Search

Photothermal therapy (PTT) is a promising alternative treatment for bacterial infection. In this study, a photothermal nanoparticle was prepared by encapsulating IR780 into N -octyl- D -gluconamide (GA). The photothermal nanoparticle (IR780-GA NP) was evenly suspended in water with an average particle size of 42.2 nm. After exposure to near-infrared light, the temperature of the IR780-GA NP suspension was increased by around 15 °C within 5 min. This leads to an obvious microbial inactivation effect when it is adsorbed to methicillin-resistant Staphylococcus aureus (MRSA, 2 orders of magnitude reduction of CFU concentration) and Escherichia coli (1.5 orders of magnitude reduction of CFU concentration). Interestingly, Salmonella typhimurium survived after the same treatment. Different strains also showed variations. The hemolysis test showed that IR780-GA NPs had good blood compatibility. In vivo experiments collaborated with the in vitro findings. The IR780-GA NP-triggered photothermal effects killed 63–100% of bacteria in the wound site of mice depending on the IR780-GA NP concentration. Overall, this study provided the fundamental basis of IR780-GA NPs in four aspects: fabrication, photothermal characterization, selective adsorption, and microbial inactivation (in vitro and in vivo). The findings of this study provide a practical approach for the development of mild photothermal therapy which targets specific bacterial strains and treats MRSA infection effectively. [Display omitted] • IR780-gluconamide (GA) NPs showed good photothermal properties. • The IR780-GA NPs treatment selectively inactivated S. aureus and E. coli. • The IR780-GA NPs treatment killed 63–100% of bacteria in the wound site of mice. • The IR780-GA NPs treatment was more effective than vancomycin in the skin infection mouse model. [ABSTRACT FROM AUTHOR]

[Display omitted] • NIR-sensitive, ROS generating, targeting capable nanoplatforms are attractive in cancer therapy. • IR780-modified Ti 3 C 2 nanosheets were prepared as NIR-triggered nanoplatforms to treat laryngeal cancer through the mitochondrial-dependent apoptosis pathway. • The obtained multifunctional materials hold promising potential for laryngeal cancer treatment. Laryngeal cancer is the most common malignant tumor for which there is still a lack of effective treatment. Traditional radiotherapy, chemotherapy, and surgery all have significant side effects. Therefore, multifunctional collaborative therapeutic nanoplatforms are attractive to patients with laryngeal cancer. In this study, a near-infrared responsive IR780-modified MXene (Ti 3 C 2) nanosheet was proposed as a strategy for targeted therapy to achieve the synergistic functions of photothermal (PTT) therapy, photodynamic (PDT) therapy and mitochondrial pathway apoptosis. Electron spin resonance results showed that Ti 3 C 2 @IR780 could produce singlet linear oxygen for PDT. Molecular biology studies showed that Ti 3 C 2 @IR780 had the outstanding ability to generate ROS to disrupt mitochondrial function, resulting in apoptosis of cancer cells up to 60.51%. In vivo experiments showed that Ti 3 C 2 @IR780 could effectively aggregate at tumor sites. The temperature of the tumor region could reach 63.7 °C in the presence of near-infrared light. Tumor growth was inhibited by 92% during the treatment, and there was no recurrence. Results of the sections showed an 88.1% reduction in microtumor vascularity with Ti 3 C 2 @IR780 treatment for 21 days compared to the control group. These findings suggest that this multifunctional nanoplatform with synergistic NIR-sensitive properties can effectively inhibit tumor growth, providing an ideal strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Combined photo-induced cancer therapy (photothermal therapy (PTT) and photodynamic therapy (PDT)) is a promising anti-cancer strategy for its non-invasiveness property. However, severe hypoxia in tumor microenvironment (TME) would weaken the PDT effect and limit the clinical efficiency of PTT/PDT treatment. To solve this problem, denatured BSA-hemin-IR780 (dBHI) was designed and synthesized for anti-cancer treatment in this work. Denatured bovine serum albumin (dBSA) was used as the binding matrix to bind hemin and IR780 via covalent reaction and hydrophobic self-assembly, respectively. The obtained dBHI nanoparticles possess both PTT and PDT effect due to the presence of IR780 in the composites. Moreover, because of the existence of hemin, dBHI also exhibited photo-enhanced Fenton-like catalytic performance, which could decompose H 2 O 2 to form oxygen for improving the PDT effect and generate hydroxyl radical (·OH) for chemodynamic therapy (CDT). Therefore, by using dBHI, synergistic effect of PTT/PDT/CDT combined treatment has been achieved for cancer therapy. Denatured BSA-hemin-IR780 (dBHI) was fabricated for combined PDT/PTT/CDT treatment of cancer. The PDT effect was significantly enhanced by the in situ generated oxygen in the CDT process. The CDT effect could also be promoted by the photo-induced therapy due to the accelerating H 2 O 2 decomposition by light and heating. With synergistic effect of combined PTT, PDT and CDT, dBHI can effectively inhibit growth of cancer cells [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scars (HS) represent one of the most common clinical challenges due to unsatisfactory therapeutic results. HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior. Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation. This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation., Methods: Here, augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts (HFs) and HS tissues, and the suppression of glycolysis also attenuated fibroblast activation. We also introduced IR780, a heptamethine cyanine dye, to regulate glycolysis for the control of HS formation., Results: In vitro , cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs. In vivo, the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation. Furthermore, IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies, and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts., Conclusions: This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts., (© The Author(s) 2022. Published by Oxford University Press.)

