Near-infrared Laser Exposure Research Articles

Defect engineering synergistically boosts the catalytic activity of Fe-MoOv for highly efficient breast mesh antitumor therapy

The demand for breast mesh with antitumor properties is critical in post-mastectomy breast reconstruction to prevent local tumor recurrence. Molybdenum-based oxide (MoOx) exhibits enzyme-like activities by catalyzing endogenous hydrogen peroxide to produce reactive oxygen species for inducing tumor cell apoptosis. However, its catalytic activity is limited by insufficient active sites. Herein, a defect engineering strategy is proposed to create redox nanozymes with multiple enzymatic activities by incorporating Fe into MoOx (Fe-MoOv). Fe-MoOv is subsequently integrated into polycaprolactone (PCL) to fabricate breast meshes for establishing an enzyme-catalyzed antitumor platform. The doping of Fe into MoOx formed numerous defect sites, including oxygen vacancies (OV) and Fe substitution sites, synergistically boosting the binding capacity and catalytic activity of Fe-MoOv. Density functional theory calculations demonstrated that the outstanding peroxidase-like catalytic activity of Fe-MoOv resulted from the synergy between OV and Fe sites. Additionally, OV contributes to the localized surface plasmon resonance effect, enhancing the photothermal capability of the PCL/Fe-MoOv mesh. Upon near-infrared laser exposure, the catalytic activity of the PCL/Fe-MoOv mesh is further improved, leading to increased generation of reactive oxygen species and enhanced antitumor efficacy, achieving 86.7% tumor cell mortality, a 264% enhancement compared to the PCL/MoOx mesh.

Pd octahedra nanocubes mediated photo-fenton catalytic performance for sustainable degradation of methylene blue

This research utilized a typical solvothermal approach, by employing Na2PdCl4 as the synthetic precursor, L-ascorbic acid (AA) as the reductant agent, and polyvinylpyrrolidone (PVP) as the practical surfactant, palladium (Pd) octahedra was finally effectively synthesized by the hydrothermal and solvothermal methods. Subsequently, characterizations of Pd octahedra were conducted by using TEM, XPS, XRD, and other analytical methods. Whereafter, Pd octahedra displayed a consistent shape and size, featuring a distinctive tip-shaped structure, which conferred upon them outstanding optical absorption properties within the near-infrared (NIR) region. Consequently, under NIR laser exposure, Pd octahedra could elevate local reaction temperature via in-situ photothermal conversion, thereby stimulating the formation of active sites of Fenton catalysts. The Photo-Fenton catalytic activity of Pd octahedra was investigated by using methylene blue (MB) as a model pollutant. The degradation efficiency of MB reached 94.8 % within 35 min under 808 nm laser irradiation, and the removal rate of MB by Pd octahedra could still reach more than 90 % after five cycles of use. All the results manifest that Pd octahedra exhibit excellent purification performance for MB dyestuff wastewater.

Engineering an Organic Nanoplatform for Augmented Pyroeletroimmunotherapy.

Photothermal immunotherapy has shown great promise in the treatment of tumor metastasis. However, the thermal resistance of tumor cells substantially compromises the treatment effect of photothermal immunotherapy. Herein, a high-performance organic pyroelectric nanoplatform, tBu-TPAD-BF2 nanoparticles (NPs), is rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible tBu-TPAD-BF2 NPs with excellent pyroelectric and photothermal conversion properties are constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with tBu-TPAD-BF2 NPs causes an apparent temperature elevation upon near-infrared (NIR) laser irradiation, inducing potent immunogenic cell death (ICD). Additionally, the temperature variations under alternating NIR laser irradiation facilitate reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrate that tBu-TPAD-BF2 NPs in combination with NIR laser exposure notably inhibit primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling reveals that treatment with tBu-TPAD-BF2 NPs markedly suppresses metastasis under NIR laser illumination by downregulating metastasis-related genes and upregulating immune response-associated pathways. Therefore, this study provides a strategy for designing high-performance pyroelectric nanoplatforms to effectively cure tumor metastasis, thereby overcoming the inherent shortcomings of photothermal immunotherapy.

