Light-Responsive Nanomaterials for Cancer Therapy

Due to its unique advantages,which include minimal invasiveness and relative clinical safety,photother-apy is considered to be a promising approach for cancer treatment.However,the treatment efficacy of phototherapy is often restricted by the limited depth of light penetration and the low targeting effect of phototherapeutic agents.The emergence of light-responsive nanomaterials offers a possible approach to achieve enhanced phototherapy potency.This review summarizes the progress in biomedical applica-tions of light-responsive nanomaterials for cancer therapy,which include photothermal therapy(PTT),photodynamic therapy(PDT),light-responsive molecule delivery,and light-controlled combination ther-apy.Future prospects are also discussed.This review aims to demonstrate the significance of light-responsive nanomaterials in cancer therapy and to provide strategies to expand the applications of phototherapy.

Visible Light-Responsive N-Doped TiO_(2) Photocatalysis:Synthesis,Characterizations,and Applications

Photocatalysis based on semiconductors has recently been receiving considerable research interest because of its extensive applications in environmental remediation and renewable energy generation.Various semiconductor-based materials that are vital to solar energy utilization have been extensively investigated,among which titanium oxide(TiO_(2))has attracted considerable attention because of its exceptional physicochemical characteristics.However,the sluggish responsiveness to visible light in the solar spectrum and the inefficient separation of photoinduced electron-hole pairs hamper the practical application of TiO_(2) materials.To overcome the aforementioned serious drawbacks of TiO_(2),numerous strategies,such as doping with foreign atoms,particularly nitrogen(N),have been improved in the past few decades.This review aims to provide a comprehensive update and description of the recent developments of N-doped TiO_(2) materials for visible lightresponsive photocatalysis,such as(1)the preparation of N-doped/co-doped TiO_(2) photocatalysts and(2)mechanistic studies on the reasons for visible light response.Furthermore,the most recent and significant advances in the field of solar energy applications of modified N-doped TiO_(2) are summarized.The analysis indicated the critical need for further development of these types of materials for the solar-to-energy conversion,particularly for water splitting purposes.

Light-responsive Self-Immolative L-glutamic Acid-based Polyester Nanoparticles for Controlled Drug Release via Passerini Three-Component Polymerization

L-glutamic acid(LA)is a bio-based,non-toxic,environmentally friendly material derived from biomass.The present study reports the application of Passerini three-component polymerization(P-3CP)for the straightforward preparation of LA-based light-responsive polyesters(PLTDs)under mild conditions.PLTDs with molar masses up to 8500 g/mol and high yields exceeding 90%are obtained.The chemical structures and light-responsive self-immolative behavior of PLTDs are comprehensively characterized by employing ultraviolet-visible(UV-Vis)spectroscopy,size exclusion chromatography(SEC),nuclear magnetic resonance(NMR)spectroscopy,and liquid chromatography mass spectrometry(LC-MS).Meanwhile,monodisperse PLTD-based doxorubicin-loaded nanoparticles(PLTD-DOX-NP)(size=193 nm,PDI=0.018)are formulated by nanoprecipitation method.Upon light-induced depolymerization,the PLTD-DOX-NP undergoes rapid decomposition,resulting in a burst release of 80%cargo within 13 s.Furthermore,according to biological toxicity tests,the PLTD-NP possesses adequate biosafety,both before and after irradiation.Overall,the incorporation of P-3CP with biorenewable LA-based monomer adheres to the principles of green chemistry,significantly simplifying the synthetic pathway of light-responsive polymers.

Light-responsive nanomedicine for cancer immunotherapy

Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control,light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.

Light-responsive organic artificial enzymes:Material designs and bio-applications

As significant biocatalysts,natural enzymes have exhibited a vast range of applications in biocatalytic reactions.However,the“always-on”natural enzyme activity is not beneficial for the regulation of catalytic processes,which limits their bio-applications.Recently,it has been extensively reported that various organic artificial enzymes exhibit prominent absorption and controlled activity under illumination,which not only creates a series of light-responsive catalytic platforms but also plays a key role in biosensing and biomedical research.To provide novel ideas for the design of artificial enzymes,we conduct this review to highlight the recent progress of light-responsive organic artificial enzymes(LOA-Enz).The specific photoresponse mechanism and various bio-applications of LOA-Enz are also presented in detail.Furthermore,the remaining challenges and future perspectives in this field are discussed.