IR780 is a near-infrared fluorescent dye, which can be applied as a photosensitizer in photodynamic (PDT) and photothermal (PTT) therapies and as a biodistribution tracer in imaging techniques. We investigated the growth and migration inhibition and mechanism of death of breast tumor cells, MCF-7 and MDA-MB-231, exposed to polymeric nanocapsules (NC) comprising IR780 covalently linked to the biodegradable polymer PLA (IR-PLA) and IR780 physically encapsulated (IR780-NC) in vitro. Both types of NC had mean diameters around 120 nm and zeta potentials around −40 mV. IR-PLA-NC was less cytotoxic than IR780 NC to a non-tumorigenic mammary epithelial cell line, MCF-10A, which is an important aspect of selectivity. Free-IR780 was more cytotoxic than IR-PLA-NC for MCF-7 and MDA-MB-231 cells after illumination with a 808 nm laser. IR-PLA NC was effective to inhibit colony formation (50%) and migration (30–40%) for both cancer cell lines. MDA-MB-231 cells were less sensitive to all IR780 formulations compared to MCF-7 cells. Cell uptake was higher with IR-PLA-NC than with IR780-NC and free-IR780 in both cancer cell lines (p < 0.05). NC uptake was higher in MCF-7 than in MDA-MB-231 cells. IR-PLA-NC induced a higher percentage of apoptosis upon illumination in MDA-MB-231 than in MCF-7 cells. The necrosis mechanism of death predominated in treatments with free-IR780 and with encapsulated IR780 NC, suggestive of damages at the plasma membrane. IR780 conjugated with PLA increased the apoptotic pathway and demonstrated potential as a multifunctional theranostic agent for breast cancer treatment with increased cellular uptake, photodynamic activity and more reliable tracking in cell-image studies. [Display omitted] • IR780 conjugated to PLA (IR-PLA) maintains its photodynamic activity in cancer cells. • IR-PLA has higher cell-uptake than IR780 physically encapsulated in nanocapsules. • IR-PLA increases the contribution of apoptosis in cancer cell death. [ABSTRACT FROM AUTHOR]

