PTT agent with precise tumour imaging capabilities is an essential prerequisite for effective PTT. In this study, we developed a bifunctional near-infra-red (NIR) fluorescent conjugate consisting of chitosan oligosaccharide lactate (COL) and the ZW800-1 NIR fluorophore (COL-ZW). We demonstrate that this conjugate is easy to use and that it is an effective theranostic agent for fluorescence-guided photothermal treatment. The temperature of COL-ZW increased by 62.3 °C after NIR laser irradiation (1.1 W/cm

In this study, we prepared a beta-cyclodextrin (β-CD)-based carrier consisting of β-CD, polyethylene glycol (PEG) and folic acid (FA) (CDPF) for improved doxorubicin (DOX) delivery to targeted breast cancer in vitro and in vivo. The morphology and size distribution were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements, which revealed in particles ranging from 38 nm to 52 nm in size. DOX from CDPF was released in a sustained manner for 48 h. Cell viability analysis showed the low toxicity of free DOX, whereas CDPF-DOX remarkably exhibited reduced viability after incubation for 7 days. In vivo animal test showed that intravenous injection of CDPF-DOX contributes to decreased tumor volume, along with no systemic toxicity and cardiotoxicity. The results suggested that CDPF can maximize the efficacy of DOX delivery; therefore can be used as a good candidate for developing optimal drug delivery systems.

Precise photothermal cancer therapy still relies on the development of multifunctional theranostic agents to integrate tumor-specific targeting, imaging, and therapy. In this study, we identified the zwitterionic near-infrared (NIR) fluorophore ZW800-Cl, an analog of the well-known ZW800-1, and found that it preferentially accumulated in tumors in various xenograft models. We have demonstrated that the optical and physicochemical properties of ZW800-Cl are similar to those of ZW800-1, but it has a unique tumor targetability. Since ZW800-Cl showed binding selectivity to cancer cells in vitro, it could be specifically targeted to xenograft models of multiple tumor types, including MCF-7, NCI-H460, and HT-29. The in vivo results of photothermal cancer therapy indicated that the xenograft tumors could be effectively ablated by the combination of ZW800-Cl and an 808 nm laser irradiation. In this regard, our finding may provide a new approach for developing multifunctional cancer theranostic agents, setting them apart from conventional nanoparticles based on inorganic and polymeric materials. Therefore, ZW800-Cl may hold promise as a multifunctional theranostic agent for tumor-targeted imaging and effective photothermal cancer therapy.

This study evaluated the near-infrared (NIR) fluorescent probe Sorbitol-ZW800-1 as tracer for targeted tumor imaging of multiple cancer types. Preliminarily, Sorbitol-ZW800-1 conjugate was validated in vivo on breast (MCF-7) cancer cell lines. Subsequently, the tracer was tested in xenograft mouse models with malignant breast (MDA-MB-231), lung (NCI-H460), and colorectal (HT-29) tumors, respectively. Importantly, the Sorbitol-ZW800-1 conjugate showed highly selective tumor uptake in various tumor mice models. Moreover, biodistribution for 24 h exhibited the significant fluorescence signals in tumors and kidneys. Therefore, sorbitol is a promising candidate as a potential cancer targeting agent for the accurate detection of cancer cells.

Bioluminescence imaging is being increasingly utilized in biological research. However, since the most commonly used firefly luciferase generates relatively weak bioluminescent signals, detection of low numbers of luciferase-expressing cells in vivo is challenging. The weak signal makes it difficult to detect cells located in deep tissues, which is problematic for preclinical research in tumor metastasis. In this study, three different types of fluorophores such as D-luciferin, AkaLumine-HCl, and P800SO3 were compared to evaluate the progression of bone metastasis induced by MDA-MB-231 breast cancer cells in vivo. The fluorescent signals for D-luciferin, AkaLumine-HCl, and P800SO3 were differently detected in the chest and knee joint. In particular, the fluorescence signal of P800SO3 was clearly observed in a section of the ribs, where it pointed out fractured bone fragments by tumor mass. Moreover, the P800SO3 signal from the left knee joint also showed a small bone fragment in the distal femur and was highlighted in the proximal tibia. Using targeted NIR fluorophores, metastatic bone tumors were monitored under the NIR fluorescence imaging system in real time, which enabled the in vivo diagnosis of bone metastasis by providing the location of the metastatic bone tumors.