HY5 regulates light-responsive transcription of microRNA163 to promote primary root elongation in Arabidopsis seedlings

MicroRNAs(miRNAs)play key roles in the post-transcriptional regulation of gene expression in plants.Many miRNAs are responsive to environmental signals.Light is the first environmental signal perceived by plants after emergence from the soil.However,less is known about the roles and regulatory mechanism of miRNAs in response to light signal.Here,using small RNA sequencing,we determined that miR163 is significantly rapidly induced by light signaling in Arabidopsis thaliana seedlings.The light-inducible response of miR163 functions genetically downstream of LONG HYPOCOTYL 5(HY5),a central positive regulator of photomorphogenesis.HY5 directly binds to the two G/C-hybrid elements in the miR163 promoter with unequal affinity;one of these elements,which is located next to the transcription start site,plays a major role in light-induced expression of miR163.Overexpression of miR163 rescued the defective primary root elongation of hy5 seedlings without affecting lateral root growth,whereas overexpressing of miR163 target PXMT1 inhibited primary root elongation.These findings provide insight into understanding the post-transcriptional regulation of root photomorphogenesis mediated by the HY5-miR163-PXMT1 network.

Light-responsive charge-reversal nanovector for high-efficiency in vivo CRISPR/Cas9 gene editing with controllable location and time

Controllably and efficaciously localized CRISPR/Cas9 plasmids transfection plays an essential role in genetic editing associated with various key human diseases.We employed near-infrared(NIR)light-responsive CRISPR/Cas9 plasmids delivery via a charge-reversal nanovector to achieve highly efficient and site-specific gene editing.The nanovector with abundant positive charges was fabricated on the basis of an ultraviolet-sensitive conjugated polyelectrolyte coated on an upconversion nanomaterial(UCNP-UVP-P),which can convert into negative charges upon 980 nm light irradiation.Using the as-prepared nanovector,we demonstrated the plasmids could be efficiency transfected into tumor cells(~63%±4%)in a time-contolled manner,and that functional CRISPR/Cas9 proteins could be successfully expressed in a selected NIR-irradiated region.Particularly,this strategy was successfully applied to the delivery of CRISPR/Cas9 gene to tumor cells in vivo,inducing high efficiency editing of the target gene PLK-1 under photolrradiation.Therefore,this precisely controlled gene regulation strategy has the potential to serve as a new paradigm for gene engineering in complex biological systems.

Light-responsive nanocomposites combining graphene oxide with POSS based on host-guest chemistry

Based on the reversible host-guest inclusion/exclusion of cyclodextrin-functionalized graphene oxide(GO-CD) and azobenzene-terminated polyhedral oligomeric silsesquioxane(Azo-POSS), a novel kind of light-responsive nanocomposites GO-POSS was developed under mild condition. ~1H NMR, ET-IR,TG, TEM and UV-vis spectroscopy were conducted to characterize the chemical composition and photoresponsive performance of obtained GO-POSS nanocomposites. The results demonstrated that nanocagestructured POSS and nanosheet GO components in GO-POSS exhibited pronounced supra molecular assembly/disassembly behavior upon UV/vis irradiation. Moreover, GO-POSS nanocomposites showed good water dispersity and had remarkable impact on oxygen permeability of conventional PVA-coated films under varied light irradiation conditions, which would be valuable for developing smart gas barrier materials in packaging.

Smart light-responsive hierarchical metal organic frameworks constructed mixed matrix membranes for efficient gas separation

One type of new light-responsive hierarchical metal organic framework(MOF) has been successfully prepared using Co(NO_(3))_(3)·6H_(2)O as the metal salt and 4,4’-azobenzenedicarboxylic acid as the ligand by microwave method for the first time. It is found that MOF [Co(Az DC)] exhibits a light-responsive characteristic to SO_(2)adsorption due to the presence of azo group from the ligand. The light-responsive hierarchical MOFs are incorporated into Matrimid■ 5218(PI) matrix to prepare mixed matrix membranes(MMMs) for gas separation application. The morphology, crystallinity, chain mobility and thermal stability of MMMs are explored. Results show that Co(Az DC) may elevate both the CO_(2)(SO_(2)) permeability and CO_(2)(SO_(2))/N_(2)selectivity of the MMMs. In particular,the Co(Az DC) doped MMMs exhibit the significantly improved CO_(2)(SO_(2))/N_(2)selectivity from 33(123) for PI control membrane to 78(420) for MMMs, overcoming the 2008 Robeson upper bound for CO_(2)/N_(2)system. Sizesieving effect of Co(Az DC) with pore size 0.35 nm enhances the selectivity, while the –N=N– group from Co(Az DC) shows affinity to CO_(2)molecular rather than N_(2), also elevating selectivity of MMMs. In brief, enhanced selectivity of high-performance membrane is attributed to incorporation of Co(Az DC) particles, which displays synergistic effects both in size-sieving and CO_(2)-philic interaction for CO_(2)/N_(2)separation. Smart highly selective interface is constructed in MMMs by switching the configuration of MOFs from cis to trans. The SO_(2)permeability and SO_(2)/N_(2)selectivity of MMMs are investigated under both visible light and ultraviolet light states, and the SO_(2)/N_(2)separation performance under visible light is notably improved in comparison with that under ultraviolet light state.

