Bioresponsive Nanoarchitectonics-Integrated Microneedles for Amplified Chemo-Photodynamic Therapy against Acne Vulgaris.

The excessive colonization of Propionibacterium acnes (P. acnes) is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration. Herein, MNs loaded with intelligent pH-sensitive nanoplatforms were constructed for amplified chemo-photodynamic therapy against acne vulgaris, jointly exerting antimicrobial and anti-inflammatory effects. The photosensitizer indocyanine green (ICG) was loaded into the zeolitic imidazolate framework-8 (ZIF-8) to improve its photostability, which would be triggered by 808 nm laser irradiation to generate cytotoxic reactive oxygen species (ROS) to result in oxidative damage and disturbed metabolic activities of P. acnes. In addition to the efficient drug delivery, the ZIF-8 carrier could selectively degrade in response to the acidic microenvironment of acne lesions, and the released Zn2+ also exhibited a potent antimicrobial activity. The fabricated ZIF-8-ICG@MNs presented an outstanding synergistic anti-acne efficiency both in vitro and in vivo. This bioresponsive microneedle patch is expected to be readily adapted as a generalized, modular strategy for noninvasive therapeutics delivery against superficial skin diseases.

Multifunctional Size-Expandable Nanomedicines Enhance Tumor Accumulation and Penetration for Synergistic Chemo-Photothermal Therapy.

Size expansion can effectively improve tumor accumulation of nanocarriers where precise control is required. A dual-responsive nanocarrier stimulated by both endogenous pH and exogenous heat stimuli can change its size. Herein, a nanoparticle composed of poly(N,N-diethyl acrylamide) (PDEAA) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) is developed. The antitumor drug celastrol (CLT) and the photosensitizer indocyanine green (ICG) are then loaded in it to form CIPP. ICG generates heat under near-infrared (NIR) stimulation to kill tumor cells and enhance CIPP penetration. Meanwhile, CIPP expands in response to hyperthermia and acid tumor microenvironments, preventing itself from returning to the blood flow, thus accumulating in tumor sites. Ultimately, the acidic lysosomal environment in tumor cells disintegrates CIPP to release CLT, directly inducing immunogenic cell death and sensitizing tumor cells for hyperthermia by disrupting the interaction of heat shock protein 90 and P50cdc37. Most of the tumors in B16F10-bearing mice are eradicated after single laser irradiation. The dual-responsive CIPP with multiple functions and simple design displays a synergistic antitumor effect. This study provides a basis for developing size-expandable stimulus-responsive drug delivery systems against tumors.

Glucose-Targeted Hydroxyapatite/Indocyanine Green Hybrid Nanoparticles for Collaborative Tumor Therapy.

Nanoscale hydroxyapatite (nHA) is considered as a promising drug carrier or therapeutic agent against malignant tumors. But the strong agglomeration tendency and lack of active groups seriously hamper their usage in vivo. To address these issues, we fabricated an organic-inorganic hybrid nanosystem composed of poly(acrylic acid) (PAA), nHA, and indocyanine green (ICG), and further modified with glucose to give a targeting nanosystem (GA@HAP/ICG-NPs). These hybrid nanoparticles (∼90 nm) showed excellent storage and physiological stability assisted by PAA and had a sustained drug release in an acidic tumor environment. In vitro cell experiments confirmed that glucose-attached particles significantly promoted cellular uptake and increased intracellular ICG and Ca2+ concentrations by glucose transporter 1 (GLUT1)-mediated endocytosis. Subsequently, the excessive Ca2+ induced cell or organelle damage and ICG triggered photothermal and photodynamic effects (PTT/PDT) under laser irradiation, resulting in enhanced cell toxicity and apoptosis. In vivo tests revealed that the hybrid nanosystem possessed good hemocompatibility and biosafety, facilitating in vivo circulation and usage. NIR imaging further showed that tumor tissues had more drug accumulation, resulting in the highest tumor growth inhibition (87.89%). Overall, the glucose-targeted hybrid nanosystem was an effective platform for collaborative therapy and expected to be further used in clinical trials.

Camouflaged Gold Nanodendrites Enable Synergistic Photodynamic Therapy and NIR Biowindow II Photothermal Therapy and Multimodal Imaging.