Catalytic Dual-Mode Immunotherapy: Anisotropic AuPt Heterostructure Decorated with Starry Pt Nanoclusters for Robust Cancer Photometalloimmunotherapy.

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.

Hydrogel design to overcome thermal resistance and ROS detoxification in photothermal and photodynamic therapy of cancer

Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (−)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.

Redirecting Antigens by Engineered Photosynthetic Bacteria and Derived Outer Membrane Vesicles for Enhanced Cancer Immunotherapy.

Significant strides have been made in the development of cancer vaccines to combat malignant tumors. However, the natural immunosuppressive environment within tumors, known as the tumor microenvironment (TME), hampers the uptake and presentation of antigens by antigen-presenting cells (APCs) within the tumor itself. This limitation results in inadequate activation of immune responses against cancer. In contrast, immune cells in peritumoral tissue maintain their normal functions. In this context, we present an interesting approach to enhance cancer immunotherapy by utilizing engineered photosynthetic bacteria (PSB) and their outer membrane vesicles (OMVPSB) to capture and transport antigens to the outer regions of the tumor. We modified PSB with maleimide (PSB-MAL), which, when exposed to near-infrared (NIR) laser-mediated photothermal therapy (PTT), induced extensive cancer cell death and the release of tumor antigens. Subsequently, the NIR-phototactic PSB-MAL transported these tumor antigens to the peripheral regions of the tumor under NIR laser exposure. Even more intriguingly, PSB-MAL-derived OMVPSB-MAL effectively captured and delivered antigens to tumor-draining lymph nodes (TDLNs). This facilitated enhanced antigen presentation by mature and fully functional APCs in the TDLNs. This intricate communication network between PSB-MAL, the OMVPSB-MAL, and APCs promoted the efficient presentation of tumor antigens in the tumor periphery and TDLNs. Consequently, there was a notable increase in the infiltration of cytotoxic T lymphocytes (CTLs) into the tumor, triggering potent antitumor immune responses in both melanoma and breast cancer models. This cascade of events resulted in enhanced suppression of tumor metastasis and recurrence, underscoring the robust efficacy of our approach. Our interesting study, harnessing the potential of bacteria and OMVs to redirect tumor antigens for enhanced cancer immunotherapy, provides a promising path toward the development of personalized cancer vaccination strategies.

MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.

Development and characterization of pH-responsive nanocarriers for chemo-photothermal combination therapy of acidic tumors.

The combination of photothermal therapy and chemotherapy has been considered a promising strategy for improving the excellent antitumor activities of these treatments. In this study, we developed a new simple type of pH-sensitive chemo-photothermal combination agent capable of repeated exposures to a near-infrared (NIR) laser and evaluated its anticancer efficacy in vitro and in vivo. Doxorubicin (Dox) and gold nanoclusters (GNCs) were successfully co-loaded into pH-sensitive nanoparticles (poly(ethylene glycol)-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl)imidazole-L-aspartamide)] (PEG-PABI)), resulting in a particle size of approximately120 nm with a narrow size distribution. The dual drug-loaded nanoparticles (Dox/GNC-loaded PEG-PABI micelles (Dox/GNC-Ms)) showed consistent pH-sensitive properties and heat generation efficiency after repeated NIR laser exposure. In particular, GNC-M has improved photothermal stability while maintaining high photothermal conversion efficiency, addressing the shortcomings of previous gold nanoparticles. As the concentration of GNC-Ms, irradiation light exposure time, and light source intensity increased, the amount of heat generated and the anticancer effect increased. When Dox was encapsulated with GNCs (Dox/GNC-Ms), a faster drug release rate under acidic pH conditions and a strong synergistic effect against U87MG cells were observed. When the Dox/GNC-M system was extended to in vivo studies, it effectively increased the temperature of the tumor tissue under near-infrared irradiation and showed excellent anticancer efficacy. Therefore, the Dox/GNC-M system could be a simple but promising strategy for chemo-photothermal combination treatment capable of targeting acidic tumors.