Light-responsive color switching of self-doped TiO_(2-x)/WO_(3)·0.33H_(2)O hetero-nanoparticles for highly efficient rewritable paper

Smart materials that reversibly change color upon light illumination are widely explored for diverse appealing applications.However,light-responsive color switching materials are mainly limited to organic molecules.The synthesis of inorganic counterparts has remained a significant challenge because of their slow light response and poor reversibility.Here,we report a seeded growth strategy for the synthesis of TiO_(2-x)/WO_(3)·0.33H_(2)Ohetero-nanoparticles(HNPs)with networked wire-like structure of〜10 nm in diameters that enable the highly reversible light-responsive color switching properties.For the TiO_(2-x)/WO_(3)·0.33H_(2)OHNPs,T P species self-doped in TiO_(2-x)nanoparticles(NPs)act as efficient sacrificial electron donors(SEDs)and Ti-O-W linkages formed between TiO2-x and WO30.33H2O NPs ensure the nanoscale interfacial contact,endowing the HNPs enhanced photoreductive activity and efficient interfacial charge transfer upon ultraviolet(UV)illumination to achieve highly efficient color switching.The TiO_(2-x)/WO_(3)·0.33H_(2)OHNPs exhibits rapid light response(<15 s)and long reversible color switching cycles(>180 times).We further demonstrate the applications of TiO_(2-x)/WO_(3)·0.33H_(2)O HNPs in ink-free,light-printable rewritable paper that can be written on freehand or printed on through a photomask using UV light.This work opens an avenue for designing inorganic light-responsive color switching nanomaterials and their smart applications.

Modified non-rectangular hyperbola equation with plant height for photosynthetic light-response curves of Potentilla anserina and Elymus nutans at various growth phases in the Heihe River Basin, Northwest China

The non-rectangular hyperbola(NRH)equation is the most popular method that plots the photosynthetic light-response(PLR)curve and helps to identify plant photosynthetic capability.However,the PLR curve can't be plotted well by the NRH equation at different plant growth phases due to the variations of plant development.Recently,plant physiological parameters have been considered into the NRH equation to establish the modified NRH equation,but plant height(H),an important parameter in plant growth phases,is not taken into account.In this study,H was incorporated into the NRH equation to establish the modified NRH equation,which could be used to estimate photosynthetic capability of herbage at different growth phases.To explore photosynthetic capability of herbage,we selected the dominant herbage species Potentilla anserina L.and Elymus nutans Griseb.in the Heihe River Basin,Northwest China as the research materials.Totally,twenty-four PLR curves and H at different growth phases were measured during the growing season in 2016.Results showed that the maximum net photosynthetic rate and the initial slope of PLR curve linearly increased with H.The modified NRH equation,which is established by introducing H and an H-based adjustment factor into the NRH equation,described better the PLR curves of P.anserina and E.nutans than the original ones.The results may provide an effective method to estimate the net primary productivity of grasslands in the study area.

Preparation and evaluation of controllable drug delivery system:A light responsive nanosphere based on β-cyclodextrin/mesoporous silica

A novel light responsive nanosphere was constructed,and it was used as a drug carrier to investigate the loading and release properties of the Quercetin(QU).In this paper,mesoporous silica nanoparticles(MSN)were used as a substrate,and 3-aminopropyl triethyoxysilane was used as a surface modification agent to introduce—NH_(2),and the azobenzene-4,4’-dicarboxylic acid(AZO)was used as light responsive agent to introduce the group of—N=N—,and thenβ-cyclodextrin(β-CD)was combined with AZO through host-guest interaction to construct light responsive nanoparticles(MSN@β-CD).The structure and properties of the carrier were analyzed by FTIR,BET,XPS,TGA,XRD,SEM and TEM.In vitro drug release studies showed the release rate of QU@MSN@β-CD(dark)was 12.19%within 72 h,but the release rate of QU@MSN@β-CD(light 10 min)was 26.09%,exhibiting a light-responsive property.The CCK8 tests demonstrated that MSN@β-CD could significantly decrease the toxicity of QU.Therefore,the controllable light-responsive drug delivery system has great application prospects.