Gold nanodendrite (AuND)-based nanotheranostic agents with versatile capabilities were fabricated by optimizing the geometrical configurations (dendrite length and density) of AuND to achieve localized surface plasmon resonance (LSPR) in near-infrared biowindow II (NIR-II), and then subsequently functionalizing with a mitochondria-targeting compound (triphenylphosphonium, TPP), loading with an NIR-photosensitizer (indocyanine green, ICG) and coating with the macrophage cell membrane (MCM) to trap ICG within AuND and selectively interact with MDA-MB-231 cells. The novel AuND-TPP-ICG@MCM system enabled the integration of multimodal fluorescence/photoacoustic/surface-enhanced Raman imaging with synergistic therapies of NIR-II photothermal therapy and NIR-I photodynamic therapy for cancer treatment. Enhanced hyperthermia and elevated production of reactive oxygen species within the tumors via MCM coating and mitochondria targeting afforded a synergistic efficacy for tumor eradication with limited side effects. The demonstrated biocompatibility, multi-imaging capability, and high therapeutic efficiency under NIR laser irradiation indicate the potentials of this multifunctional nanotheranostic platform for clinical utility in cancer therapy.

Antibacterial Activity of Porous Gold Nanocomposites via NIR Light-Triggered Photothermal and Photodynamic Effects.

Phototherapeutic approaches, including photothermal therapy (PTT) and photodynamic therapy (PDT), have become a promising strategy to combat microbial pathogens and tackle the crisis brought about by antibiotic-resistant strains. Herein, porous gold nanoparticles (AuPNs) were synthesized as photothermal agents and loaded with indocyanine green (ICG), a common photosensitizer for PDT, to fabricate a nanosystem presenting near-infrared (NIR) light-triggered synchronous PTT and PDT effects. The AuPNs can not only convert NIR light into heat with a high photothermal conversion efficiency (50.6-68.5%), but also provide a porous structure to facilely load ICG molecules. The adsorption of ICG onto AuPNs was mainly driven by electrostatic and hydrophobic interactions with the surfactant layer of AuPNs, and the aggregate state of ICG significantly enhanced its generation of reactive oxygen species. Moreover, taking advantage of its synergistic PTT and PDT effect, the hybrid nanocomposites displayed a remarkable antibacterial effect to the gram-positive pathogen Staphylococcus aureus (S. aureus) upon 808 nm laser irradiation.

Delicately Designed Cancer Cell Membrane-Camouflaged Nanoparticles for Targeted 19F MR/PA/FL Imaging-Guided Photothermal Therapy.

Our exploration of multimodal nanoprobes aims to combine photoacoustic (PA) imaging, 19F magnetic resonance (MR), and fluorescence (FL) imaging, which offers complementary advantages such as high spatial resolution, unlimited penetration, and high sensitivity to enable more refined images for accurate tumor diagnoses. In this research, perfluorocarbons (PFCs) and indocyanine green (ICG) are encapsulated by poly(lactic-co-glycolic acid) (PLGA) for intravital 19F MR/FL/PA tri-modal imaging-guided photothermal therapy. Then, it is coated with an A549 cancer cell membrane (AM) to fabricate versatile theranostic nanoprobes (AM-PP@ICGNPs). After systemic administration, FLI reveals time-dependent tumor homing of NPs with high sensitivity, 19F MRI provides tumor localization of NPs without background signal interference, and PAI illustrates the detailed distribution of NPs inside the tumor with high spatial resolution. What is more, AM-PP@ICGNPs accumulated in the tumor area exhibit a prominent photothermal effect (48.4 °C) under near infrared (NIR) laser irradiation and realize an enhanced antitumor response in vivo. These benefits, in combination with the excellent biocompatibility, make AM-PP@ICGNPs a potential theranostic nanoagent for accurate tumor localization and ultimately achieve superior cancer therapy.

Cytokine-induced killer cells-assisted tumor-targeting delivery of Her-2 monoclonal antibody-conjugated gold nanostars with NIR photosensitizer for enhanced therapy of cancer.