Virus-like particles (VLPs) holding internal cavity with diameter from tens up to one hundred nanometers are attractive platform for drug delivery. Nevertheless, the packing of drugs in the nanocage mainly relies on complicated disassembly-reassembly process. In this study, hepatitis B core protein (HBc) VLPs which can withstand temperature up to 90 °C was employed as carrier to load a lipophilic near infrared dye IR780. It was found that an attaching-dis-atching-diffusing process was involved for the entering of IR780 in the cavity of HBc. The first two steps were associated with the electrostatic interactions between oppositely charged HBc and IR780, which was critically manipulated by ionic strength and HBc/IR780 mass ratio at which they were mixed; while the diffusion of IR780 across the shell of HBc showed a temperature-dependent manner that can be triggered by thermal induced pore-opening of the HBc capsid. At optimized condition, about 1055 IR780 molecules were encapsulated in each HBc by simply mixing them for 10 min at 60 °C. Compared with free IR780, the HBc-IR780 particles showed significantly improved aqueous and photostability, as well as enhanced photothermal and photodynamic performance for cancer therapy. This study provides a novel drug loading strategy and nanomemedicine for cancer phototherapies. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) bacterial strains have emerged and weakened the therapeutic effects of antibacterial drugs. Sonodynamic therapy (SDT) takes advantage of noninvasiveness and deep tissue-penetrating features and has been rejuvenated to combat MDR bacteria and their biofilm-associated infections. To improve the efficacy of antibacterial SDT, we first developed IR780-based PLGA nanoparticles as sonosensitizers for high-frequency ultrasound (US)-monitored antibacterial SDT of MRSA myositis by therapeutic low-frequency US. In this study, the developed shell-core-structured IR780@PLGA nanoparticles were designed with a polymer shell PLGA with the sonosensitizer IR780 loaded on. High-frequency diagnostic US was introduced to monitor the sonotherapeutic progression of bacterial myositis by therapeutic low-frequency US. Importantly, the in vitro and in vivo results confirmed that IR780@PLGA nanoparticles combined with US irradiation possess high efficiency for antibacterial therapy. This approach provides a simple and efficient strategy to monitor and combat MDR bacterial infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wang, Tang, Chen, Xu, Liao and Niu.)

Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs. Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo . Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo . Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Transdermal drug delivery for local or systemic therapy provides a potential anticancer modality with a high patient compliance. However, the drug delivery efficiency across the skin is highly challenging due to the physiological barriers, which limit the desired therapeutic effects. In this study, we prepared liposome-in-hydrogels containing a tumor targeting photosensitizer IR780 (IR780/lipo/gels) for tumor photothermal therapy (PTT). The formulation effectively delivered IR780 to subcutaneous tumor and deep metastatic sites, while the hydrogels were applied on the skin overlying the tumor or on an area of distant normal skin. The photothermal antitumor activity of topically administered IR780/lipo/gels was evaluated following laser irradiation. We observed significant inhibition of the rate of the tumor growth without any toxicity associated with the topical administration of hydrogels. Collectively, the topical administration of IR780/lipo/gels represents a new noninvasive and safe strategy for targeted tumor PTT.

[Display omitted] • A novel injectable in situ forming chitosan-based hydrogel was prepared for chemo-PTT. • The NIR-responsive hydrogels could produce a temperature increase of about 9 °C. • The NIR-light exposure increased the release of DOX from the hydrogel by 1.7-times. • The chemo-PTT mediated by the hydrogel reduced the viability of cancer cells to 9%. Chemo-photothermal therapy (chemo-PTT) mediated by nanomaterials holds a great potential for cancer treatment. However, the tumor uptake of the systemically administered nanomaterials was recently found to be below 1%. To address this limitation, the development of injectable tridimensional polymeric matrices capable of delivering nanomaterials directly into the tumor site appears to be a promising approach. In this work, an injectable in situ forming ionotropically crosslinked chitosan-based hydrogel co-incorporating IR780 loaded nanoparticles (IR/BPN) and Doxorubicin (DOX) loaded nanoparticles (DOX/TPN) was developed for application in breast cancer chemo-PTT. The produced hydrogels (IR/BPN@Gel and IR/BPN+DOX/TPN@Gel) displayed suitable physicochemical properties and produced a temperature increase of about 9.1 °C upon exposure to Near Infrared (NIR) light. As importantly, the NIR-light exposure also increased the release of DOX from the hydrogel by 1.7-times. In the in vitro studies, the combination of IR/BPN@Gel with NIR light (photothermal therapy) led to a reduction in the viability of breast cancer cells to 35%. On the other hand, the non-irradiated IR/BPN+DOX/TPN@Gel (chemotherapy) only diminished cancer cells' viability to 85%. In contrast, the combined action of IR/BPN+DOX/TPN@Gel and NIR light reduced cancer cells' viability to about 9%, demonstrating its potential for breast cancer chemo-PTT. [ABSTRACT FROM AUTHOR]

