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Till date, different types of conventional drugs have been used to fight tumors. However, they have significant flaws, including their usage being constrained because of their low bioavailability, poor supply, and serious side effects. The modern combination therapy has been viewed as a potent strategy for treating serious illnesses, including cancer-type feared diseases. The nanoparticles are a promising choice for cancer therapeutic and diagnostic applications because of their fascinating optoelectronic and physicochemical features. Among the metallic nanoparticles, Zinc oxide nanoparticles possess interesting physicochemical and anti-cancer characteristics, such as ROS generation, high retention, enhanced permeability etc., making them attractive candidates for the treatment and diagnosis of cancer. Zinc oxide nanoparticles showed anti-cancer property via excessive reactive oxygen species (ROS) production, and by the destruction of mitochondrial membrane. Here, we have synthesized organic/inorganic hybrid nanosystem composed of chymotrypsin protein (Chymo) with AzureC (AzC) conjugated with Zinc oxide nanoparticles (ZnONPs). The conjugation of AzureC with ZnONPs was confirmed by transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) experiment. The interaction of Chymo with AzC alone and AzC-ZnONPs was investigated, and it was observed that the interaction was enhanced in the presence of ZnONPs, which was concluded by the results obtained from different spectroscopic techniques such as UV-Visible spectroscopy, fluorescence spectroscopy and circular dichroism in combination with molecular docking. UV-Visible spectroscopic studies and the corresponding binding parameters showed that the binding of AzC-ZnONPs complex with Chymo is much higher than that of AzC alone. Moreover, the fluorescence measurement showed enhancement in static quenching during titration of Chymo with AzC-ZnONPs as compared to dye alone. In addition to this, circular dichroism results show that the dye and dye-NPs conjugate do not cause much structural change in α-Chymo. The molecular docking and thermodynamic studies showed the predominance of hydrogen bonding, Van der Waal force, and hydrophobic forces during the interactions. After correlation of all the data, interaction of Chymo with AzC-ZnONPs complex showed strong interaction as compared to dye alone. The moderate binding with chymo without any alteration in the structure makes it desirable for the distribution and pharmacokinetics. In addition, the in vitro cytotoxicity of the AzC-ZnONPs was demonstrated on A-549 adenocarcinoma cell line. Our findings from physiochemical investigations suggested that the chymotrypsin coated AzC conjugated ZnONPs could be used as the novel nanoconjugates for various cancer phototherapies. [ABSTRACT FROM AUTHOR]

The present study provides design guidance for unique multipotent molecules that sense and generate singlet oxygen (1O2). A rhodamine 6G‐aminomethylanthracene‐linked donor‐acceptor molecule (RA) is designed and synthesized for demonstrating wavelength‐dependent functionalities as follows; (i) RA acts as a conventional fluorogenic 1O2 sensor molecule like the commercially available reagent, singlet oxygen sensor green (SOSG), when it absorbs ultraviolet (UV)‐visible light and reacts with 1O2. (ii) RA acts as a temporally controlled 1O2 sensing reagent under the longer wavelength (∼700 nm) photosensitization. RA enters an intermediate state after capturing 1O2 and does not become strongly fluorescent until it is exposed to UV, blue, or green light. (iii) RA acts as an efficient photosensitizer to generate 1O2 under green light illumination. The spin‐orbit charge transfer mediated intersystem crossing (SOCT‐ISC) process achieves this function, and RA shows a potential cancer‐killing effect on pancreatic cancer cells. The wavelength‐switchable functionalities in RA offer to promise molecular tools to apply 1O2 in a spatiotemporal manner. [ABSTRACT FROM AUTHOR]

This review explores the potential of covalent organic frameworks in advancing cancer phototherapy, specifically in photothermal and photodynamic therapy, as well as their contributions to combination phototherapies. It also underlines the need for standardized protocols to facilitate their integration into clinical settings. [Display omitted] • COFs demonstrate precise and targeted action in cancer phototherapy. • Their ability to generate reactive oxygen species marks a significant advancement. • Combination therapies involving COFs exhibit promising synergistic effects in phototherapy. • Rigorous evaluation, in vivo stability assessment, and innovative drug delivery strategies are essential for successful phototherapy translation. The global prevalence of cancer presents a formidable challenge to medical systems, compelling the pursuit of novel and effective therapeutic modalities to improve patient survival rates. In this context, cancer phototherapy, encompassing both photodynamic (PDT) and photothermal (PTT) therapies, stands out as a targeted, minimally invasive modality to trigger the selective ablation of cancer cells. Covalent organic frameworks (COFs), with their distinct crystalline and porous nature, excellent biocompatibility, and chemical robustness, are increasingly recognized as outstanding materials to propel cancer phototherapy forward. In this review, we focus on examining the application of COF nanoparticles in the domain of PDT and PTT, demonstrating their potent anti-cancer capabilities. We pay special attention to combination therapies that exploit COFs, particularly those that elicit immunogenic cell death. These synergistic approaches offer considerable promise for the enhancement of cancer therapy efficiency. Additionally, we address the prevalent hurdles associated with COF-based cancer phototherapy, such as toxicity concerns, in vivo stability issues, and the complexities of photo agent delivery. We also discuss potential methods to overcome these barriers, especially through surface modifications of COFs. The review concludes by charting prospective research paths and the urgent need for the establishment of standardized procedures to fast-track the clinical adoption of COF-based phototherapy. By offering a detailed yet succinct outline of the capabilities of COFs in advancing cancer phototherapy, this article provides valuable insights for investigators in this vibrant field. [ABSTRACT FROM AUTHOR]

The constant evolution and advancement of the biomedical field requires robust and innovative research. Two-dimensional nanomaterials are an emerging class of materials that have risen the attention of the scientific community. Their unique properties, such as high surface-to-volume ratio, easy functionalization, photothermal conversion, among others, make them highly versatile for a plethora of applications ranging from energy storage, optoelectronics, to biomedical applications. Recent works have proven the efficiency of 2D nanomaterials for cancer photothermal therapy (PTT), drug delivery, tissue engineering, and biosensing. Combining these materials with hydrogels and scaffolds can enhance their biocompatibility and improve treatment for a variety of diseases/injuries. However, given that the use of two-dimensional nanomaterials-based polymeric composites for biomedical applications is a very recent subject, there is a lot of scattered information. Hence, this review gathers the most recent works employing these polymeric composites for biomedical applications, providing the reader with a general overview of their potential. [ABSTRACT FROM AUTHOR]

This review highlights organic molecule-based optical agents as phototheranostic agents and developments of organic molecule-based phototheranostic agents for enhanced cancer therapy. [Display omitted] • General mechanisms and significance of cancer phototherapy. • The unique merits of organic molecules as phototheranostic agents over polymer agents and inorganic materials. • Recent developments, perspectives, and challenges of organic molecule-based phototheranostic agents for enhanced cancer phototherapy are discussed. Phototherapy, includes photodynamic therapy (PDT) and photothermal therapy (PTT), which combine light with an adequate wavelength and a chemical phototheranostic agent in the absence or presence of oxygen, possesses substantial potential for cancer treatment due to its significant specificity, extremely low invasiveness, flexible administration, and effective cancer therapy. In recent years, organic molecules have engaged extensive attention as potential optical agents for phototherapy because of their definite molecular structure, synthetic flexibility, tailored photophysical properties, and excellent biocompatibility and biodegradability. In this review, we address current research advances in organic molecule-based phototheranostic agents and discuss the strategies to enhance phototherapy. Current bottlenecks and future perspectives of next-generation organic molecule-based phototheranostic agents for amplified phototherapy are also itemized and discussed. [ABSTRACT FROM AUTHOR]