Maximizing the accumulation of anticancer medicine in the tumor is the priority to achieve minimal invasive cancer therapy, which raises high demands on tumor-targeting ability of drug delivery systems. Herein, we adopted an emerging "cell-drug" strategy via the nanoplatform construction to achieve high aggregation and intratumoral distribution. We fabricated gold nanostars (GNSs) with HER-2 monoclonal antibody (trastuzumab) and near-infrared region (NIR) photosensitizer indocyanine green (ICG) to obtain GNS@ICG-Ab, which combined the photothermal therapy with photodynamic therapy (PTT/PDT) that rely on enhanced photothermal conversion efficiency of GNS and 1O2 generator ICG under the exposure of a NIR laser. Tumor-tropism CIK cells loaded with GNS@ICG-Ab were able to migrate into tumors and make a difference in efficient accumulation and uniform distribution of the GNS@ICG-Ab-CIK nanoplatform inside tumors based on fluorescence, photoacoustic (PA), and computed tomography (CT) imaging observations. Encouraged by the improvements in tumor targeting and retention presented by real-time imaging, we employed the novel nanoplatform to synergistically inhibit the progression of tumors in SK-BR-3 tumor-bearing mice via PTT/PDT and immunotherapy-implemented by CIK cells for activating the immune response, and with the specific linkage between trastuzumab and SK-BR-3 tumor cells, our platform could exert a precise strike of PDT/PTT. Taken together, the integrating tri-modal imaging with tri-modal therapy endows CIK-GNS@ICG-Ab with promising potential in cancer theranostics and lays a solid foundation for the development of immune cell application in nanomedicine delivery.

Biodegradable pH-responsive amorphous calcium carbonate nanoparticles as immunoadjuvants for multimodal imaging and enhanced photoimmunotherapy.

Development of bioresponsive theranostic nanoparticles to enhance cancer diagnostics and control cancer metastasis is highly desirable. In this study, we developed such a bioresponsive theranostic nanoparticle for synergistic photoimmunotherapy. In particular, these nanoparticles were constructed by embedding indocyanine green (ICG) into Mn2+-doped amorphous calcium carbonate (ACC(Mn)) nanoparticles, followed by loading of the Toll-like-receptor-7 agonist imiquimod (IMQ). The IMQ@ACC(Mn)-ICG/PEG nanoparticles respond to the acidic pH of the tumor microenvironment (TME) and co-deliver ICG and IMQ into the tumor. Selective phototherapy was achieved upon activation using a near-infrared laser. In the presence of IMQ and arising from phototherapeutically treated tumor cells, tumor-associated antigens give rise to a strong antitumor immune response. Reversal of the immunosuppressive TME via H+ scavenging of the tumor through ACC nanoparticles effectively inhibits tumor metastases. Moreover, the combination of ICG and Mn2+ also serves as an advanced contrast agent for cancer multimode imaging. Overall, these bioresponsive nanoparticles provide a promising approach for cancer theranostics with promising potential for future clinical translation.

Delivery of MutT homolog 1 inhibitor by functionalized graphene oxide nanoparticles for enhanced chemo-photodynamic therapy triggers cell death in osteosarcoma.

Photodynamic therapy (PDT) generates highly toxic reactive oxygen species (ROS) during noninvasive cancer treatment. MutT homolog 1 (MTH1) protein is a DNA oxidative damage repair protease and suppressing its function may provide a strategy to enhance PDT efficacy by improving cellular sensitivity to ROS. A nanoparticle, composed of functional graphene oxide (GO) conjugated with polyethylene glycol (PEG), folic acid (FA) and photosensitizer indocyanine green (ICG), was constructed to deliver MTH1 inhibitor (TH287) and doxorubicin. The effects of this nanoparticle on biological properties and cell death of osteosarcoma cells were investigated. We further examined the endoplasmic reticulum (ER) stress and apoptosis in osteosarcoma. A xenograft tumor model was used to validate the results in vivo. This drug-carrying PEG-GO-FA/ICG nanoparticle showed combined chemo-photodynamic therapy (Chemo-PDT) to inhibit the proliferation and migration of osteosarcoma cells. Enhanced Chemo-PDT promoted both apoptosis and autophagy by suppressing the MTH1 protein and promoting the accumulation of ROS. In this study, autophagy served as a rescue pathway against cell death, and suppressing autophagy enhanced the anti-cancer effects of Chemo-PDT. However, Chemo-PDT induced apoptosis was related to the occurrence of ER stress. ROS might contribute to ER stress and further induce apoptosis via the JNK/p53/p21 pathway. These findings provide a mechanistic understanding of nanoparticle-induced cell death in osteosarcoma. The combination of Chemo-PDT with other therapies is promising as a new strategy to treat osteosarcoma. STATEMENT OF SIGNIFICANCE: Administration of chemotherapeutic drugs by traditional methods still has many problems. We designed a functionalized graphene oxide drug delivery system to deliver the photosensitizer indocyanine green, doxorubicin, and MTH1 inhibitor TH287. This nano delivery system showed combined chemo-photodynamic effects to inhibit osteosarcoma. Suppressing MTH1 protein might induce "phenotypic lethality" and enhance chemo-photodynamic therapy efficacy by improving cellular sensitivity to reactive oxygen species.