Phototherapy exerts its anticancer effects by converting laser radiation energy into hyperthermia or reactive singlet oxygen (1O 2). In this study, we developed chitosan nanoparticles (CS NPs) encapsulating both photothermal (IR780) and photodynamic (5-Aminolevulinic acid (5-ALA)) reagents for photothermally enhanced photodynamic therapy by noninvasive oral administration. The 5-ALA&IR780@CS NPs were stable in acidic conditions similar to the gastric environment, which greatly improved drug oral absorption and local accumulation in subcutaneous mouse colon tumors (CT-26 cells) following oral gavage. Mechanistic studies revealed that the co-delivery system can lead to photothermally enhanced photodynamic effects against cancer cells by increasing oxidative stress, including the elevation of ROS, superoxide and 1O 2 production. Additionally, significant therapeutic efficacy for cancer treatment were observed in vivo after oral administration of 5-ALA&IR780@CS NPs, without causing any overt adverse effects. Our work highlights the great potential of photothermally enhanced photodynamic therapy by CS NPs for colon cancer management via oral route. [ABSTRACT FROM AUTHOR]

• Nanomedicne aiming to tackle the potential risk of ICB, e.g. irAEs was developed. • Molecular engineering strategy was used to precisely control the loading content of anti-PD-L1 peptide (APP). • The synthesized IR780-M-APP molecules obtained a precise loading content of 48.4 wt % APP and 20.2 wt % IR780 respectively. • IR780-M-APP NPs potently enhanced the tumor penetration of IR780 via an enzyme-responsive size change. • IR780-M-APP NPs integrating photodynamic immunotherapy with PD-L1 blocking successfully amplified the antitumor efficacy. Immune checkpoint blockade (ICB) strategy based on suppressing programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has been proved to be promising and effective in cancer immunotherapy. However, its potential risk of immune-related adverse events (irAEs) places stringent requirements on the precise loading of anti-PD-L1 agent in nanomedicine. Precise control of the loading content of anti-PD-L1 antibody is a difficult task since physical encapsulation has inevitable drawbacks like batch-to-bath variation and chemical modification is limited by the low stability of the antibody. Herein, we proposed a molecular engineering strategy to develop the nanomedicine with precise control of anti-PD-L1 agent content by using anti-PD-L1 peptide (APP) as the substitute to anti-PD-L1 antibody. The APP was chemically bonded with a photosensitizer IR780 to obtain IR780-M-APP, a molecule able to self-assemble into nanoparticles (NPs) with a precise APP loading (48.4 wt%) determined by the molecular structure. Specifically, the IR780 moiety in IR780-M-APP NPs endows the nanoparticles with photodynamic therapeutic effect as well as the ability to trigger immunogenic cell death (ICD), while the APP moiety can block the PD-1/PD-L1 pathway for promoting immunotherapy. The proposed photodynamic-immunotherapy nanoplatform not only killed primary tumors directly but also eradicated the metastatic and invasive tumors effectively. The present molecular engineering strategy combined with anti-PD-L1 peptide might provide more opportunities for the design of advanced nanoplatforms for cancer therapy. [ABSTRACT FROM AUTHOR]