Till date, different types of conventional drugs have been used to fight tumors. However, they have significant flaws, including their usage being constrained because of their low bioavailability, poor supply, and serious side effects. The modern combination therapy has been viewed as a potent strategy for treating serious illnesses, including cancer-type feared diseases. The nanoparticles are a promising choice for cancer therapeutic and diagnostic applications because of their fascinating optoelectronic and physicochemical features. Among the metallic nanoparticles, Zinc oxide nanoparticles possess interesting physicochemical and anti-cancer characteristics, such as ROS generation, high retention, enhanced permeability etc., making them attractive candidates for the treatment and diagnosis of cancer. Zinc oxide nanoparticles showed anti-cancer property via excessive reactive oxygen species (ROS) production, and by the destruction of mitochondrial membrane. Here, we have synthesized organic/inorganic hybrid nanosystem composed of chymotrypsin protein (Chymo) with AzureC (AzC) conjugated with Zinc oxide nanoparticles (ZnONPs). The conjugation of AzureC with ZnONPs was confirmed by transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) experiment. The interaction of Chymo with AzC alone and AzC-ZnONPs was investigated, and it was observed that the interaction was enhanced in the presence of ZnONPs, which was concluded by the results obtained from different spectroscopic techniques such as UV-Visible spectroscopy, fluorescence spectroscopy and circular dichroism in combination with molecular docking. UV-Visible spectroscopic studies and the corresponding binding parameters showed that the binding of AzC-ZnONPs complex with Chymo is much higher than that of AzC alone. Moreover, the fluorescence measurement showed enhancement in static quenching during titration of Chymo with AzC-ZnONPs as compared to dye alone. In addition to this, circular dichroism results show that the dye and dye-NPs conjugate do not cause much structural change in α-Chymo. The molecular docking and thermodynamic studies showed the predominance of hydrogen bonding, Van der Waal force, and hydrophobic forces during the interactions. After correlation of all the data, interaction of Chymo with AzC-ZnONPs complex showed strong interaction as compared to dye alone. The moderate binding with chymo without any alteration in the structure makes it desirable for the distribution and pharmacokinetics. In addition, the in vitro cytotoxicity of the AzC-ZnONPs was demonstrated on A-549 adenocarcinoma cell line. Our findings from physiochemical investigations suggested that the chymotrypsin coated AzC conjugated ZnONPs could be used as the novel nanoconjugates for various cancer phototherapies.

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 (808 nm, 330 mW cm -2 , and 3 min). This work provides a valuable guideline for rational design of PTAs for cancer phototherapy., (© 2024 Wiley‐VCH GmbH.)

Cancer phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has been extensively studied in recent years because of its noninvasive properties, high efficiency, improved selectivity, and reduced side effects. Gold nanoclusters (AuNCs) have the advantages of high biocompatibility, high biosafety, excellent photoresponse, and high tumor penetration ability. This review analyzes the use of AuNCs in tumor phototherapy in recent years from three aspects, namely, AuNCs in PDT, AuNCs in PTT, and AuNCs in combination therapy, and presents the high potential of AuNCs in cancer phototherapy. This review aims to provide readers with the unique advantages, diversified application approaches, and bright application prospects of AuNCs in phototherapy and to provide insights into strategies for applying AuNCs to tumor phototherapy.

Nanomaterials-based phototherapies, mainly including photothermal therapy (PTT), photodynamic therapy (PDT) and photoimmunotherapy (PIT), present high efficacy, minimal invasion and negligible adverse effects in cancer treatment. The integrated phototherapeutic modalities can enhance the efficiency of cancer immunotherapy for clinical application transformation. The near-infrared (NIR) light source enables phototherapies with the high penetration depth in the biological tissues, less toxic to normal cells and tissues and a low dose of light irradiation. Mediated via the novel NIR-responsive nanomaterials, PTT and PDT are able to provoke cancer cells apoptosis from the generated heat and reactive oxygen species, respectively. The released cancer-specific antigens and membrane damage danger signals from the damaged cancer cells trigger immune responses, which would enhance the antitumor efficacy via a variety of immunotherapy. This review summarized the recent advances in NIR-triggered photo-/immune-therapeutic modalities and their synergistic mechanisms and applications toward cancers. Furthermore, the challenges, potential solutions and future directions of NIR-triggered photo-/immunotherapy were briefly discussed.

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is regarded as a more effective method for cancer treatment than single PDT or PTT. However, development of single component and near‐infrared (NIR) triggered agents for efficient dual phototherapy remains a challenge. Herein, a simple strategy to develop dual‐functional small‐molecules‐based photosensitizers for combined PDT and PTT treatment is proposed through: 1) finely modulating HOMO–LUMO energy levels to regulate the intersystem crossing (ISC) process for effective singlet oxygen (1O2) generation for PDT; 2) effectively inhibiting fluorescence via strong intramolecular charge transfer (ICT) to maximize the conversion of photo energy to heat for PTT or ISC process for PDT. An acceptor–donor–acceptor (A‐D‐A) structured small molecule (CPDT) is designed and synthesized. The biocompatible nanoparticles, FA‐CNPs, prepared by encapsulating CPDT directly with a folate functionalized amphipathic copolymer, present strong NIR absorption, robust photostability, cancer cell targeting, high photothermal conversion efficiency as well as efficient 1O2 generation under single 808 nm laser irradiation. Furthermore, synergistic PDT and PTT effects of FA‐CNPs in vivo are demonstrated by significant inhibition of tumor growth. The proposed strategy may provide a new approach to reasonably design and develop safe and efficient photosensitizers for dual phototherapy against cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Research has shown that the pregnancies of children who later developed cancer have a higher incidence of complications including some that may also increase the likelihood of hyperbilirubinemia and need for phototherapy. Also, after Auger's approach, we restricted analyses to children whose cancer diagnosis occurred at least 2 months after the first diagnosis of hyperbilirubinemia or procedure code for phototherapy. Risk for cancer among children born between 1977 and 2013 who were either diagnosed with neonatal jaundice or hyperbilirubinemia or who were treated with phototherapy, limiting to cancer cases diagnosed between ages 4-11 (n = 2,013 cases, 195,877 controls). [Extracted from the article]

Advanced colorectal cancer has a high mortality rate since conventional treatments have limited therapeutic effects and poor prognosis with high risks of metastasis and recurrence. Photodynamic therapy (PDT) is a promising treatment modality for the eradication of colorectal cancer, but its curative efficacy is severely affected by tumor hypoxia. Herein, we developed a core-shell gold nanocage coated with manganese dioxide and hyaluronic acid (AMH) for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic phototherapy in situ. The AMH nanoparticles can generate abundant oxygen from mild acidic/H 2 O 2 medium, which can further enhance the PDT efficacy of AMH itself under near infrared (NIR) irradiation. Meanwhile, AMH-based PDT induced immunogenic cell death (ICD) of tumor cells with damage-associated molecular patterns (DAMPs) release and facilitated the dendritic cells (DCs) maturation to further potentiate the systematic antitumor immunity against advanced tumors. In vivo experiment results exhibited that AMH nanoparticles not only had the ability of targeting tumor but also in situ produced sufficient oxygen to relieve the tumor hypoxia. Furthermore, AMH-mediated oxygen-boosted immunogenic PDT effectively inhibited the tumor growth and recurrence. Thus, this work provides a potent targeted delivery nanoplatform for enhanced immunogenic PDT against advanced cancers. Local hypoxic tumor microenvironment not only greatly limits the photodynamic therapy (PDT) efficacy, but also has an association with tumor invasiveness and metastasis. This study provides an AMH nanoparticle for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic PDT in situ. AMH nanoparticle exhibits a good tumor-targeted ability to in situ produce abundant oxygen to relieve the tumor hypoxia, and initiates the potent oxygen-boosted immunogenic PDT effect under NIR irradiation to effectively inhibit the growth and recurrence of colorectal tumor. This oxygen-boosted immunogenic PDT nanosystem can be a promising candidate for advanced tumor treatment. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Black phosphorus nanosheets (BP NSs), a kind of attractive two-dimensional materials, have been widely used in optoelectronics, transistors and photocatalysis. Recently, growing interest has been attracted to explore the application of BP NSs for cancer therapy in view of their unique properties. BP NSs have high surface area and negative charge, which can load drug, targeting molecules, photosensitizer, magnetic nanoparticles etc. They are also potential candidates for cancer phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) by virtue of extensive near-infrared absorbance. Furthermore, BP NSs exhibit biodegradable and compatible nature to avoid toxicity in vivo. In this review, the preparation and properties of BP NSs are firstly summarized. More importantly, multifunctional platform based on BP NSs for cancer therapy such as photothermal therapy, photodynamic therapy, chemotherapy, antibacterial therapy, chemo−/photothermal combined therapy, photothermal/gene- combined therapy, chemo−/photothermal/gene- combined therapy and chemo−/photothermal/photodynamic combined therapy is reviewed in detail. And the future perspectives of BP NSs is finally discussed. Unlabelled Image • We reviewed functional black phosphorus nanosheets for cancer therapy. • The exfoliation methods and properties of black phosphorus nanosheets were introduced. • The different kinds of delivery systems based on black phosphorus nanosheets for cancer therapy were reviewed in detail. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a method of the treatment of localized cancers, based on a photochemical reaction between a light-activated molecule or photosensitizer (PS), light, and molecular oxygen. Correct choice of PS is of fundamental importance for PDT efficacy. Despite numerous studies in this field, most known PS have some drawbacks, e.g. lack of specificity and aggregation in aqueous media. Consequently, the search for an ideal PS is essential for further development of PDT. Here we review classification and analyse main features of different generations of PS and describe the mechanisms of their action. Various methods of targeted delivery of PS to tumor cells are discussed. The advantages of PS nanoparticles with the effect of aggregation-induced emission (AIE) over the classic photosensitizers are presented. A possibility of practical application of such light-emitting structures in cancer phototherapy is shown. Photodynamic therapy (PDT) is a method of the treatment of localized cancers, based on a photochemical reaction between a light-activated molecule or photosensitizer (PS), light, and molecular oxygen. Correct choice of PS is of fundamental importance for PDT efficacy. Despite numerous studies in this field, most known PS have some drawbacks, e.g. lack of specificity and aggregation in aqueous media. Consequently, the search for an ideal PS is essential for further development of PDT. Here we review classification and analyse main features of different generations of PS and describe the mechanisms of their action. Various methods of targeted delivery of PS to tumor cells are discussed. The advantages of PS nanoparticles with the effect of aggregation-induced emission (AIE) over the classic photosensitizers are presented. A possibility of practical application of such light-emitting structures in cancer phototherapy is shown. [ABSTRACT FROM AUTHOR]