Polylysine modified conjugated polymer nanoparticles loaded with the singlet oxygen probe 1,3-diphenylisobenzofuran and the photosensitizer indocyanine green for use in fluorometric sensing and in photodynamic therapy.

Conjugated polymer hybrid nanoparticles (NPs) loaded with both indocyanine green (ICG) and 1,3-diphenylisobenzofuran (DPBF) are described. The NPs are dually functional in that ICG acts as the photosensitizer, and DPBF as a probe for singlet oxygen (1O2 probe). The nanoparticle core consists of the energy donating host poly(9,9-dioctylfluorenyl-2,7-diyl)-co-(2,5-p-xylene) (PFP). The polymer is doped with the energy acceptor DPBF. Ratiometric fluorometric detection of singlet oxygen is accomplished by measurement of fluorescence at wavelengths of 415 and 458 nm. In addition, the shell of the positively charged polymeric nanoparticles was modified, via electrostatic interaction, with negatively charged PDT drugs ICG. The integrated nanoparticles of type ICG-DPBF-PFP display effective photodynamic performance under 808-nm laser irradiation. The 1O2 sensing behaviors of samples are evaluated based on the ratiometric fluorescent responses produced by DPBF and PFP. 1O2 can be fluorimetically sensed with a detection limit of 28 µM. The multifunctional nanoprobes exhibit effortless cellular uptake, superior photodynamic activity and a rapid ratiometric response to 1O2. Graphical abstractSchematic of a dual-functional nanoplatform for photodynamic therapy (PDT) and singlet oxygen (1O2) feedback. It offers a new strategy for self-monitoring photodynamic ablation. FRET: fluorescence resonance energy transfer. Indocyanine green is attached in the shell of nanoparticles, and 1,3-diphenylisobenzofuran is doped into the energy donating host conjugated polymer.

Tracing the molecular dynamics of living mitochondria under phototherapy via surface-enhanced Raman scattering spectroscopy.

Subcellular mitochondrion has become a target for improving the therapeutic efficiency and reducing side damage to normal cells via a combination of many therapeutic strategies. However, the underlying molecular mechanisms associated with cell death induced by subcellular dysfunction remain unknown or disputed. In this study, we investigated the dynamic molecular changes of living mitochondria upon phototherapy (photothermal therapy plus photodynamic therapy, PTT & PDT) by surface-enhanced Raman scattering spectroscopy (SERS) and intended to disclose the photo-induced cell death route in breast cancer cells (MCF-7) taking into account the mitochondrion. Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved clinic blood-injection near-infrared angiographic contrast agent and a PTT & PDT drug, was used for the evaluation of the phototherapy effect. The results revealed that the content of phenylalanine (Phe) in mitochondria evidently increased during the phototherapy-induced cell death process. Moreover, the phototherapy-induced cell apoptosis was mainly regulated through the DNA structures. We expect that the understanding of mitochondrial molecular stress responses will be helpful for the diagnosis and therapy of cellular processes associated with mitochondria and provide valuable guidance for the further design and development of more effective therapeutic platforms and methods at the sub-cellular level.

Gallium-68-Labelled Indocyanine Green as a Potential Liver Reserve Imaging Agent.