Potential of Gold Nanoparticles for Noninvasive Imaging and Therapy for Vascular Inflammation

PurposeMacrophages contribute to the progression of vascular inflammation, making them useful targets for imaging and treatment of vascular diseases. Gold nanoparticles (GNPs) are useful as computed tomography (CT) contrast agents and light absorbers in photothermal therapy. In this study, we aimed to assess the viability of macrophages incubated with GNPs after near-infrared (NIR) laser light exposure and to evaluate the utility of intravenously injected GNPs for in vivo imaging of vascular inflammation in mice using micro-CT.ProceduresMouse macrophage cells (RAW 264.7) were incubated with GNPs and assessed for GNP cellular uptake and cell viability before and after exposure to NIR laser light. For in vivo imaging, macrophage-rich atherosclerotic lesions were induced by carotid ligation in hyperlipidemic and diabetic FVB mice (n = 9). Abdominal aortic aneurysms (AAAs) were created by angiotensin II infusion in ApoE-deficient mice (n = 9). These mice were scanned with a micro-CT imaging system before and after the intravenous injection of GNPs.ResultsThe CT attenuation values of macrophages incubated with GNPs were significantly higher than those of cells incubated without GNPs (p < 0.04). Macrophages incubated with and without GNPs showed similar viability. The viability of macrophages incubated with GNPs (100 μg/ml or 200 μg/ml) was decreased by high-intensity NIR laser exposure but not by low-intensity NIR laser exposure. In vivo CT images showed higher CT attenuation values in diseased carotid arteries than in non-diseased contralateral arteries, although the difference was not statistically significant. The CT attenuation values of the perivascular area in AAAs of mice injected with GNPs were significantly higher than those of mice without injection (p = 0.0001).ConclusionsMacrophages with GNPs had reduced viability upon NIR laser exposure. GNPs intravenously injected into mice accumulated in sites of vascular inflammation, allowing detection of carotid atherosclerosis and AAAs in CT imaging. Thus, GNPs have potential as multifunctional biologically compatible particles for the detection and therapy of vascular inflammation.

Computational modeling and damage threshold prediction of continuous-wave and multiple-pulse porcine skin laser exposures at 1070 nm

Computational models are capable of simulating the expected thermal response of biological tissue to laser irradiation. A typical laser tissue model accounts for optical energy deposition, heat transfer, and damage assessment, with the latter often represented by calculation of the Arrhenius integral. Previous studies have successfully employed these methods to predict skin damage thresholds at laser wavelengths with high absorption in water, and usually for single continuous-wave exposures. However, there remains a need for a robust and accurate predictive model in low-absorption, high-scattering cases, such as for exposures in the near-infrared region near 1000 nm. This study presents a framework for modeling laser irradiation of skin tissue at 1070 nm for both continuous-wave and pulsed exposures with durations ranging from 10−2 to 101 s. The authors derive an optical absorption coefficient for the epidermis that agrees with expected chromophore distribution and report the modeled skin thermal responses alongside surface thermography data from in vivo porcine exposures as validation of simulation accuracy. Comparisons of modeled damage thresholds calculated by the Arrhenius integral with documented experimentally determined minimum visible lesion ED50 data exhibit a high degree of agreement. The authors also provide new Arrhenius rate process coefficients of A = 2.74 × 1094 s−1 and Ea = 5.90 × 105 J/mol, determined from experimental thermal profiles with a unique method, that demonstrate more accurate threshold predictions than those used in previous modeling studies. The techniques outlined by this study provide a useful tool in assessing potentially hazardous near-infrared laser exposure scenarios.