Photodynamic therapy is a clinically approved treatment approach for cancer. However, it has limited applications owing to poor water solubility and the short wavelength absorption of the photosensitizer (PS). We selected a near-infrared photosensitizer, SiNC, and encapsulated into a gold nanocage (AuNC) in the presence of phase-changing material. Then, the PS-encapsulated nanocage was coated with glycol chitosan (GC) with a cleavable peptide linkage or stable cysteine linkage to protect the PS from premature release and to improve the biocompatibility of the nanocage. We obtained particles of GC-coated SiNC-encapsulated AuNC with a neutral surface charge and approximately 160 nm in size. The enzyme-cleavable peptide-linked GC formulation (GC-pep@SiNC-AuNC) showed stronger phototoxicity and tumor suppression efficacy in a glioblastoma model compared with free NIR-PS and stable cysteine-linked GC-AuNC (GC-cys@SiNC-AuNC). This polymer-coated SiNC-AuNC may be a promising agent for brain cancer phototherapy. Near infrared photosensitizer-encapsulated gold nanocage was prepared and coated with glycol chitosan with stimuli-responsive or stable peptide linkage. The nanoformulation was found to have around 120-160 nm in size and neutral surface charge. In vitro and in vivo study in brain tumor showed that this formulation has a great combined phototherapy activity. Unlabelled Image [ABSTRACT FROM AUTHOR]

Although cyclometalated IrIII complexes have emerged as promising photosensitizers for photodynamic therapy, some key drawbacks still hamper clinical translation, such as operability in the phototherapeutic window and reactive oxygen species (ROS) production efficiency and selectivity. In this work, a cyclometalated IrIII complex conjugated to a far‐red‐emitting coumarin, IrIII–COUPY, is reported with highly favourable properties for cancer phototherapy. IrIII–COUPY was efficiently taken up by HeLa cells and showed no dark cytotoxicity and impressive photocytotoxicity indexes after irradiation with green and blue light, even under hypoxia. Importantly, a clear correlation between cell death and intracellular generation of superoxide anion radicals after visible light irradiation was demonstrated. This strategy opens the door to novel fluorescent photodynamic therapy agents with promising applications in theragnosis. [ABSTRACT FROM AUTHOR]

To improve the efficacy of traditional chemotherapy and radiotherapy and reduce their serious side effects, further efforts need to be exerted to identify better cancer therapeutic options that are effective, affordable, and acceptable to patients. In this study, a novel theranostic agent was produced to perform synergetic cancer immunotherapy and phototherapy. The theranostic agent, named natural killer (NK) cells carrying indocyanine green loaded liposomes was synthesized NK cells with ICG nanoparticles to serve as the agent for a newly-established cancer treatment. It is expected that the developed synergistic therapy can pave a new avenue for improved efficacy of cancer theranostics. [ABSTRACT FROM AUTHOR]

Abstract Photothermal therapy (PTT) has shown significant potential for anti-cancer modality. In this report, according to our best knowledge, we explore for the first time Ti 2 C-based MXene as a novel, highly efficient and selective agent for photothermal therapy (PTT). Ti 2 C superficially modified with PEG was obtained from the layered, commercially available Ti 2 AlC MAX phase in the process of etching aluminum layers using concentrated HF, and characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HREM) as well as X-ray photoelectron spectroscopy for chemical analysis (ESCA-XPS). The PEG-coated Ti 2 C flakes showed a satisfactory photothermal conversion efficacy (PTCE) and good biocompatibility in wide range of the tested concentrations. Through in vitro studies, the PEG-modified Ti 2 C demonstrated notable NIR-induced ability to cancerous cells' ablation with minimal impact on non-malignant cells up to the concentration of 37.5 μg mL−1. The applied doses of Ti 2 C_PEG in our work were even 24 times lower comparing other MXene-based photothermal agents. This work is expected to expand the utility of 2D MXenes to biomedical applications through the development of entirely novel agents for photothermal therapy. This work is expected to expand the utility of 2D MXenes to biomedical applications through the development of entirely novel agents for photothermal therapy. Graphical abstract Unlabelled Image Highlights • Ti 2 C MXene superficially modified with PEG was obtained and characterized. • The PEG-coated Ti 2 C showed a satisfactory photothermal conversion efficacy (PTCE). • The tested material is biocompatible in wide range of the tested concentrations. • The PEG-modified Ti 2 C demonstrated notable NIR-induced ability to cancerous cells' ablation. • The MXenes' influence on non-malignant cells up to the concentration of 37.5 μg mL–1 was minimal. [ABSTRACT FROM AUTHOR]

Abstract Photodynamic therapy is amongst the most rapidly developing therapeutic strategies against cancer. However, most photosensitizers are administered intravenously with very few reports about pulmonary applications. To address this issue, an inhalable formulation consisting of nanoparticles loaded with photosensitizer (i.e. curcumin) was developed. The nanoparticles were prepared using nanoprecipitation method. Dynamic light scattering measurements of the curcumin loaded nanoparticles revealed a hydrodynamic diameter of 181.20 ± 11.52 nm. In vitro irradiation experiments with human lung epithelial carcinoma cells (A549) showed a selective cellular toxicity of the nanoparticles upon activation using LED irradiating device. Moreover, curcumin nanoparticles exhibited a dose-dependent photocytotoxicity and the IC 50 values of curcumin were directly dependent on the radiation fluence used. The nanoparticles were subsequently spray dried using mannitol as a stabilizer to produce Nano-in-Microparticles with appropriate aerodynamic properties for a sufficient deposition in the lungs. This was confirmed using the next generation impactor, which revealed a large fine particle fraction (64.94 ± 3.47%) and a mass median aerodynamic diameter of 3.02 ± 0.07 μm. Nano-in-Microparticles exhibited a good redispersibility and disintegrated into the original nanoparticles upon redispersion in aqueous medium. The Langmuir monolayer experiments revealed an excellent compatibility of the nanoparticles with the lung surfactant. Results from this study showed that the Nano-in-Microparticles are promising drug carriers for the photodynamic therapy of lung cancer. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract IR780 is a near infrared (NIR) dye with a huge potential to be applied in cancer phototherapy and imaging. However, IR780 poor water solubility and acute cytotoxicity limit its direct use in cancer theragnostic. Herein, a novel Hyaluronic acid (HA)-based amphiphilic polymer was used, for the first time, in the preparation of polymeric nanoparticles (HPN) encapsulating IR780 aimed to be applied in breast cancer therapy. Furthermore, HPN co-encapsulating IR780 and Doxorubicin (DOX) were also produced in order to further enhance the therapeutic effectiveness of this nanoformulation. The results revealed that HPN were able to successfully encapsulate IR780 (IR-HPN) and the IR780-DOX combination (IR/DOX-HPN). Furthermore, the encapsulation of IR780 in HPN improved its absorption at 808 nm by about 2.2-fold, thereby enhancing its photothermal potential, as well as its cytocompatibility. The 2D in vitro cell uptake studies demonstrated that the nanostructures displayed a higher internalization by breast cancer cells than by normal cells. In addition, the assays performed in 3D in vitro models of breast cancer revealed that HPN can penetrate into spheroids. Furthermore, the 3D in vitro studies also demonstrated that the combined application of IR-HPN and NIR light was unable to induce cytotoxicity on spheroids. In contrast, IR/DOX-HPN produced a decrease on spheroids cells' viability, and their combination with NIR light induced an even stronger therapeutic effect, thus revealing the potential of these nanoparticles for cancer chemo-phototherapy. [ABSTRACT FROM AUTHOR]