Objective: This work evaluated the potential of 68Ga-labelledNOTA-ICG (1,4,7-triazacyclononane-1,4,7-triacetic acid indocyanine green) for liver reserve imaging. Methods: To determine the optimal conditions for generating 68Ga-NOTA-ICG, various reaction parameters were implemented. Quality control analysis was performed using different chromatography techniques. The in vitro and in vivo stability was also measured at specific time points. The radioactivity ratio between n-octanol and water was determined to evaluate the water solubility of 68Ga-NOTA-ICG. The plasma-protein binding rate of the labelled compound was determined by the methanol method. The biodistribution and imaging findings were evaluated in normal animals at different time points after injection. A preliminary imaging evaluation was performed using an animal model of hepatic ischaemia-reperfusion injury, which was confirmed by pathology. Results: 68Ga-NOTA-ICG was prepared with very high radiochemical purity (>98%) by reacting at 90°C for 10 min at pH = 3.5∼4.0, with excellent stability in vivo and in vitro (>95% 3 h postpreparation). The in vitro plasma-protein binding rate of 68Ga-NOTA-ICG was 13.01 ± 0.7%, and it showed strong water solubility (log P=-2.01 ± 0.04). We found that in addition to excretion through the biliary tract and intestines, 68Ga-NOTA-ICG can be excreted through the urinary tract. The image quality of 68Ga-NOTA-ICG was very high; imaging agent retained in the area of liver injury could clearly be observed. Conclusion: This is the first report on a 68Ga-labelled NOTA-ICG fragment for liver reserve function studies. This complex has promise as a candidate agent for liver reserve imaging.

State-of-the-Art Preclinical Photoacoustic Imaging in Oncology: Recent Advances in Cancer Theranostics.

The optical imaging plays an increasing role in preclinical studies, particularly in cancer biology. The combined ultrasound and optical imaging, named photoacoustic imaging (PAI), is an emerging hybrid technique for real-time molecular imaging in preclinical research and recently expanding into clinical setting. PAI can be performed using endogenous contrast, particularly from oxygenated and deoxygenated hemoglobin and melanin, or exogenous contrast agents, sometimes targeted for specific biomarkers, providing comprehensive morphofunctional and molecular information on tumor microenvironment. Overall, PAI has revealed notable opportunities to improve knowledge on tumor pathophysiology and on the biological mechanisms underlying therapy. The aim of this review is to introduce the principles of PAI and to provide a brief overview of current PAI applications in preclinical research, highlighting also on recent advances in clinical translation for cancer diagnosis, staging, and therapy.

Development of Multifunctional Polydopamine Nanoparticles As a Theranostic Nanoplatform against Cancer Cells.

Although demanding, the development of multifunctional theranostic nanoplatforms is attracting considerable worldwide interest. Herein, a theranostic nanoplatform with multifunctions based on polydopamine (PDA) nanoparticles (NPs) was developed, owning dual-imaging and dual-therapy functions for cancer theranostic applications. PDA NPs were generated using a facile polymerization method under alkaline conditions, followed by poly(ethylene glycol) (PEG) modification. Then, the obtained NPs were loaded with IR820 and Fe3+ ions to produce the final PEGylated PDA/IR820/Fe3+ (PPIF) NPs. The PPIF NPs thus generated displayed increasingly brighter photoacoustic and magnetic resonance signals with increasing NP concentration and were demonstrated to be cytocompatible and effectively taken up and internalized into HeLa cells. Under near-infrared light irradiation, PPIF NPs can produce heat and reactive oxygen species for photothermal/photodynamic combined cancer therapy. In this study, the versatility of PDA NPs was demonstrated to be promising as a multifunctional nanoplatform for potential cancer theranostic applications.

Ultrahigh Sensitivity Multifunctional Nanoprobe for the Detection of Hydroxyl Radical and Evaluation of Heavy Metal Induced Oxidative Stress in Live Hepatocyte.