NIR-sensitized cationic frontal polymerization of vinyl ether and epoxy monomers

Radical Induced Cationic frontal polymerization (RICFP) of vinyl ethers and epoxides with Near-Infrared (NIR) sensitizer has been scarcely reported in the literature. In this paper, a two-component system including cyanine as NIR sensitizer and iodonium salt as co-initiator was employed to initiate the polymerization of cationic polymerizable monomers upon 808 nm NIR laser exposure. The activities of cationic polymerizable monomers like viny ethers, epoxides, and oxetanes were studied using the NIR initiating system aforementioned. The aryl glycidyl ethers (E51) and vinyl ethers exhibited higher conversion than cycloaliphatic epoxide (6110) and oxetane (GR43). Additionally, a three-component system comprising NIR sensitizer, iodonium salt and thermal initiator was investigated on RICFP. Vinyl ethers showed the highest reactivity, whose velocity can reach to 2.5 cm s−1 compared to other kinds of cationic polymerizable monomers. Compared with other thermal initiators, AIBN could promote the RICFP of vinyl ethers. But when the monomers turned to E51 and GR43, AIBN could not work on RICFP. Meanwhile, another thermal initiator (1, 1, 2, 2- tetraphenylethanediol) carrying a C–C labile showed acceptable reactivity on RICFP.

Optimization of the Preparation of Magnetic Liposomes for the Combined Use of Magnetic Hyperthermia and Photothermia in Dual Magneto-Photothermal Cancer Therapy

In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)–photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF–NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH–PT dual magneto-photothermal cancer therapy.

Near-infrared light and glucose dual-responsive cascading hydroxyl radical generation for in situ gelation and effective breast cancer treatment

A general therapeutic strategy to treat breast cancer is attractive as different subtypes of breast cancers often exhibit distinct response to existing cancer therapeutics. To this end, we prepare a catalyst couple of glucose oxidase (GOx) and gallic acid-ferrous (GA-Fe) nanocomplexes, a type of near-infrared (NIR) absorbing Fenton catalyst, to enable NIR-trigger in-situ gelation and enhanced chemodynamic/starvation therapy that appears to be effective for different types of breast cancer cells. In this system, GOx is mixed with GA-Fe in a solution of N,N-dimethylacrylamide (DMAA) and poly (ethylene glycol) double acrylate (PEGDA). Upon intratumoral injection and NIR laser exposure, such GA-Fe show rapid temperature increase, which would simultaneously increase the catalytic efficiencies of GA-Fe and GOx. The cascade production of hydroxyl radicals (•OH) from glucose is then initiated to enable polymerization of DMAA and PEGDA to form a hydrogel at the injection site within the tumor. The continuous production of cytotoxic •OH together with glucose depletion by the intratumorally fixed catalyst couple would further confer effective destruction of breast cancer tumors by such chemodynamic/starvation therapy. Our work presents a hydrogel-based therapeutic strategy for local treatment of solid tumors with high tumor destruction efficacy and low systemic toxicity.

Abstract B040: Electrospun implantable anticancer device comprising immune adjuvant photo-responsive nanoparticles with checkpoint blockade for effective cancer therapy

Abstract An implantable anticancer device (IAD) that can eradicate local regional breast cancer recurrence (LRR), inhibit metastasis as well as to enhance the breast reconstruction during/after therapy is proposed. The IAD is developed by combining nanofiber-based chemo-photothermal therapy platform with check point blockade immunotherapy. Here we developed a coreshell electrospun nanofiber encapsulated with drug conjugated MoS2 as chemo-photothermal agent along with imiquimod as an immune response modifier. The near-infrared laser exposure to IADs can generate tumor-associated antigens from primary tumors, which in the presence of released imiquimod from IADs can show vaccine-like functions. Moreover, the nanofiber matrix will enable the sustained and tumor-specific anticancer drug release with a minimum initial burst release and the repeated photothermal capability to ensure the synergistic inhibition of tumor recurrence. In addition to that, the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4) in combination with the generated immunologic responses will be able to attack remaining tumor cells causing metastasis inhibition with strong immunologic memory effect, which can shield against the tumor recurrence after the post elimination of initial tumors. The IAD nanofiber morphology resembles the extra cellular matrix (ECM) enrich the reconstruction of poor breast cosmesis resulted from the surgical treatment, by supporting the lipofilling of the surgical residual cavity to induce the adipogenic process. So, in this work we propose that the tumor associated antigens created in situ after photothermal therapy by the immune adjuvant nanofiber IAD could show vaccine-like functions, which in combination with checkpoint blockade show strong antitumor immune responses for effective cancer immunotherapy as a potential platform for synergistic inhibition of LRR and a great promise for the in situ breast reconstruction ability for better breast cosmesis. Citation Format: Afeesh Rajan Unnithan, Arathyram Ramachandra Kururp Sasikala, Chan Hee Park, Cheol Sang Kim. Electrospun implantable anticancer device comprising immune adjuvant photo-responsive nanoparticles with checkpoint blockade for effective cancer therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B040.