Abstract Ru(II) compounds are potential candidates for photodynamic therapy (PDT) and auxiliary ligands may have an impact on the property of the resulting coordination compounds. In the present study, two Ru(II) compounds based on 5-(2-pyrazinyl)tetrazole (Hpztz) and two classic auxiliary ligands, 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) have been prepared and characterized, namely [Ru(pztz)(bipy) 2 ][PF 6 ] (1) and [Ru(pztz)(phen) 2 ][PF 6 ] (2). The nanoparticles (NPs) of the two compounds have been prepared by self-assembly in aqueous solution. In vitro MTT assay on HeLa cells show that [Ru(pztz)(phen) 2 ][PF 6 ] with a lower IC 50 (half-maximal inhibitory concentration) of only 7.4 μg/mL is superior to that of [Ru(pztz)(bipy) 2 ][PF 6 ] (17.8 μg/mL) under irradiation. Meanwhile, negligible dark toxicity have been also observed for the two compounds. In addition, in vivo fluorescence imaging suggests that [Ru(pztz)(phen) 2 ][PF 6 ] NPs are able to target to the tumor by enhanced permeability and retention effect (EPR). Furthermore, in vivo phototherapy on nude mice demonstrate that such NPs can effectively inhibit the growth of the tumor. After treatment for 10 cycles, an obvious decrease in the tumor volume can be observed while the normal tissues, including heart, liver, spleen, lung and kidney, suffer from no damage, indicating the high phototoxicity, low dark toxicity and excellent biocompatibility of [Ru(pztz)(phen) 2 ][PF 6 ] NPs. Graphical abstract [Ru(pztz)(phen) 2 ][PF 6 ] can be used as potential candidate for photodynamic therapy (pztz = (5-(2-pyrazinyl)tetrazole, bipy = 2,2′-bipyridine). Unlabelled Image Highlights • 5-(2-pyrazinyl)tetrazole (Hpztz) was prepared. • 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) were used. • [Ru(pztz)(bipy) 2 ][PF 6 ] (1) and [Ru(pztz)(phen) 2 ][PF 6 ] (2) were prepared. • Compound 2 is superior to 1 in terms of cytotoxicity. • [Ru(pztz)(phen) 2 ][PF 6 ] can be used for photodynamic therapy in vivo. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • CX-NPs were synthesized and characterized by electron microscopy. • Temperature increment of CX-NPs under 808-nm laser light was determined. • C540 (B16/F10) cell toxicity of CX-NPs was evaluated. • CX-NPs photothermally inhibited tumor growth. Abstract Nanosized carbonaceous materials are favorable in biomedicine applications including photothermal therapy (PTT) of cancer. Since conventional strategies of cancer treatment have not responded to this serious disease, development of efficient alternative and promising strategies is highly desirable. In this study, carbon xerogel nanoparticles (CX-NPs) were synthesized as a novel photothermal nanomaterial and activated upon laser light of 808-nm wavelength for cancer phototherapy application. The synthesized CX-NPs had a spherical shape with a size of about 16 nm that showed nice photothermal conversion ability. Upon light irradiation with a power density of 1.0 W cm−2 for 15 min, a temperature increment occurred. A concentration-dependent cytotoxicity was also obtained for CX-NPs toward the C540 (B16/F10) cell line upon light irradiation, while CX-NPs presented biocompatibility in the mice model in dark. Photothermal property of CX-NPs efficiently led to reduction in the cell viability. A low-dose of CX-NPs was also applied in PTT of a melanoma tumor-bearing animal model. Based on tumor histopathological evaluations and volume change measurements in mice, a very good control of tumor situations after PTT by CX-NPs was attained. The findings revealed that CX-NPs is a good and novel photoabsorber for PTT of cancer. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials have received great attention from the scientific community over the past few decades because of their unique physical and chemical properties. In this minireview, we will summarize the recent progress of the use of various carbon nanomaterials in the field of cancer phototherapy. The structural characteristics of each category and the surface functionalization strategies of these nanomaterials will be briefly introduced before focusing on their therapeutic applications. Recent advances on their use in photothermal therapy, photodynamic therapy, and combined phototherapies are presented. Moreover, a few challenges and perspectives on the development of carbon nanomaterials for future theranostics are also discussed. The many dimensions of carbon nanomaterials: The recent progress of carbon nanomaterials in the field of cancer phototherapy is reviewed. A few challenges, perspectives on the development of carbon nanomaterials for future phototheranostics are also discussed. [ABSTRACT FROM AUTHOR]