Hydroxyl radical (•OH) is an important marker of the progress of heavy metal induced oxidative stress. However, most reported probes and detection methods cannot meet the need of monitoring the •OH concentration within the whole progress because of the limited linear range. Besides, a low detection limit, high sensitivity, and good selectivity were also required. In this study, an ultrahigh sensitivity multifunctional nanoprobe (ICG-modified NaLuF4:Yb,Er) was developed to evaluate heavy metal induced oxidative stress by detecting •OH concentration, with a colorimetric, upconversion luminescence, and photothermal stepped method. This method has a broad linear detection range, from 16 pM to 2 µM, and a low detection limit of 4 pM. Besides, the nanoprobe showed less response to ions, amino acids, biomolecules, and other radical oxygen species (H2O2 and O2-) than •OH. This highly selective, highly sensitive probe with a broad linear detection range has great potential utility for monitoring •OH concentration in live hypatocyte within the progress of heavy metal induced oxidative stress, with probable in vivo applications in the future.

Biochemical analysis and decomposition products of indocyanine green in relation to solvents, dye concentrations and laser exposure.

PURPOSE: To investigate pH, ions, osmolarity and precipitation of indocyanine green (ICG), as well as the profile of ICG decomposition products (DPs) after laser exposure and the interaction with quenchers. METHODS: ICG was diluted in water, 5% glucose (GL) or balanced salt solution (BSS) to achieve concentrations of 2.5, 1, 0.25 and 0.1 mg/ml. Osmolarity, pH and precipitation were analyzed immediately and after 24 h. Precipitation analyses were done with a scanning electron microscope. Anion and iodate analyses of ICG and infracyanine green (IfCG) were performed by capillary zone electrophoresis. With regard to DPs, 0.5 mg/ml of ICG was assessed with high-performance liquid chromatography (HPLC) after 810-nm laser irradiation. DP profiles were evaluated with ICG dilution in quenchers (Trolox, histidine and DABCO) in 3 concentrations (0.1, 1 and 10 M). RESULTS: BSS promoted iso-osmotic ICG solutions of 208 mOsm (147-266) compared to GL with 177 mOsm. BSS solutions had a higher physiological pH of 7.2 compared with the GL one of 6.55. ICG precipitated more when diluted with BSS (5.95 mg); in contrast, GL showed less precipitate (3.6 mg). IfCG has no iodine derivates and other ICGs have an average 4.6% of iodate derivates. From HPLC analysis, 5 DPs were observed. The rate of DPs was higher when BSS was used (p < 0.05). Five DPs have been generated with ICG, and they may be altered with the quenchers DABCO, histidine and Trolox. CONCLUSIONS: BSS dilution induces more precipitation and DPs. ICG dilution in any solvent induces DPs. Quencher use reduces the amount of toxic DPs.

Antimicrobial properties of light-activated polyurethane containing indocyanine green.

The aim of this study was to produce novel antimicrobial polymers containing the light-activated antimicrobial agent indocyanine green (ICG). The novel materials were prepared by swelling polyurethane in acetone containing water and ICG, followed by solvent evaporation. The uptake of ICG was dependent upon the ratio of acetone to water. Only at a ratio of 99 parts acetone to 1 part water was there any substantial colouration of the samples. When exposed to laser light from the near infrared spectrum (808 nm), polyurethane-containing ICG exhibited antimicrobial activity against Gram-positive bacteria; a 2 log10 reduction was achieved against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis after 15 min exposure, corresponding to an energy dose of 31.83 J delivered at an energy density of 31.83 J/cm². Under the same conditions, Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) appeared to be less susceptible, the viable count being reduced by 0.5 log10. Some of the physical properties of the resulting material were also investigated and it was found that the elasticity (Young's modulus) was reduced by approximately 60%. Furthermore, when the ICG-containing polymer was stretched, the breaking point occurred when the elongation was 6.7 times the initial value, while ICG-free polyurethane samples did not break following a 7-fold elongation. The contact angles for water droplets revealed that the ICG-containing polymer was more hydrophobic than untreated polyurethane. The results of this study show that ICG can be embedded in polyurethane to produce materials which when irradiated with near-infrared light can exert a bactericidal effect particularly against MRSA and S. epidermidis. Such materials may be useful for preparing intravenous catheters, which are often colonized by such organisms.

Temperature distribution during ICG-dye-enhanced laser photocoagulation of feeder vessels in treatment of AMD-related choroidal neovascularization.