• Novel IR780 loaded SBMA-functionalized BSA NPs (IR/SBMA-BSA NPs) were produced. • SBMA-functionalization yielded IR/SBMA-BSA NPs displaying a neutral surface charge. • IR/SBMA-BSA NPs displayed an improved stability in biological relevant media. • IR/SBMA-BSA NPs achieved a 1.9-fold higher uptake by MCF-7 cells. • IR/SBMA-BSA NPs interaction with NIR light enhanced the therapeutic outcome. New insights about nanomaterials' biodistribution revealed their ability to achieve tumor accumulation by taking advantage from the dynamic vents occurring in tumor's vasculature. This paradigm-shift emphasizes the importance of extending nanomaterials' blood circulation time to enhance their tumor uptake. The classic strategy to improve nanomaterials' stability during circulation relies on their functionalization with poly(ethylene glycol). However, recent reports have been showing that PEGylated nanomaterials can suffer from the accelerated blood clearance phenomenon, emphasizing the importance of developing novel coatings for functionalizing the nanomaterials. To address this limitation, the modification of natural carriers' surface to enhance their stability appears to be a promising strategy. Herein, sulfobetaine methacrylate (SBMA)-functionalized bovine serum albumin (BSA) was synthesized for the first time to investigate the capacity of this modification to improve the resulting nanoparticles' physicochemical properties, colloidal stability and in vitro performance. This novel polymer was then employed in the formulation of nanoparticles loaded with IR780 for application in breast cancer phototherapy (IR/SBMA-BSA NPs). When compared to their non-functionalized equivalents, the IR/SBMA-BSA NPs presented a neutral surface charge and a higher stability in biologically relevant media. Due to these features, the IR/SBMA-BSA NPs could achieve a 1.9-fold greater uptake by breast cancer cells than IR/BSA NPs. Furthermore, the IR/SBMA-BSA NPs were cytocompatible towards normal cells and reduced breast cancer cells' viability up to 42%. The phototherapy mediated by IR/SBMA-BSA NPs could further decrease cancer cells' viability to about 12%. Overall, the IR/SBMA-BSA NPs have enhanced features that propel their application in breast cancer phototherapy. [ABSTRACT FROM AUTHOR]

• A new therapy nanoplatform of biotin-tailored IR780 and quercetin was designed. • Excellent active tumor-targeted and pH-responsive capability were demonstrated. • The poor water solubility of both IR780 and quercetin were efficiently solved. • A low side-effect formulation was demonstrated. • Heat-shock protein-inhibited strategy improved chemo-phototherapy capability. The side effects of anticancer drugs and tumor tolerance from heat shock protein expression are still a bottleneck for the current chemo-phototherapy. Although quercetin (Qu) is a naturally low-side effect anticancer drug and heat shock protein inhibitor for tailoring phototherapy, it is largely restricted by poor water solubility. Moreover, the near-infrared dye IR780-iodide (IR780), as a promising phototherapy agent, is also restricted from clinical applications due to its poor water solubility. Herein, we rationally designed a robust low side-effect and heat-shock protein-inhibited chemo-phototherapy nanoplatform via co-assembly of biotin-tailored IR780 (B780) and quercetin, defined as B780/Qu nanoparticles (B780/Qu NPs), which efficiently solved the poor water solubility of both IR780 and Qu. Moreover, the B780 endowed B780/Qu NPs with superior active tumor-targeted property and pH-responsive drug delivery. Thanks to the combination of chemo-phototherapy, the B780/Qu NPs with near infrared (NIR) laser irradiation exhibited excellent anti-tumor efficacy. Therefore, our B780/Qu NPs are very promising as an efficient low side-effect and heat-shock protein-inhibited chemo-phototherapy nanoplatform against tumors. [ABSTRACT FROM AUTHOR]