Abstract Application of carbon nanomaterials to near-infrared light-mediated phototherapy has attracted great interest. However, their practical use in biological systems is severely limited by their poor water dispersibility, inevitable adsorption of plasma proteins, and their single therapeutic function. Herein, we prepared a phycocyanin (PC)-functionalized single-walled carbon nanohorns (PC@SWNHs) hybrid, where PC is used to preform a protein corona around the SWNHs through non-covalent interface interactions. In the PC@SWNHs, the preformed PC corona effectively improves the water dispersibility of the SWNHs and protects them from plasma protein adsorption. In addition, the excellent photodynamic activity of PC overcomes the inability of SWNHs to generate reactive oxygen species. The SWNHs not only give the hybrid a photothermal therapy (PTT) function, but they also enhance the photostability of PC. These characteristics of the PC@SWNHs are confirmed by in vitro and in vivo experiments, where synergistic photodynamic therapy (PDT)/PTT growth inhibition of tumors is achieved. The PC@SWNHs also act as a photoacoustic/thermal imaging agent to visualize the in vivo treatment process. Hence, this work not only paves the way to use the complementarity between SWNHs and proteins for multifunctional cancer theranostics, but it also allows for a better understanding of bio–nano interface interactions between them. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract Phototherapy has drawn increasing attention including the use of nanocarriers with high drug loading capacity and delivery efficacy for target-specific therapy. We have made use of naturally-occurring halloysite nanotubes (HNTs) to build a biomimetic nanocarrier platform for target-specific delivery of phototherapeutic agents. The HNTs were decorated with poly(sodium- p -styrenesulfonate) (PSS) to enhance the biocompatibility, and were further functionalized by lumen loading the type-II photosensitizer indocyanine green (ICG). The HNT-PSS-ICG nanocarrier, without further tethering targeting groups, was shown to associate with the membrane of giant unilamellar vesicles (GUVs) via Pickering effects. Application of HNT-PSS-ICG nanocarrier to human breast cancer cells gave rise to a cell mortality as high as 95%. The HNT-PSS-ICG nanocarrier was further coated with MDA-MB-436 cell membranes to endow it with targeting therapy performance against breast cancer, which was confirmed by in vivo experiments using breast cancer tumors in mice. The membrane-coated and biocompatible nanocarrier preferentially concentrated in the tumor tissue, and efficiently decreased the tumor volume by a combination of photodynamic and photothermal effects upon near-infrared light exposure. Our results demonstrate that the HNT-based nanocarrier by virtue of facial preparation and high loading capacity can be a promising candidate for membrane-targeting nanocarriers. Graphical abstract Biocompatible halloysite nanotube as target-specific nanocarrier for the application in phototherapy of breast cancer. Image 1 [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Green-reduction of GO with 3 mM of LAA during 60 min at 80 °C is optimal. • HA-based coating improves the stability and cytocompatibility of rGO. • HA-functionalized rGO has a higher uptake by breast cancer cells. • Photothermal effect mediated by HA-functionalized rGO induces cancer cells’ ablation. Abstract Reduced graphene oxide (rGO) nanomaterials display promising properties for application in cancer photothermal therapy (PTT). rGO is usually obtained by treating graphene oxide (GO) with hydrazine hydrate. However, this reducing agent contributes for the low cytocompatibility exhibited by rGO. Furthermore, rGO has a low water stability and does not show selectivity towards cancer cells. Herein, rGO attained using an environmentally-friendly method was functionalized with a novel hyaluronic acid (HA)-based amphiphilic polymer to be used in targeted cancer PTT. Initially, the green-reduction of GO with L-Ascorbic acid was optimized considering the near infrared absorption and the size distribution of the nanomaterials. Then, rGO was functionalized with the HA-based amphiphile. The functionalization of rGO improved its stability, cytocompatibility and internalization by CD44 overexpressing cells, which indicates the targeting capacity of this nanoformulation. Furthermore, the on-demand PTT mediated by HA-functionalized rGO induced cancer cells’ ablation, thereby confirming its potential for targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract To overcome irradiation-dependence of cancer phototherapy, a near infrared aza-BODIPY-based photothermogenic photosensitizer BDY with 2-Pyridone group has been synthesized for imaging-guided photothermal synergistic sustainable photodynamic therapy. Multifunctional water-soluble BDY nanoparticles (NPs), with high photothermal conversion efficiency of 35.7% and excellent singlet oxygen (1O 2) generation ability, are prepared by self-assembling. The reversible transformation between 2-pyridone moiety and its endoperoxide form endows BDY with continuous 1O 2 generation ability under illumination and non-illumination conditions. Simultaneously, BDY NPs exhibit excellent tumor targeting properties by enhanced permeability and retention (EPR) effect and photoacoustic imaging (PAI) ability. Furthermore, the photothermal assisted sustainable photodynamic therapy can significantly inhibit tumor growth (93.4% inhibition) with almost no side effects by intermittent laser illumination. The finding highlights that this photothermal synergistic sustainable phototherapy presents great potential for clinical applications. [ABSTRACT FROM AUTHOR]

Tumor hypoxia strikingly restricts photodynamic therapy (PDT) efficacy and limits its clinical applications in cancer therapy. The ideal strategy to address this issue is to develop oxygen-independent PDT systems. Herein, the rationally designed tumor pH-responsive polymeric micelles are devised to realize oxygen-independent combined PDT and photothermal therapy (PTT) under near-infrared light (NIR) irradiation. The triblock copolymer, poly(ethylene glycol)- b -poly(ε-caprolactone)- b -poly(2-(piperidin-1-yl)ethyl methacrylate) (PEG- b -PCL- b - PPEMA), was prepared to co-encapsulate cypate and singlet oxygen donor (diphenylanthracene endoperoxide, DPAE) via self-assembly to obtain the micellar delivery system (C/O@N-Micelle). C/O@N-Micelle showed remarkable tumor accumulation and improved cellular internalization (2.1 times) as the pH value was changed from 7.4 during blood circulation to 6.8 in tumor tissues. The micelles could produce a potent hyperthermia for PTT of cypate under 808 nm NIR irradiation, which simultaneously induced thermal cycloreversion of DPAE generating abundant singlet oxygen for PDT without participation of tumor oxygen. Finally, the photothermally triggered PDT and PTT combination achieved efficient tumor ablation without remarkable systemic toxicity in an oxygen-independent manner. This work represents an efficient strategy for oxygen-independent combined PDT and PTT of cancers under NIR irradiation through co -encapsulation of cypate and DPAE into tumor pH-responsive polymeric micelles. [ABSTRACT FROM AUTHOR]

Carbon dots (CDs) with unique optical properties are a stable and highly biocompatible fluorescent material offering enormous application potential in optical imaging and photothermal cancer therapy (PTT). However, the low photothermal conversion efficiency and the high power density still impede the development of CDs in PTT. Herein, the nitrogen and oxygen co-doped CDs (N-O-CDs) with strong absorbance in the near infrared (NIR) region were prepared from 1,3,6-trinitropyrene (TNP) and N-containing polymer of branched polyethylenimine (BPEI) via a one-step molecular fusion route. The as-prepared black N-O-CDs with high photostability and superb biocompatibility can be utilized not only as a new fluorescence imaging agent but also as an excellent PTT agent in vivo . The structure, optical properties, bioimaging, photothermal effect in vitro , and therapeutic efficiency in vivo of the N-O-CDs are investigated. The low power density (0.8 W cm −2 ) and high photothermal conversion efficiency (η = 38.3%) facilitate N-O-CDs to act as an ideal theranostic agent for fluorescence imaging and photothermal therapy in vitro and in vivo . This work highlights CDs as an excellent candidate for efficient cancer therapy. [ABSTRACT FROM AUTHOR]

We thank Heck I et al i . for their comment on our recent study of neonatal phototherapy and childhood cancer.[1] Heck I et al i . suggest that the association between phototherapy and the risk of childhood cancer may be explained by shared risk factors, such as preterm birth and low birth weight. The foremost problem is that the main exposure measure in Heck I et al i .'s analysis is a combination of phototherapy and untreated hyperbilirubinemia, rather than phototherapy specifically. It is also likely that the proportion of jaundiced newborns who received phototherapy differs in each gestational age or birth weight strata, although this is hard to verify from how Heck I et al i present their results. [Extracted from the article]

Photodynamic therapy of cancer comprises the activation of photosensitizer molecules delivered to cancer cells, to generate reactive oxygen species that mediate cytotoxicity. In this study, previously synthesized dendritic magnesium tribenzoporphyrazines were incorporated into four types of liposomes containing either 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC) or 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE) as the zwitterionic lipids. The addition of either l -α-phosphatidyl- dl -glycerol (PG) or 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) imparted a negative or positive charge, respectively. Novel formulations were tested in oral squamous cell carcinoma cell lines (CAL 27, HSC-3) as well as cervical adenocarcinoma cells (HeLa). Positively charged DOTAP:POPC liposomes were the most effective carriers for all tested tribenzoporphyrazines. Calculated IC 50 values for DOTAP:POPC liposomes indicated that the incorporation of tribenzoporphyrazines into these liposomes can improve photocytotoxicity up to 50-fold compared to the free forms of macrocycles. Oral cancer cells (CAL 27 and HSC-3) were more sensitive to liposomal photodynamic treatment than HeLa cells. [ABSTRACT FROM AUTHOR]