Near‐Infrared Laser‐Triggered Nitric Oxide Nanogenerators for the Reversal of Multidrug Resistance in Cancer

The potential therapeutic implications of nitric oxide (NO) for diverse diseases have been under consideration for years; however, the development of precisely controllable NO generation system with potential for clinical application has remained elusive. Herein, intelligent near‐infrared (NIR) laser‐triggered NO nanogenerators for the treatment of multidrug‐resistant (MDR) cancer are fabricated by integrating photothermal agents and heat‐sensitive NO donors into a single nanoparticle. Such nanogenerators can absorb 808 nm NIR photons and convert them into ample heat to trigger NO release. The generated NO molecules are demonstrated to successfully achieve multidrug‐resistance reversal by inhibiting the expression of P‐glycol protein. Consequently, the intracellular accumulation of doxorubicin is effectively increased, resulting in high toxicity to MDR cancer cells in vitro. By virtue of surface modification with targeting ligands, these nanoparticles are able to selectively accumulate in tumor tissue. The therapeutic effects of the nanogenerators are validated in a humanized MDR cancer model. The in vivo experiment indicates that the nanoparticles possess excellent tumor suppression functionality with few side effects upon NIR laser exposure. Therefore, this novel photothermal conversion‐based NO‐releasing platform is expected to be a potential alternative to clinical MDR cancer treatment and may provide insights with regard to other NO‐relevant medical treatments.

Selective Photothermal Tumor Therapy Using Nanodiamond‐Based Nanoclusters with Folic Acid

This paper describes the fabrication and evaluation of folic acid (FA)‐conjugated nanodiamond (ND) nanoclusters for selective photothermal tumor therapy. ND nanoclusters with surface carboxyl groups are aminated using ethylenediamine and conjugated with FA via carbodiimide chemistry. The temperature of an aqueous ND dispersion (10 μg mL−1) is increased to 54 °C upon laser exposure for 5 min. FA‐ND nanoclusters are preferentially taken up by KB cells (folate receptor positive) compared to WI‐38 (folate receptor negative) cells, suggesting specificity for tumor cells that overexpress folate receptors. Cell viability tests reveal that FA‐ND nanoclusters effectively and selectively ablate KB cells upon near‐infrared (NIR) laser exposure. In addition, fluorescence microscopy images confirm that only KB cells treated with FA‐ND nanoclusters are ablated in a spot (200 μm in diameter) by NIR laser exposure. In an animal model, a large amount of FA‐ND nanoclusters is accumulated into tumor tissue, resulting in dramatically reduced tumor volume post‐NIR laser exposure as compared to ND nanoclusters.