• TAT peptide-conjugated IR780 (TAT-IR780) was synthesized. • TAT-IR780 and doxorubicin (DOX) self-assembled to form TID nanoparticles. • TID nanoparticles exhibited excellent cellular uptake and nucleus-targeting ability. • TID nanoparticles showed synergistic antitumor effects of PTT/PDT and chemotherapy. Breast cancer is the most common malignant tumor in women. Phototherapy, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), shows many advantages such as high spatial selectivity, noninvasive nature, and negligible drug resistance for breast cancer treatment. Additionally, recent investigations have shown that nucleus-targeted PTT can kill cancer cells more directly and more efficiently by "burning" cell nuclei closely. In this study, we developed a nucleus-targeting nanoparticle system for combining PTT/PDT and chemotherapy to treat breast cancer. IR780, a near-infrared (NIR) fluorescence dye that has potent anticancer efficacy of PTT and PDT, was firstly conjugated with TAT peptide through substitution reaction between chlorine atom and sulfhydryl group, thus obtained a conjugate TAT-IR780 with notably enhanced water solubility and optical stability. Next, chemotherapeutic drug doxorubicin (DOX) and TAT-IR780 self-assembled in aqueous medium to form TID nanoparticles with a small size of approximately 100 nm. Both in vitro and in vivo , TID nanoparticles showed greatly enhanced PTT/PDT efficiencies as compared with free IR780. Through the mediation of TAT peptide, TID nanoparticles significantly improved the cellular internalization of IR780 in breast cancer cells and delivered it mostly to the perinuclear region. Upon laser irradiation at 785 nm, TID nanoparticles rapidly destroyed the genetic substances and potently induced the apoptosis of breast cancer cells. In the mice bearing breast cancer, intratumoral injection of TID nanoparticles with local laser irradiation realized fluorescence and photothermal imaging-guided combination treatment of nucleus-targeted PTT/PDT and chemotherapy, and achieved significant synergistic effects on breast tumor ablation and recurrence. In summary, this study provides a nucleus-targeting nanoplatform for dual imaging-guided photo-chemotherapy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Biofilms have been related to the persistence of infections on medical implants, and these cannot be eradicated because of the resistance of biofilm structures. Therefore, a biocompatible phototherapeutic system is developed composed of MoS2, IR780 photosensitizer, and arginine–glycine–aspartic acid–cysteine (RGDC) to safely eradicate biofilms on titanium implants within 20 min. The magnetron‐sputtered MoS2 film possesses excellent photothermal properties, and IR780 can produce reactive oxygen species (ROS) with the irradiation of near‐infrared (NIR, λ = 700–1100 nm) light. Consequently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT), assisted by glutathione oxidation accelerated by NIR light, can provide synergistic and rapid killing of bacteria, i.e., 98.99 ± 0.42% eradication ratio against a Staphylococcus aureus biofilm in vivo within 20 min, which is much greater than that of PTT or PDT alone. With the assistance of ROS, the permeability of damaged bacterial membranes increases, and the damaged bacterial membranes become more sensitive to heat, thus accelerating the leakage of proteins from the bacteria. In addition, RGDC can provide excellent biosafety and osteoconductivity, which is confirmed by in vivo animal experiments. [ABSTRACT FROM AUTHOR]

Activatable photodynamic therapy (A-PDT) has attracted great attention in precision medicine, which can be activated by endogenous or exogenous stimuli to selectively produce reactive oxygen species (ROS) at the disease site. Thermal responsive polymers with a lower critical solution temperature (LCST) have normally been utilized for constructing A-PDT system. Herein, we fabricated a photothermal activatable photosensitizer (A-PS) by the combination of thermal responsive porphyrin-containing P(AAm- co -AN- co -TPP)- b -POEGMA amphiphilic block copolymer with an upper critical solution temperature (UCST) of 42 °C and a cyanine dye of IR780. The photoactivity of porphyrin units could be severely inhibited by IR780 due to the fluorescence resonance energy transfer (FRET) from TPP to IR780 during blood circulation process ("OFF" state). After an uptake by A549 cells and then irradiated with 808 nm laser, A-PS nanoparticles were subsequently dissociated owing to the increased local temperature above the UCST of the polymer chains by excellent photothermal conversion of IR780, resulting in the enhanced photoactivity of TPP ("ON" state) and the remarkable antitumor effect. Therefore, the UCST-based A-PS extended the biological application of thermal responsive polymers, which may provide a new insight into the design of smart cancer therapeutic systems.

The near-infrared fluorescent (NIRF) dye, IR780, is recognized as a promising theranostic agent and has been widely investigated for imaging, chemotherapeutic, and phototherapeutic applications. However, its poor photostability and nonselective toxicities toward both cancer and normal cells limit its biological applications. Herein, we introduce the use of GUMBOS (a group of uniform materials based on organic salts) developed through counter-anion exchange with IR780 and subsequent nanomaterials (nanoGUMBOS) formed by complexation with cyclodextrin (CD) for enhanced chemo/photothermal therapy. Such CD-based nanoGUMBOS display improved aqueous stability, photostability, and photothermal effects relative to traditional IR780. The examination of in vitro cytotoxicity reveals that CD-based nanoGUMBOS are selectively toxic toward cancer cells and exhibit synergistically enhanced cytotoxicity toward cancer cells upon NIR laser irradiation. Additionally, in vivo NIRF imaging demonstrated selective accumulation of these nanoGUMBOS within the tumor site, indicating tumor-targeting properties. Further in vivo therapeutic study of these CD-based nanoGUMBOS suggests excellent chemo/photothermal antitumor effects. Using these studies, we herein demonstrate a promising strategy, via conversion of IR780 into nanoGUMBOS, that can be used for improved theranostic cancer treatment.