Chemotherapy is an important treatment for malignant tumors; however, its efficacy and clinical application are limited by its side effects and drug resistance properties. Chemotherapy and phototherapy exhibit synergistic anti-tumor effects. In the present study, a carboxylated poly(amido-amine) (PAMAM) with low cytotoxicity was synthesized as a delivery nanocarrier for loading chemotherapeutic drugs, temozolomide (TMZ), and fluorescent dye indocyanine green (ICG). Hyaluronic acid (HA), which targets the CD44-overexpressing cancer cells, was modified on the nanocarrier surface to enhance the selective killing of melanoma cells. Temperature effect and singlet oxygen production experiments showed that the ICG-loaded nanoparticles exhibited good capability to generate heat and singlet oxygen under near-infrared (NIR) light (808 nm) irradiation. In vivo imaging measurement confirmed that the ICG-encapsulated nanoparticle was delivered successfully and effectively accumulated in the tumor site. In vitro and in vivo experiments revealed that the joint application of TMZ- and ICG-loaded nanoparticle can kill melanoma cells and suppress growth after NIR light irradiation. Thus, HA-modified carboxylated PAMAM loaded with TMZ and ICG serves as a promising nanoplatform for melanoma treatment. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a less-invasive treatment for cancer through the administration of less-toxic porphyrins and visible-light irradiation. Photosensitized damage of biomacromolecules through singlet oxygen (1O2) generation induces cancer cell death. However, a large quantity of porphyrin photosensitizer is required, and the treatment effect is restricted under a hypoxic cellular condition. Here we report the phototoxic activity of P(V)porphyrins: dichloroP(V)tetrakis(4-methoxyphenyl)porphyrin (CLP(V)TMPP), dimethoxyP(V)tetrakis(4-methoxyphenyl)porphyrin (MEP(V)TMPP), and diethyleneglycoxyP(V)tetrakis(4-methoxyphenyl)porphyrin (EGP(V)TMPP). These P(V)porphyrins damaged the tryptophan residue of human serum albumin (HSA) under the irradiation of long-wavelength visible light (>630 nm). This protein photodamage was barely inhibited by sodium azide, a quencher of 1O2. Fluorescence lifetimes of P(V)porphyrins with or without HSA and their redox potentials supported the electron-transfer-mediated oxidation of protein. The photocytotoxicity of these P(V)porphyrins to HeLa cells was also demonstrated. CLP(V)TMPP did not exhibit photocytotoxicity to HaCaT, a cultured human skin cell, and MEP(V)TMPP and EGP(V)TMPP did; however, cellular DNA damage was barely observed. In addition, a significant PDT effect of these P(V) porphyrins on a mouse tumor model comparable with the traditional photosensitizer was also demonstrated. These findings suggest the cancer selectivity of these P(V)porphyrins and lower carcinogenic risk to normal cells. Electron-transfer-mediated oxidation of biomacromolecules by P(V)porphyrins using long-wavelength visible light should be advantageous for PDT of hypoxic tumor. [ABSTRACT FROM AUTHOR]

To develop a cancer targeting lactate attenuator in vivo for cancer phototherapy and inhibition of HIF-1, we report an aptamer modified photo-responsive nanoparticle (labeled as Mn-D@BPFe-A) for lactate oxidation and cancer phototherapy. Mn-D@BPFe-A was constructed by the assembly of functional complex with BSA, followed by surface metal coordination and the recognition of Fe 3+ with GAG containing sequence. Upon irradiation, Mn-D@BPFe-A NPs can oxidize water with the generation of OH, which convert lactate into pyruvate both in vitro and in vivo . Obviously, the Mn-D@BPFe-A exhibits a significant tumor ablation owing to the light driven oxidation of lactic acid and dysfunction of mitochondria. Importantly, it can decrease both the level of lactate in cancer tissues and the expression of HIF-1α and Glut-1 in HepG-2 cells. These results demonstrated that oxidation of lactate with dysfunction of mitochondria by nucleic acid-Fe 3+ modified nanoparticle is an effective strategy for the development of non-oxygen dependent photodynamic effect agents. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs)-based diagnosis and phototherapy are emerging as the cutting-edge technologies for detection and treatment of cancer but their applications are still limited since insufficient and heterogeneous NPs accumulation in cancer often causes recurrence. To overcome these limitations, multifunctional microbubbles (MBs) were constructed with 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindotricarbocyanine iodide (DiR) and porphyrin grafted lipid (PGL). Both DiR and PGL self-assembled as microbubbles, the as-designed PGL-DiR MBs possess remarkably high drug loading contents (5.8% PGL and 10.38% DiR) and stable co-delivery drug combinations. In vivo experiments showed PGL-DiR MBs could serve as an excellent ultrasound contrast agent to enhance ultrasound imaging greatly for identifying the location and size of the tumors. Upon exposure to ultrasound, in situ conversion of PGL-DiR MBs into nanoparticles resulted in a remarkable increase in fluorescence intensity (~5 folds) in tumor compared with PGL-DiR NPs, validating the enhanced tumor accumulation and cellular uptake of therapeutic agents. PGL-DiR MBs showed complete tumor ablation without recurrence in vivo, while PGL-DiR NPs showed only 72.6% tumor growth inhibition at the same dose. We believe that PGL-DiR MBs will soon reach their full potential as an important class of phototherapeutic formulations and will contribute to remarkable advances in cancer treatments. [ABSTRACT FROM AUTHOR]

Femtosecond time-resolved transient absorption spectroscopy experiments and density functional theory computations were done for a mechanistic investigation of 3- (1-phenylvinyl)phenol (1) and 3-hydroxybenzophenone (2) in selected solvents. Both compounds went through an intersystem crossing (ISC) to form the triplet excited states Tππ* and Tnπ* in acetonitrile but behave differently in neutral aqueous solutions, in which a triplet excited state proton transfer (ESPT) induced by the ISC process is also proposed for 2 but a singlet ESPT without ISC is proposed for 1, leading to the production of the triplet quinone methide (QM) and the singlet excited QM species respectively in these two systems. The triplet QM then underwent an ISC process to form an unstable ground state intermediate which soon returned to its starting material 2. However, the singlet excited state QM went through an internal conversion process to the ground state QM followed by the formation of its final product in an irreversible manner. These differences are thought to be derived from the slow vinyl C−C rotation and the moderate basicity of the vinyl C atom in 1 as compared with the fast C−O rotation and the greater basicity of the carbonyl O atom of 2 after photoexcitation. This can account for the experimental results in the literature that the aromatic vinyl compounds undergo efficient singlet excited state photochemical reactions while the aromatic carbonyl compounds prefer triplet photochemical reactions under aqueous conditions. These results have fundamental and significant implications for understanding of the ESPT reactivity in general, as well as for the design of molecules for efficient QM formation in aqueous media with potential applications in cancer phototherapy. [ABSTRACT FROM AUTHOR]

Background A promising strategy for cancer diagnosis and therapy is the development of an agent for multimodal imaging and treatment. In the present paper we report on two novel multifunctional agents prepared on the porphyrazine pigment platform using a gadolinium (III) cation chelated by red-fluorescent tetrapyrrole macrocycles (GdPz1 and GdPz2). Methods Spectral and magnetic properties of the compounds were analyzed. Monitoring of GdPz1 and GdPz2 accumulation in the murine colon carcinoma CT26 was performed in vivo using fluorescence imaging and MRI. The photobleaching of GdPz1 or GdPz2 and tumor growth rate after photodynamic therapy (PDT) were assessed. Results GdPz1 and GdPz2 demonstrated the selective accumulation in tumor that was indicated by higher fluorescence intensity in the tumor area in comparison with the normal tissues. The results of MRI in vivo showed that GdPz1 or GdPz2 provided significant contrast enhancement of the tumor in T1 MR images. PDT with GdPz2 resulted in ~ 20% decrease in fluorescence intensity of the compound and the inhibition of tumor growth. Conclusions We assessed the efficiency of two innovative Gd(III) cation-porphyrazine chelates as bimodal MR and fluorescent probes and photosensitizers for PDT and showed their potentials for tumor diagnostics and treatment. General significance Water-soluble structures simple in preparation and administration into the body represent special interest for theranostics of tumors. Novel porphyrazine macrocycles chelating a central gadolinium cation demonstrated a good prospect as effective multimodal agents, representing a new approach to MRI and fluorescence imaging guided PDT. [ABSTRACT FROM AUTHOR]