Laser photocoagulation of the feeder vessels of age-related macula degeneration-related choroidal neovascularization (CNV) membranes is a compelling treatment modality, one important reason being that the treatment site is removed from the fovea in cases of sub- or juxtafoveal CNV. To enhance the energy absorption in a target feeder vessel, an indocyanine green dye bolus is injected intravenously, and the 805 nm wavelength diode laser beam is applied when the dye bolus transits the feeder vessel; this tends to reduce concomitant damage to adjacent tissue. A 3D theoretical simulation, using the Pennes bioheat equation, was performed to study the temperature distribution in the choroidal feeder vessel and its vicinity during laser photocoagulation. The results indicate that temperature elevation in the target feeder vessel increases by 20% in dye-enhanced photocoagulation, compared to just photocoagulation alone. The dye bolus not only increases the laser energy absorption in the feeder vessel but also shifts the epicenter of maximum temperature away from the sensitive sensory retina and retinal pigment epithelial layers and toward the feeder vessel. Two dominant factors in temperature elevation of the feeder vessel are location of the feeder vessel and blood flow velocity through it. Feeder vessel temperature elevation becomes smaller as distance between it and the choriocapillaris layer increases. The cooling effect of blood flow through the feeder vessel can reduce the temperature elevation by up to 21% of the maximum that could be produced. Calculations were also performed to examine the effect of the size of the laser spot. To achieve the same temperature elevation in the feeder vessel when the laser spot diameter is doubled, the laser power level has to be increased by only 60%. In addition, our results have suggested that more studies are needed to measure the constants in the Arrhenius integral for assessing thermal damage in various tissues.

Light-induced decomposition of indocyanine green.

PURPOSE: To investigate the light-induced decomposition of indocyanine green (ICG) and to test the cytotoxicity of light-induced ICG decomposition products. METHODS: ICG in solution was irradiated with laser light, solar light, or surgical endolight. The light-induced decomposition of ICG was analyzed by high-performance liquid chromatography (HPLC) and mass spectrometry. Porcine retinal pigment epithelial (RPE) cells were incubated with the light-induced decomposition products of ICG, and cell viability was measured by trypan blue exclusion assay. RESULTS: Independent of the light source used, singlet oxygen (photodynamic type 2 reaction) is generated by ICG leading to dioxetanes by [2+2]-cycloaddition of singlet oxygen. These dioxetanes thermally decompose into several carbonyl compounds. The decomposition products were identified by mass spectrometry. The decomposition of ICG was inhibited by adding sodium azide, a quencher of singlet oxygen. Incubation with ICG decomposition products significantly reduced the viability of RPE cells in contrast to control cells. CONCLUSIONS: ICG is decomposed by light within a self-sensitized photo oxidation. The decomposition products reduce the viability of RPE cells in vitro. The toxic effects of decomposed ICG should be further investigated under in vivo conditions.

Stability assessment of indocyanine green within dextran-coated mesocapsules by absorbance spectroscopy.

The biocompatibility and high absorption in the near IR range of indocyanine green (ICG) have made it a suitable candidate chromophore for optical imaging and laser-mediated therapy of superficial tumors. However, its clinical efficacy remains limited by factors such as rapid circulation kinetics, lack of target specificity, and molecular instability. Such drawbacks motivated us to encapsulate ICG into carrier particles to improve target specificity and retention time. We use absorbance spectroscopy to investigate the effects of encapsulating ICG within dextran-coated capsules. The mesocapsules (MCs) containing ICG are synthesized using a previously reported charge-assembly technique. Both freely dissolved ICG and ICG-MCs are prepared with ICG concentrations of either 50 or 10 microg/ml. Samples are exposed either to a broadband light source or incubated at 3, 23, or 40 degrees C. Absorbance spectra are recorded at various time points up to 96 h. At the lower concentration of 10 microg/ml, ICG within MCs experiences less light-induced degradation. The MC system also protects ICG from thermal degradation at all tested temperatures. The polymer-salt aggregate core of the MCs hinders the mobility of ICG molecules. The MC system shields ICG from vibrational and translational agitation as well as molecular changes such as fragmentation.