Rationale: Recently, there is one-fifth of human deaths caused by cancer, leading to cancer treatment remains a hard nut to crack in the medical field. Therefore, as an emerging diagnostic technology, mesoporous nanomaterials-based drug delivery systems integrated diagnosis and therapy have aroused tremendous interest owing to visually targeting effect and superior therapy efficacy compared with traditional cancer treatment. Methods: In this work, we have successfully synthesized mesoporous carbon-gold hybrid nanozyme nanoprobes, whereby mesoporous carbon nanospheres were doped with small gold nanoparticles (OMCAPs) and further stabilized with a complex of reduced serum albumin and folic acid (rBSA-FA). After loading IR780 iodide, the OMCAPs@ rBSA-FA@IR780 nanoprobes were finally accomplished for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy. Results: Herein, acid oxidized MCAPs possessed large surface area and numerous -COOH groups, which could be used to surface chemically modify numerous targeting molecules and load abundant NIR dye IR780, as well as be acted as photothermal reagents to enhance photothermal therapy effect. In addition, the small Au NPs embedded in OMCAPs were utilized as nanozyme to catalyze H 2 O 2 located in tumor cells to generate ·OH for intracellular oxidative damage of tumor. Besides, as a commonly used near-infrared (NIR) fluorescence dye, the loaded IR780 iodide could not only apply for real-time imaging, but also effectively enhance photo-thermal therapy (PTT) upon the 808 nm laser irradiation. Moreover, FA molecules could enhance the targeted efficiency of the nanoprobes to the gastric tumor site. According to the systematical study in vitro and in vivo , our fabricated nanoprobes based on carbon-gold hybrid (OMCAPs@ rBSA-FA@IR780) revealed excellent tumor targeting efficacy, long tumor retention and favorably therapeutic effect for tumor. Conclusion: All the results demonstrated that here synthesized probes exhibited excellently diagnostic and therapeutic performance, indicating our technology may potentially offer an outstanding strategy for tumor-targeting theranostics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Due to the good transparency of the human tissue in the biological spectral window, near-infrared (NIR)-dye loaded nanosystems enable more effective light-activated therapy and better contrast imaging with major impact on nanomedicine. Herein, we prepare Pluronic coated gold nanoparticles incorporating the hydrophobic NIR dye, IR780 iodide (GNP-Plu-IR780) to provide water-solubility and stability and demonstrate the proficiency of combining photodynamic and photothermal therapeutic activity with surface-enhanced resonance Raman scattering (SERRS) imaging facility. The potential of GNP-Plu-IR780 to operate as NIR-activatable agents was first assessed in aqueous solution by singlet oxygen generation measurements and monitoring the temperature increase of the nanoparticles. Subsequent in vitro uptake studies by dark field and differential interference contrast (DIC) microscopy reveal massive internalization of GNP-Plu-IR780 by murine colon carcinoma cells (C-26). Moreover, by exploiting the SERRS effect under 785 nm laser excitation we were able to perform intracellular tracking of GNP-Plu-IR780. Finally, NIR irradiation experiments conducted in vitro against C-26 cells show efficient phototherapeutic activity induced by GNP-Plu-IR780 with no dark cytotoxicity. Moreover, when compared to the administration of free drug or non-loaded GNP-Plu, the higher phototherapeutic activity of GNP-Plu-IR780 indicates the occurrence of cooperative synergistic effects by simultaneous photodynamic and photothermal activity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A multifunctional albumin/superparamagnetic iron oxide nanoparticle (SPIO) nanocomplex system to deliver IR780, a photothermal agent, for cancer theranostic applications was proposed in this study. Single emulsion method was utilized to fabricate the human albumin/IR780/SPIO (HISP) nanocomplexes with a hydrophobic core (SPIO and IR780) and a hydrophilic shell (human serum albumin (HSA) and poly (ethylene glycol) (PEG)). Effects of PEGylation on the size and surface potential of nanocomplexes were analyzed. Nanospheres containing uniformly dispersed SPIO was observed using Transmission Electron Microscopy (TEM) imaging. As a potential magnetic resonance (MR) imaging agent, the HISP displayed dose-dependent T2-weighted imaging contrast (R2 = 81.6 mM -1 s -1 ). Good colloidal stability was verified from the nanocomplexes under difference circumstances. The nanocomplexes were taken up by cancer cells efficiently and led to significant photothermal-mediated cancer cell death upon short-term near infrared (NIR) irradiation in vitro . Via intravenous injection, PEG-HISP can efficiently deliver IR780 to tumor sites and showed strong photothermal effect compared to free drug on the mice model. Significant tumor suppression by the photothermal treatments using PEG-HISP was demonstrated from the mice CT26 xenograft model. Good safety profile of the PEG-HISP was confirmed from histological examination and liver functional analysis. Taken together, the results suggest that PEG-HISP is a safe and robust nano-theranostic platform for advanced anti-cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Cancer research regarding near-infrared (NIR) agents for chemothermal therapy (CTT) has shown that agents with specific functions are able to inhibit tumor growth. The aim of current study was to optimize CTT efficacy for treatment of colorectal cancer (CRC) by exploring strategies which can localize high temperature within tumors and maximize chemotherapeutic drug uptake. We designed a new and simple multifunctional NIR nanoagent composed of the NIR cyanine dye, polyethylene glycol, and a cyclic arginine-glycine-aspartic acid peptide and loaded with the anti-CRC chemotherapeutic agent, 7-ethyl-10-hydroxy-camptothecin (SN38). Each component of this nanoagent exhibited its specific functions that help boost CTT efficacy. The results showed that this nanoagent greatly strengthens the theranostic effect of SN38 and CTT against CRC due to its NIR imaging ability, photothermal, enhanced permeability and retention (EPR) effect, reticuloendothelial system avoidance, and angiogenic blood vessel-targeting properties. This NIR nanoagent will help facilitate development of new strategies for treating CRC.