Background: The world widespread rise in cancer incidence has caused an increase in the demand for effective and safe materials for treatment. One of the most prevalent forms of treatment for cancer is photodynamic therapy (PDT), which is seen as an alternative to radiotherapy, as well as chemotherapy. In more recent years, researchers are exploring new nanotechnology-based strategies to improve the effectiveness of PDT. Objective: The objective of this review is to explore the current trends and research findings associated with PDT and the development of nanotechnology as treatment modality for cancer. Nanotechnology commonly deals with nanomaterials, which are well defined by their reduced size (which is <100 nm), allowing these small nanostructured particles to have unique physical, chemical, and biological properties. The unique properties of nanomaterials attribute them to have enormous potential application in many interdisciplinary fields such as medicine, electronics, biomaterials, and so on. This mini-review presents a collection of important works published with focus of nanotechnology and cancer treatment by PDT. Conclusions: Despite significant efforts to develop nanosystems for efficient PDT cancer treatment, it remains a challenge to develop nanostructured drug delivery systems that combine targeted tumor recognition with effective production of reactive singlet oxygen under PDT irradiation. [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) absorbing nanoagents with functions of photoacoustic imaging (PAI) and photothermal therapy (PTT) have received great attention for cancer therapy. However, endowing them with multifunctions, especially targeting ability, for enhancing in vivo PAI/PTT generally suffers from the problems of synthetic complexity and low surface density of function groups. We herein report high density glycopolymers coated perylenediimide nanoparticles (PLAC-PDI NPs), self-assembled by poly(lactose)-modified perylenediimide (PLAC-PDI), as tumor-targeted PAI/PTT nanoagents. Atom transfer radical polymerization and click reaction were used in sequence to prepare PLAC-PDI, which can accurately control the content of poly(lactose) (PLAC) in PLAC-PDI and endow PLAC-PDI NPs with high density PLAC surface. The high density PLAC surface provided NPs with long-time colloidal stability, outstanding stability in serum and light, and specific targeting ability to cancer cells and tumors. Meanwhile, PLAC-PDI NPs also presented high photothermal conversion efficiency of 42% by virtue of strong p-p interactions among perylenediimide molecules. In living mice, PAI experiments revealed that PLAC-PDI NPs exhibited effective targeting ability and enhanced PTT efficacy to HepG2 tumor compared with control groups, lactose blocking, and ASGP-R negative tumor groups. Overall, our work provids new insights for designing glycopolymers-based therapeutic nanoagents for efficient tumor imaging and antitumor therapy. [ABSTRACT FROM AUTHOR]

Polymeric micelles loaded with multiple therapeutic modalities are important to overcome challenges such as drug resistance and improve the therapeutic efficacy. Here we report a new polymer micellar drug carrier that integrates chemotherapy and photothermal therapy in a single platform. Specifically, a narrow bandgap poly(dithienyl-diketopyrrolopyrrole) (PDPP) polymer was encapsulated together with a model anticancer drug doxorubicin (DOX) in the hydrophobic cores of polymeric micelles formed by Pluronic F127, an amphiphilic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. The PDPP polymer served as an organic photothermal agent that absorbs near-infrared light (700–1000 nm) and transforms into heat efficiently. The dual functional micelles co-loaded with PDPP and DOX in the hydrophobic compartment showed good colloidal stability after being stored at 4 °C at least over two months, and remained visibly stable after 808-nm laser irradiation. The loaded DOX had negligible effect on the size and photothermal property of the micelles. The release of DOX from the micelles could be enhanced by the “breathing” effect of shrinking/swelling of the micelles induced by the temperature change, owing to the thermosensitive nature of the F127 polymers. Importantly, the ternary F127/PDPP/DOX micelles under 808-nm laser irradiation showed enhanced cytotoxicity against cancer cells such as HeLa cells, compared to F127 micelles containing single modality of either PDPP or DOX only. [ABSTRACT FROM AUTHOR]

Photoimmunotherapy (PIT) is an emerging low side effect cancer therapy based on a monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye IRDye 700DX. IR700 is fluorescent, can be used as an imaging agent, and also is phototoxic. It induces rapid cell death after exposure to NIR light. PIT induces highly selective cancer cell death, while leaving most of tumor blood vessels unharmed, leading to an effect called super-enhanced permeability and retention (SUPR). SUPR significantly improves the effectiveness of the anticancer drug. Currently, the therapeutic effects of PIT are monitored using the IR700 fluorescent signal based on macroscopic fluorescence reflectance imagery. This technique, however, lacks the resolution and depth information to reveal the intratumor heterogeneity of mAb-IR700 distribution. We applied a minimally invasive two-channel fluorescence fiber imaging system by combining the traditional fluorescence imaging microscope with two imaging fiber bundles (~ 0.85 mm). This method monitored mAb-IR700 distribution and therapeutic effects during PIT at different intratumor locations ( e.g. , tumor surface vs. deep tumor) in situ and in real time simultaneously. This enabled evaluation of the therapeutic effects in vivo and treatment regimens. The average IR700 fluorescence intensity recovery after PIT to the tumor surface is 91.50%, while it is 100.63% in deep tumors. To verify the results, two-photon microscopy combined with a microprism was also used to record the mAb-IR700 distribution and fluorescence intensity of green fluorescent protein (GFP) at different tumor depths during PIT. After PIT treatment, there was significantly higher IR700 fluorescence recovery in deep tumor than in the tumor surface. This phenomenon can be explained by increased vascular permeability immediately after NIR-PIT. Fluorescence intensity of GFP at the tumor surface decreased significantly more compared to that of deep tumor and in controls (no PIT). [ABSTRACT FROM AUTHOR]

Even with the advances of conventional treatment techniques, the nervous system cancer prognosis is still not favorable to the patient which makes alternative therapies needed to be studied. Photodynamic therapy (PDT) is presented as a promising therapy, which employs a photosensitive (PS) agent, light wavelength suitable for the PS agent, and molecular oxygen, producing reactive oxygen species in order to induce cell death. The aim of this study is to observe the PDT action in gliosarcoma cell using a chlorin (Photodithazine, PDZ). The experiments were done with 9L/lacZ lineage cells, grown in a DMEM medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin solution and put in a culture chamber at 37 °C with an atmosphere of 5% CO2. The PS agent used was the PDZ to an LED light source device (Biopdi/IRRAD-LED 660) in the 660-nm region. The location of the PS agent was analyzed by fluorescence microscopy, and cell viability was analyzed by MTT assay (mitochondrial activity), exclusion by trypan blue (cell viability), and morphological examination through an optical microscope (Leica MD 2500). In the analysis of the experiments with PDZ, there was 100% cell death at different concentrations and clear morphological differences in groups with and without treatment. Furthermore, it was observed that the photodithazine has been focused on all nuclear and cytoplasmic extension; however, it cannot be said for sure whether the location is in the inside core region or on the plasma membrane. In general, the PDZ showed a promising photosensitive agent in PDT for the use of gliosarcoma. [ABSTRACT FROM AUTHOR]

Magnetofluorescent carbon quantum dots (MCQDs) have attracted significant attention in biomedical studies due to their major role in cancer photothermal therapeutics. We synthesized the FeN@CQDs with intrinsic photoluminescent and magnetic properties with a green, hydrothermal method. These magnetofluorescent FeN@CQDs were conjugated with a folic acid and riboflavin (Rf-FA-FeN@CQDs) as the light-triggered theranostics for simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT). In order to reduce Rf-FA-FeN@CQDs biological toxicity, we used a highly efficient cross-linking reaction to incorporate Rf-FA-FeN@CQDs nanostructures into polymer nanospheres. Doxorubicin, an anticancer drug, was further incorporated into the GP-Rf-FA-FeN@CQDs to form GP-Rf-FA-FeN@CQDs-DOX to enable targeted drug delivery. The uptake into cancer cells and the intracellular location of the GP-Rf-FA-FeN@CQDs-DOX were observed by confocal laser scanning microscopy. The results of both in vitro and in vivo experiments reveal that the developed can deliver anti-cancer drugs to target cells, release them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photo synergistic therapeutic effect. [ABSTRACT FROM AUTHOR]

Targeted theranostic nano-system integrating functions of both diagnosis and therapy shows great potential for improving diagnosis and therapeutic efficacy. Herein, multifunctional nanoparticle based on activatable hyaluronic acid (HA) conjugating two near-infrared (NIR) dyes of Cy5.5 and IR825 was successfully designed and fabricated, and simultaneously used as a carrier for encapsulating perfluorooctylbromide (PFOB). In this system, PFOB showed good capability to absorb the X-rays, Cy5.5 on the outer surface acted as a fluorescent dye activatable by hyaluronidases (Hyals) in the tumor, and IR825 in the core as a photothermal agent. The obtained nanoparticles (NPs) of PFOB@IR825-HA-Cy5.5 can be utilized for triple X-ray computed tomography (CT), fluorescence and photoacoustic imaging. When PFOB@IR825-HA-Cy5.5 NPs were intravenously injected into the mice bearing HT-29 tumor, efficient tumor accumulation was clearly observed, as revealed by the triple modal imaging. An in vivo tumor treatment experiment was conducted by combination of PFOB@IR825-HA-Cy5.5 and near-infrared laser irradiation, achieving effective tumor ablation in mice. Therefore, PFOB@IR825-HA-Cy5.5 NPs is a safe, efficient, imageable photothermal nanoprobe, showing great potential for cancer theranostics. [ABSTRACT FROM AUTHOR]

