NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

Light focusing in linear arranged symmetric nanoparticle trimer on metal film system

Benefiting from the induced image charge on film surface,the nanoparticle aggregating on metal exhibits interesting optical properties.In this work,a linear metal nanoparticle trimer on metal film system has been investigated to explore the novel optical phenomenon.Both the electric field and surface charge distributions demonstrate the light is focused on film greatly by the nanoparticles at two sides,which could be strongly modulated by the wavelength of incident light.And the influence of nanoparticle in middle on this light focusing ability has also been studied here,which is explained by the plasmon hybridization theory.Our finding about light focusing in nanoparticle aggregating on metal film not only enlarges the novel phenomenon of surface plasmon but also has great application prospect in the field of surface-enhanced spectra,surface catalysis,solar cells,water splitting,etc.

Controllable and switchable chiral near-fields in symmetric graphene metasurfaces

A strong chiral near-field plays significant roles in the detection,separation and sensing of chiral molecules.In this paper,a simple and symmetric metasurface is proposed to generate strong chiral near-fields with both circularly polarized light and linearly polarized light illuminations in the mid-infrared region.Owing to the near-field interaction between plasmonic resonant modes of two nanosheets excited by circularly polarized light,there is a strong single-handed chiral near-field in the gap between the two graphene nanosheets and the maximum enhancement of the optical chirality could reach two orders of magnitude.As expected,the intensity and the response wavelength of the chiral near-fields could be controlled by the Fermi level and geometrical parameters of the graphene nanosheets,as well as the permittivity of the substrate.Meanwhile,based on the interaction between the incident field and scattered field,the one-handed chiral nearfield in the gap also could be generated by the linearly polarized light excitation.For the two cases,the handedness of the chiral near-field could be switched by the polarized direction of the incident light.These results have potential opportunities for applications in molecular detection and sensing.

Mitochondria-targeted Janus mesoporous nanoplatform for tumor photodynamic therapy

Photodynamic therapy(PDT)is an effective treatment method for tumors.But the specifically accumulated of photosensitizer was very difficult in the tumor site,which greatly limited the efficacy of PDT.Here,mitochondria-targeted Janus mesoporous nanoplatform(JPMO-Pt-CTPP-ZnPc)for PDT was prepared,the nanoplatform has uniform size(275 nm)and good dispersion and biocompatibility.The confocal laser scanning microscopy(CLSM)revealed the signal of ZnPc of JPMO-Pt-CTPP-ZnPc were higher than JPMO-Pt-ZnPc in tumor cells,and flow cytometry results showed the cell uptake efficiency of JPMO-Pt-CTPP-ZnPc was 2.5-fold higher than that of JPMO-Pt-ZnPc.This revealed the modification of CTPP significantly improves the targeting ability of the nanoplatform.In vitro anti-tumor experiment showed the JPMO-Pt-CTPP-ZnPc significantly inhibited the growth of tumor cells upon the irradiation of low-power laser,and the survival rate of cells incubated with 60μg/mL JPMO-Pt-CTPP-ZnPc was only 3%.Simultaneously,compared with JPMO-Pt-ZnPc(not modified with mitochondria targeting molecules CTPP),the PDT efficacy of JPMO-Pt-CTPP-ZnPc was significantly better,as it has targeted mitochondria in cells.

Computed tomography and photoacoustic imaging guided photodynamic therapy against breast cancer based on mesoporous platinum with insitu oxygen generation ability

Photodynamic therapy(PDT)has been widely used in cancer treatment.However,hypoxia in most solid tumors seriously restricts the efficacy of PDT.To improve the hypoxic microenvironment,we designed a novel mesoporous platinum(mPt)nanoplatform to catalyze hydrogen peroxide(H2 O2)within the tumor cells in situ without an extra enzyme.During the fabrication,the carboxy terminus of the photosensitizer chlorin e6(Ce6)was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol(SH-PEG-NH2)by a condensation reaction,and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2.Material,cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2 O2 to produce oxygen(O2)and that Ce6 transformed O2 to generate reactive oxygen species(ROS)upon laser irradiation.The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation.Due to the high atomic number and good near-infrared absorption for Pt,this Pt@PEG-Ce6 nanoplatform showed computed tomography(CT)and photoacoustic(PA)dual-mode imaging ability,thus providing an important tool for monitoring the tumor hypoxic microenvironment.Moreover,the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-la(HIF-1α)and programmed death-1(PD-1)in tumors,discussing the relationship between hypoxia,PD-1,and PDT for the first time.

Disruption of Zfh3 abolishes mulberry-specific monophagy in silkworm larvae

Feeding behavior is critical for insect survival and fitness.Most researchers have explored the molecular basis of feeding behaviors by identifying and elucidating the function of olfactory receptors(ORs)and gustatory receptors(GRs).Other types of genes,such as transcription factors,have rarely been investigated,and little is known about their potential roles.The silkworm(Bombyx mori)is a well-studied monophagic insect which primarily feeds on mulberry leaves,but the genetic basis of its monophagy is still not un-derstood.In this report,we focused on a transcription factor encoded by the Zfh3 gene,which is highly expressed in the silkworm central and peripheral nervous systems,in-cluding brain,antenna,and maxilla.To investigate its function,Zfh3 was abrogated using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated protein 9(Cas9)mutagenesis.Since Zfh3 knockout homozygotes are not viable,we stud-ied feeding behavior in heterozygotes,and found that disruption of Zfh3 affects both gus-tation and olfaction.Mutant larvae lose preference for mulberry leaves,acquire the ability to consume an expanded range of diets,and exhibit improved adaptation to the Mo artifi-cial diet,which contains no mulberry leaves.These results provide the first demonstration that a transcription factor modulates feeding behaviors in an insect.