Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy

Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“precise strike”of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid(HA)and hypoxia-dependent factor carbonic anhydrase IX(CA IX)-inhibitor acetazolamide(AZ).The core of nanobullets is the special zinc(II)phthalocyanine aggregates(ZPA)which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy(PTT),along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy(TDT).The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional(reactive oxygen species(ROS)-mediated)cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.

Bioinspired nanotransducers for neuromodulation

The field of neuromodulation has experienced significant advancements in the past decade,owing to breakthroughs in disciplines such as materials science,genetics,bioengineering,photonics,and beyond.The convergence of these fields has resulted in the development of nanotransducers,devices that harness the synergies of these diverse disciplines.These nanotransducers,essential for neuromodulation,often draw inspiration from energy conversion processes found in nature for their unique modalities.In this review,we will delve into the latest advancements in wireless neuromodulation facilitated by optical,magnetic,and mechanical nanotransducers.We will examine their working principles,properties,advantages,and limitations in comparison to current methods for deep brain neuromodulation,highlighting the impact of natural systems on their design and functionality.Additionally,we will underscore potential future directions,emphasizing how continued progress in materials science,neuroscience,and bioengineering might expand the horizons of what is achievable with nanotransducer-enabled neuromodulation.

Biological imaging without autofluorescence in the second near-infrared region

Fluorescence imaging is capable of acquiring anatomical and functional infor- mation with high spatial and temporal resolution. This imaging technique has been indispensable in biological research and disease detection/diagnosis. Imaging in the visible and to a lesser degree, in the near-infrared （NIR） regions below 900 nm, suffers from autofluorescence arising from endogenous fluorescent molecules in biological tissues. This autofluorescence interferes with fluorescent molecules of interest, causing a high background and low detection sensitivity. Here, we report that fluorescence imaging in the 1,500-1,700-nm region （termed ＂NIR-IIb＂） under 808-nm excitation results in nearly zero tissue autofluorescence, allowing for background-free imaging of fluorescent species in otherwise notoriously autofluorescent biological tissues, including liver. Imaging of the intrinsic fluorescence of individual fluorophores, such as a single carbon nanotube, can be readily achieved with high sensitivity and without autofluorescence background in mouse liver within the 1,500-1,700-nm wavelength region.

Controlled afterglow luminescent particles for photochemical tissue bonding

Upconversion materials(UCMs)have been developed to convert tissue-penetrating near-infrared(NIR)light into visible light.However,the low energy conversion effciency of UCMs has limited their further biophotonic applications.Here,we developed controlled afterglow luminescent particles(ALPs)of ZnS:Ag,Co with strong and persistent green luminescence for photochemical tissue bonding(PTB).The co-doping of Ag^(+) and Co^(2+) ions into ZnS:Ag,Co particles with the proper vacancy formation of host ions resulted in high luminescence intensity and long-term afterglow.In addition,the ALPs of ZnS:Ag,Co could be recharged rapidly under short ultraviolet(UV)irradiation,which effectively activated rose bengal(RB)in hyaluronate-RB(HA-RB)conjugates for the crosslinking of dissected collagen layers without additional light irradiation.The remarkable PTB of ZnS:Ag,Co particles with HA-RB conjugates was confirmed by in vitro collagen fibrillogenesis assay,in vivo animal wound closure rate analysis,and in vivo tensile strength evaluation of incised skin tissues.Taken together,we could confirm the feasibility of controlled ALPs for various biophotonic applications.