Titanium nitride, an alternative plasmonic material to gold with unique physiochemical properties, has been widely used in microelectronics, biomedical devices and food-contact applications. However, its potential application in the area of biomedicine has not been effectively explored. With the spectral match of their plasmon resonance band and the biological transparency window as well as good biocompatibility, titanium nitride nanoparticles (TiN NPs) are promising photoabsorbing agents for photothermal therapy (PTT) and photoacoustic imaging. Nevertheless, the photothermal performance of TiN NPs has not been investigated until now. Here, we presented the investigation of employing TiN NPs as photoabsorbing agents for in vivo photoacoustic tomography (PAT) imaging-guided photothermal cancer therapy. Our experimental results showed that TiN NPs could strongly absorb the NIR light and provided up to 48% photothermal conversion efficiency. After PEGylation, the resultant nanoparticles demonstrated improved physiological stability and extensive blood retention. Following intravenously administration, they could simultaneously enhance the photoacoustic signals of the tumor region and destroy tumors in the tumor-bearing mouse model by taking advantage of the photothermal effect of the TiN NPs. Our findings highlighted the great potential of plasmonic TiN NPs in detection and treatment of cancer. [ABSTRACT FROM AUTHOR]

5-aminolevulinc acid (5-ALA)-based photodynamic therapy (PDT) and photodiagnosis (PD) present many advantages over treatments with conventional photosensitizers (PS). It offers great tumor specificity, reduced photosensitivity reactions caused by PS accumulation in non-targeted tissues and also inherent PS metabolism into endogenous non-fluorescent heme. However, chemical instability, low bioavailability and poor pharmacokinetic profile limit systemic efficacy of 5-ALA. Here, we present a comprehensive in vitro evaluation of novel phosphatase-sensitive prodrugs of 5-ALA. These prodrugs are designed to be activated by ubiquitously expressed phosphatases with much improved chemical stability and reduced acute toxicity profile. PpIX kinetic measurements and flow cytometry show accumulation of PpIX upon incubation with phosphatase-sensitive prodrugs in PC3 human prostate cell cancer, MCF7 breast adenocarcinoma, U87MG glioblastoma, T24 bladder cancer and A549 lung carcinoma cells. They revealed a different fluorescence kinetics and dose-response curves for the different types of 5-ALA prodrugs. These experiments have allowed us to identify the most promising cancer cell types for phospho- 5-ALA prodrugs. Confocal fluorescence microscopy provided further evidence of fluorescent protoporphyrin IX accumulation and sub-cellular localisation. These findings, together with the low toxicity profile of phosphatase-sensitive prodrugs of 5-ALA and good response to PDT provide solid basis for future translational development in PC3, MCF7 and U87MG cancer types. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is over-expressed in the epithelium of prostate cancer and in the neovasculature of many non-prostate solid tumors. PSMA has been increasingly used as a target for cancer imaging and therapy. Here we describe a low-molecular-weight theranostic photosensitizer, YC-9 , for PSMA-targeted optical imaging and photodynamic therapy (PDT). YC-9 was synthesized by conjugating IRDye700DX N -hydroxysuccinimide (NHS) ester with a PSMA targeting Lys-Glu urea through a lysine-suberate linker in suitable yield. Optical imaging in vivo demonstrated PSMA-specific tumor uptake of YC-9 with rapid clearance from non-target tissues. PSMA-specific cell kill was demonstrated with YC-9 in vitro through PDT in PSMA + PC3-PIP and PSMA − PC3-flu cells. In vivo PDT in mice bearing PSMA + PC3-PIP tumors at 4 h post-injection of YC-9 (A total of four PDT sessions were performed, 48 h apart) resulted in significant tumor growth delay, while tumors in control groups continued to grow. PDT with YC-9 significantly increased the median survival of the PSMA + PC3-PIP tumor mice (56.5 days) compared to control groups [23.5–30.0 days, including untreated, light alone, YC-9 alone (without light) and non-targeted IRDye700DX PDT treatment groups], without noticeable toxicity at the doses used. This study proves in principle that YC-9 is a promising therapeutic agent for targeted PDT of PSMA-expressing tissues, such as prostate tumors, and may also be useful against non-prostate tumors by virtue of neovascular PSMA expression. [ABSTRACT FROM AUTHOR]

A PLGA-based multifunctional biodegradable nanoparticle platform co-harboring hematoporphyrin and indocyanine green has been developed. In vitro studies demonstrate ultrasound and light stimulated generation of cytotoxic reactive oxygen species. In vivo studies show that the ICG component facilitates nIR fluorescence imaging that demonstrates accumulation of IV- administered nanoparticles in tumours. In vivo studies also demonstrate ultrasound- and light-mediated inhibition of tumour growth in animals treated with the platform. Since the platform consists entirely of clinically-approved agents it could find use in sonodynamic- and photodynamic-based therapies for cancer. Statement of Significance We describe a biocompatible and biodegradable nanoparticle-based platform for use in sonodynamic and photodynamic therapeutic approaches for the treatment of cancer. The non-toxic nanoparticles produce cytotoxic reactive oxygen species when exposed to ultrasound and/or light at levels that have no impact on tissues. The system is unique in that it is accumulated by tumours within six hours and has the ability to release its sensitising capability while retaining its imaging capability within a therapeutic time frame. The former could enhance dispersion and sensitising capabilities in less permeable tumour tissues and the latter permits the design of therapeutic approaches that minimize collateral damage to normal tissues. [ABSTRACT FROM AUTHOR]

In this study, an intelligent drug delivery system was developed by capping doxorubicin (DOX)-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with superparamagnetic iron oxide nanoparticles (IONPs). Under near infrared (NIR) light irradiation, the versatile HMCuS NPs could exploit the merits of both photothermal therapy (PTT) and photodynamic therapy (PDT) simultaneously. Herein, the multifunctional IONPs as gatekeeper with the enhanced capping efficiency were supposed to realize “zero premature release” and minimize the adverse side effects during the drug delivery in vivo. More importantly, the hybrid metal nanoplatform (HMCuS/DOX@IONP-PEG) allowed several emerging exceptional characteristics. Our studies have substantiated the hybrid nanoparticles possessed an enhanced PTT effect due to coupled plasmonic resonances with an elevated heat-generating capacity. Notably, an effective removal of IONP-caps occurred after NIR-induced photo-hyperthermia via weakening of the coordination interactions between HMCuS-NH 2 and IONPs, which suggested the feasibility of sophisticated controlled on-demand drug release upon exposing to NIR stimulus with spatial/temporal resolution. Benefiting from the favorable magnetic tumor targeting efficacy, the in vitro and in vivo experiments indicated a remarkable anti-tumor therapeutic efficacy under NIR irradiation, resulting from the synergistic combination of chemo-phototherapy. In addition, T 2 -weighted magnetic resonance imaging (MRI) contrast performance of IONPs provided the identification of cancerous lesions. Based on these findings, the well-designed drug delivery system via integration of programmed functions will provide knowledge for advancing multimodality theranostic strategy. Statement of Significance As we all know, a series of shortcomings of conventional chemotherapy such as limited stability, rapid clearing and non-specific tumor targeting ability remain a significant challenge to achieve successful clinical therapeutic efficiency in cancer treatments. Fortunately, developing drug delivery system under the assistance of multifunctional nanocarries might be a great idea. For the first time, we proposed an intelligent drug delivery system by capping DOX-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with multifunctional IONPs to integrate programmed functions including enhanced PTT effect, sophisticated controlled drug release, magnetic targeting property and MR imaging. The results showed HMCuS/DOX@IONP-PEG could significantly enhance anti-tumor therapeutic efficacy due to the synergistic combination of chemo-phototherapy. By this delicate design, we believe such smart and extreme versatile all-in-one drug delivery platform could arouse broad interests in the fields of biomaterials, nanotechnology, and drug delivery system. [ABSTRACT FROM AUTHOR]