Abstract 3903: Optimizing the antitumor efficacy of AuNR-assisted plasmonic photothermal therapy and its molecular impact

Abstract Plasmonic gold nanorods (AuNRs) are very promising for biomedical applications because of their strongly enhanced radiation (e.g. absorption and scattering) and non-radioactive photothermal properties due to surface plasmon resonance. In plasmonic photothermal therapy (PPTT), AuNRs absorb near infrared (NIR) laser and induce localized heat (i.e., hyperthermia) which can promote tumor tissue ablation. However, the lack of comprehensive studies to improve the efficiency of AuNRs has hindered their application. The objectives of this study were to perform a systematic analysis to optimize AuNR-PPTT based on different sizes, formulation and concentration along with various laser powers for cancer therapy in vitro and in vivo. We used AuNRs of sizes 26×6 nm and 72×19 nm with concentrations of 2.5, 5 and 10 nM, followed by 2 min of 0.5, 1, 1.78 W/cm2 NIR 808 nm diode laser exposure both in vitro and in vivo. For in vitro studies, we studied several head and neck squamous cell carcinoma (HNSCC) cell lines. We conducted an in vivo antitumor efficacy study in nude mice bearing human HNSCC Tu686 xenograft tumors with three formulations of AuNRs (72×19 nm and 26×6 nm with or without rifampicin (Rf) conjugation).Single dose intratumoral injection of 5 nM and 10 nM AuNRs (26×6 nm), followed by 2 min of 1.78 W/cm2 NIR laser exposure inhibited tumor growth and the 2.5 nM dose led to moderate antitumor efficacy. However, we observed severe skin burning at higher concentrations. In contrast, AuNRs (72×19nm) had no remarkable antitumor efficacy at high laser power. Impressively, small AuNR-conjugated Rf (AuNR-Rf) accumulated AuNRs inside the cell and had very significant antitumor efficacy (p&amp;lt;0.05) without any skin burning at 2.5 nM concentration. We confirmed our observations by immunohistochemistry staining of proliferation marker Ki67 in tumor tissues. To understand the molecular impact, we applied the optimized treatment in vitro. AuNR-Rf was able to induce apoptosis in 24 hours of treatment and decreased cell viability, as supported by immunoblotting of PARP and caspase 3 cleavage. In addition, we found that mutant p53 was completely abolished in AuNR-PPTT treatment. Overall, we have demonstrated that 2.5 nM AuNR with 1.78 W/cm2 NIR laser has no remarkable toxicities and optimal antitumor efficacy was observed by conjugation with Rf. In future studies, we will explore potential novel biomarkers by next generation sequencing (NGS) in mouse tumor tissues to determine the response to AuNR-PPTT. (This study supported by U01CA151802). [M.A.R. and M.R.K.A. contributed equally to this work.] Citation Format: Mohammad Aminur Rahman, Moustafa R. K. Ali, Zhixiang Zhao, Georgia Z. Chen, Mostafa A. El-Sayed, Dong M. Shin. Optimizing the antitumor efficacy of AuNR-assisted plasmonic photothermal therapy and its molecular impact. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3903.

Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.

Laser Exposure of Dry Aqueous Ink for Continuous-Feed High-Speed Inkjet Printing

Inkjet printing using water-based pigment ink has been carried out with laser exposure to dry the ink in a short period of time (approximately the same as the penetration time). Heating by near-infrared laser exposure is advantageous because it heats only the ink without heating the paper. As a result, the formation of cockles or creases in the paper is suppressed, and the optical density of printed images is improved. In addition, show-through to the back side of the paper is reduced, and bleeding is also suppressed. Furthermore, it is demonstrated that the favorable conditions for laser exposure are different on different types of paper because of the different penetration times; the mechanisms of the penetration and the drying are also discussed.

Photofunctional nanomodulators for bioexcitation.

A single organism comprises diverse types of cells. To acquire a detailed understanding of the biological functions of each cell, comprehensive control and analysis of homeostatic processes at the single-cell level are required. In this study, we develop a new type of light-driven nanomodulator comprising dye-functionalized carbon nanohorns (CNHs) that generate heat and reactive oxygen species under biologically transparent near-infrared (NIR) laser irradiation. By exploiting the physicochemical properties of the nanohorns, cellular calcium ion flux and membrane currents were successfully controlled at the single-cell level. In addition, the nanomodulator allows a remote bioexcitation of tissues during NIR laser exposure making this system a powerful tool for single-cell analyses and innovative cell therapies.