Currently available chemotherapy is associated with serious side effects, and therefore novel drug delivery systems (DDSs) are required to specifically deliver anticancer drugs to targeted sites. In this study, we evaluated the feasibility of visible light-cured glycol chitosan (GC) hydrogels with controlled release of doxorubicin⋅hydrochloride (DOX⋅HCl) as local DDSs for effective cancer therapy in vivo. The storage modulus of the hydrogel precursor solutions was increased as a function of visible light irradiation time. In addition, the swelling ratio of the hydrogel irradiated for 10 s (GC

Photothermal therapy (PTT) using a near-infrared (NIR) heptamethine cyanine fluorophore has emerged as an alternative strategy for targeted cancer therapy. NIR fluorophores showing a high molar extinction coefficient and low fluorescence quantum yield have considerable potential applications in photothermal cancer therapy. In this study, a bifunctional sorbitol&ndash, ZW800 conjugate was used as an advanced concept of photothermal therapeutic agents for in vivo cancer imaging and therapy owing to the high tumor targetability of the sorbitol moiety and excellent photothermal property of NIR heptamethine cyanine fluorophore. The sorbitol&ndash, ZW800 showed an excellent photothermal effect increased by 58.7 &deg, C after NIR laser irradiation (1.1 W/cm2) for 5 min. The HT-29 tumors targeted by sorbitol&ndash, ZW800 showed a significant decrease in tumor volumes for 7 days after photothermal treatment. Therefore, combining the bifunctional sorbitol&ndash, ZW800 conjugate and NIR laser irradiation is an alternative way for targeted cancer therapy, and this approach holds great promise as a safe and highly efficient NIR photothermal agent for future clinical applications.

A facile, cost-effective and single-step pyrolysis approach using a single precursor is introduced to fabricate boron-doped carbon (BDC) without using a template, solvent, or catalyst. BDC has the ability to reduce oxygen directly to water with four electrons in an alkaline medium and exhibits excellent stability as well as resistance to methanol oxidation and CO poisoning. BDC is a promising alternative to conventional Pt-based catalysts as a metal-free catalyst for oxygen reduction reaction in alkaline fuel cells. Keywords: Boron-doped carbon, Electrocatalyst, Oxygen reduction, Alkaline fuel cells, Non-precious catalyst

The glucan that was produced by glucosyltransferases (GTFs) from Streptococcus mutans was examined for its stimulating functions toward murine peritoneal macrophages. Soluble glucan was obtained by the reaction with cell-free crude GTFs and sucrose, followed by ethanol precipitation, dispersion in water and re-precipitation by ethanol. Soluble glucan, those average molecular weight was about 3 x 10(5), was composed of mixture of alpha-1,6 and alpha-1,3 linkages in a 3:1 ratio. When 30 and 60 microg/ml of the glucan was incubated with peritoneal macrophages, the lysosomal phosphatase activity was increased in a dose-dependent manner, indicating that soluble glucan may activate macrophages. To examine its effects on the various functions of macrophages, soluble glucan was orally administered daily at a level of 100 mg/kg of body weight to C57BL/6 mice. Significant stimulation of the production of H2O2 by the macrophages was observed without any increase in NO production. The production of tumor necrosis factor-alpha (TNF-alpha) by the macrophages was also stimulated from 538.73-555.06 pg/ml to 585.73-596.40 pg/ml during 15 days of oral administration of soluble glucan. The cytotoxicity of peritoneal macrophages against B16 tumor cells was significantly enhanced by 25-38% during 15 days of oral administration. These results may indicate that soluble glucan stimulates the immune functions of macrophages.

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