Promoting oral mucosal wound healing using a DCS-RuB_(2)A_(2) hydrogel based on a photoreactive antibacterial and sustained release of BMSCs

The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals.Following the development of oral mucosal lesions,the oral microenvironment changes,immunity declines,and continuous bacterial stimulation causes wound infection.Traditional antibacterial drugs are ineffective for oral mucosal lesions.To overcome this problem,a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity,which is different from that on the body surface since it mostly remains under dark conditions.In the absence of light,the hydrogel seals the wound to form a barrier,exerts a natural bacteriostatic effect,and prevents invasion by foreign bacteria.Simultaneously,mesenchymal stem cells are presented,and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects,which result in rapid repair of the damaged site.Under light conditions,after photo-induced shedding of the hydrogel,RuB_(2)A exerts an antibacterial effect accompanied by degradation of the hydrogel.Results in a rat oral mucosal repair model demonstrate that DCS-RuB_(2)A_(2)-BMSCs could rapidly repair the oral mucosa within 4 days.Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways.Taken together,our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.

iRGD-reinforced, photo-transformable nanoclusters toward cooperative enhancement of intratumoral penetration and antitumor efficacy

Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-responsive nanoclusters (NCs) capable of size shrinkage and charge conversion were developed and co-administered with iRGD to synergistically improve the intratumoral penetration and the anticancer efficacy. The NCs were constructed using the singlet oxygen-sensitive (SOS) polyethylene glycolpolyurethane-polyethylene glycol (PEG-(1O2)PU-PEG) triblock copolymer to encapsulate the doxorubicin (DOX)-loaded, chlorin e6 (Ce6)-conjugated polyamindoamine (PAMAM) dendrimer (DCD) via the double-emulsion method. Co-administration of iRGD notably increased the permeability of NCs within tumor vasculature and tumor tissues. In addition, upon far-red light irradiation (660 nm) of tumors at low optical density (10 mW/cm2), the generated 1O2 could disintegrate the NCs and release the DCD with positive surface charge and ultra-small size (~ 5 nm), which synergized with iRGD to enable deep intratumoral penetration. Consequently, the local 1O2 at lethal concentrations along with the released DOX efficiently and cooperatively eradicated tumor cells. This study provides a convenient approach to spatiotemporally promote the intratumoral penetration of nanomedicine and mediate programmed anticancer therapy.

Light-induced dynamic RGD pattern for sequential modulation of macrophage phenotypes

Due to the critical roles of macrophage in immune response and tissue repair,harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions.Although there have developed many advanced platforms with dynamic features for cell manipulation,few studies have designed a dynamic chemical pattern to sequentially polarize macrophage phenotypes and meet the immune requirements at various tissue repair stages.Here,we propose a novel strategy for spatiotemporal manipulation of macrophage phenotypes by a UV-induced dynamic Arg-Gly-Asp(RGD)pattern.By employing a photo-patterning technique and the specific interaction between cyclodextrin(CD)and azobenzene-RGD(Azo-RGD),we prepared a polyethylene glycol-dithiol/polyethylene glycol-norbornene(PEG-SH/PEG-Nor)hydrogel with dynamic RGD-patterned surface.After irradiation with 365-nm UV light,the homogeneous RGD surface was transformed to the RGD-patterned surface which induced morphological transformation of macrophages from round to elongated and subsequent phenotypic transition from pro-inflammation to anti-inflammation.The mechanism of phenotypic polarization induced by RGD pattern was proved to be related to Rho-associated protein kinase 2(ROCK2).Sequential modulation of macrophage phenotypes by the dynamic RGD-patterned surface provides a remote and non-invasive strategy to manipulate immune reactions and achieve optimized healing outcomes.

Essential oils as solvents and core materials for the preparation of photo-responsive polymer nanocapsules

Light-triggered release of active ingredients from polymeric nanosized capsules can be employed in a wide range of applications, such as biomedicine, active packaging, and cosmetics. However, the preparation of core-shell polymeric nanocarriers typically involves the use of toxic organic solvents. To improve the sustainability and safety of nanocapsule applications, we demonstrate that natural essential oils can be used both as solvent and active material in light-responsive nanocapsules synthesized via miniemulsion polycondensation. The documented antimicrobial, anti-inflammatory, and antioxidant activity of essential oils enables the design of multipurpose light-responsive delivery platforms. The photo-responsive behavior of the capsules, achieved by means of photochromic azobenzene segments embedded in the capsule shell, is triggered by UV light irradiation （λmax= 360 nm）. Light-induced release kinetics of the essential oils and a fluorescent probe molecule, coumarin-6, is evaluated via UV-vis spectroscopy and spectrofluorimetry, respectively, demonstrating the efficiency and reliability of the release mechanism. Biological tests prove that the capsules are non-cytotoxic and readily internalized by cells, indicating the suitability of these smart nanocarriers for biological applications.