Photothermal therapy exerts its anticancer effect by converting laser radiation energy into hyperthermia using a suitable photosensitizer. This study reports development of nanostructured lipid carriers (NLCs) suitable for noninvasive oral delivery of a near-infrared photosensitizer dye IR780. The carrier encapsulating the dye (IR780@NLCs) was stable in simulated gastric and intestinal conditions and showed greatly enhanced oral absorption of IR780 when compared with the free dye. As a result of increased oral bioavailability, enhanced accumulation of the dye in subcutaneous mouse colon tumors (CT-26 cells) was observed following oral gavage of IR780@NLCs. Photothermal antitumor activity of orally administered IR780@NLCs was evaluated following local laser irradiation of the CT-26 tumors. We observed significant effect of the photothermal IR780@NLCs treatment on the rate of the tumor growth and no toxicity associated with the oral administration of IR780@NLCs. Overall, orally administered IR780@NLCs represents a safe and noninvasive method to achieve systemic tumor delivery of a photosensitizing dye for applications in photothermal anticancer therapies.

PEG-IR780-C13 micelles have been demonstrated to be a novel photothermal agent with tumor-targeting property. This study was designed to explore the feasibility of applying PEG-IR780-C13 micelles and near-infrared (NIR) irradiation for thermal ablation of renal tumor by using an in situ tumor model. In addition, the potential thermal injury to normal renal tissue was evaluated. PEG-IR780-C13 micelles were intended to accumulate in renal tumor after systemic delivery. In vitro results revealed that PEG-IR780-C13 micelles were uptaken by RENCA cells mainly through caveola-mediated endocytosis and mainly distributed in late endosomes and lysosomes. Upon NIR irradiation, PEG-IR780-C13 micelles generated heat effectively both in vitro and in vivo, exhibiting a promising photothermal therapeutic property. The photothermal effect of PEG-IR780-C13 micelles could effectively destroy RENCA cells in vitro and adequately inhibit growth of in situ renal tumor in vivo. Meanwhile, PEG-IR780-C13 micelles mediated photothermal therapy (PTT) resulting in only limited injury to normal renal tissue surrounding tumor sites. Our data indicated that PEG-IR780-C13 micelles mediating PTT could generate tumor-specific heat for destruction of renal tumor in a minimally invasive way, providing a novel strategy for thermal ablation of renal tumor.

The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranostic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.