Pulsed Laser Excited Photoacoustic Effect for Disease Diagnosis and Therapy

Pulsed laser can excite light absorber to generate photoacoustic (PA) effect, that is, when the absorber is irradiated with pulsed laser, the absorbed light energy is converted into local heat to cause rapid thermoelastic expansion and generate acoustic wave. The generated PA signal has been widely employed for the diagnosis of many diseases with superb contrast, high penetrability and sensitivity. In addition, with the increase of pulsed laser energy, the resulting PA shockwave and cavitation can promote efficient drug release at lesion sites to potentiate the resulting therapeutic efficacy. Furthermore, the PA shockwave/cavitation can mechanically inhibit disease and produce reactive species. In this Concept article, the principle and research status of pulsed laser excited disease theranostics are briefly summarized, extra suggestions are proposed to inspire extensive PA probes and photodynamic materials as well as novel methodologies.     

An Alkynyl-Dangling Ru(II) Polypyridine Complex for Targeted Antimicrobial Photodynamic Therapy

To realize clinical application of antibacterial photodynamic therapy (aPDT), one of the most arduous challenges is how to render aPDT agents high selectivity against bacterial pathogens. In light of the fact that amino group-containing lipids are rich on the outer surfaces of Gram-positive bacteria, we herein constructed an alkynyl-dangling ruthenium(II) polypyridine complex (Ru2) to preferentially label Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) over mammalian cells via the amino-yne bio-orthogonal click reaction. Thanks to the strong singlet oxygen generation ability, Ru2 could photo-inactivate S. aureus and MRSA effectively and specifically. Phosphatidylethanolamine (PE) molecules also exist in mammalian cells but are not accessible for Ru2, leading to its poor binding/uptake and negligible cytotoxicity in the dark and upon irradiation towards mammalian cells as well as low hemolysis, all favorable for aPDT application.     

Transition Metal Dichalcogenides for Sensing and Oncotherapy: Status,Challenges, and Perspective

Transition metal dichalcogenides (TMDCs) are increasingly being used for chemical sensing, biosensing, and tumor therapy on account of their diversity, biocompatibility, multifunctionality, adjustable bandgap, and excellent photoelectric characteristics. This review mainly discusses the effect of the elemental composition and structure of TMDCs on the performance of electrochemical, biofluorescence, and colorimetric biosensors. The applications of TMDCs in tumor therapies are reviewed here. Furthermore, the current challenges and future directions for developing TMDC-based theranostics are summarized.     

A low-cost invasive microwave ablation antenna with a directional heating pattern

Microwave ablation (MWA) is a cancer treatment method. The tumor tissue absorbs electromagnetic energy, which heats and kills it. A microwave ablation antenna plays a critical role in this process. Its radiation field must completely cover the tumor but not the healthy tissue. At present, the radiation pattern of most invasive ablation antennas is spherical. However, in the clinic, the shape of some tumors may be asymmetrical or the antenna cannot be inserted into the center of the tumor for some other reason. In order to solve these problems, a directional heating antenna for microwave ablation is proposed in this paper. The proposed antenna, operating at 2.45 GHz, consists of a monopole and a reflector. The feed is given by a substrate integrated coaxial line (SICL) and coplanar waveguide (CPW). The omnidirectional radiation field of the monopole is reflected by a reflector that is extended from the outer conductors of the SICL to form a directional radiation field. The impedance matching network is designed on SICL to match the antenna to 50 Ω . The antenna is fabricated using a mature printed circuit board (PCB). The reflection coefficient of the antenna in porcine liver tissue measured by a vector network analyzer shows good agreement with the simulations. Then, an ablation experiment in porcine liver is conducted with power of 10 W for 10 min, and the experimental results confirm the validity of the design.     

PEGylated Poly-HDACi: A Designer Polyprodrug from Optimized Drug Units**

We designed, synthesized, and characterized a tri-block copolymer. Its hydrophobic part, a chain of histone deacetylase inhibitor (HDACi) prodrug, was symmetrically flanked by two identical PEG blocks, whereas the built-in HDACi was a linear molecule, terminated with a thiol at one end, and a hydroxyl group at the other. Such a feature facilitated end-to-end linkage of prodrugs through alternatively aligned disulfides and carbonates. The disulfides served dual roles: redox sensors of smart nanomedicine, and warheads of masked HDACi drugs. This approach, carefully designed to benefit both control-release and efficacy, is conceptually novel for optimizing drug units in nanomedicine. Micelles from this designer polyprodrug released only PEG, CO₂ and HDACi, and synergized with DOX against HCT116 cells, demonstrating its widespread potential in combination therapy. Our work highlights, for the first time, the unique advantage of thiol-based drug molecules in nanomedicine design.     

Recent advances in platelet engineering for anti-cancer therapies

Platelets contribute a major role in hemostasis by clumping and coagulation at the site of blood vessel injuries. In light of recent findings of a close relationship between platelets and immunological response, as well as interactions between platelets and cancer cells, novel engineering strategies have emerged for the integration of platelets or platelet membrane (PM) with anti-cancer therapeutics. In this review, we discuss several recent innovations that use platelets or their membranes to circumvent host immune responses and target tumor cells with high specificity to deliver a range of pharmacological, photothermal, or immunologic agents for eradication of recalcitrant tumor cells. More specifically, we compare the relative advantages of using whole platelets versus single or hybrid PM to coat nanoparticle cargoes. These cargoes range from well-established anti-tumor apoptosis-inducing agents, to relatively new photothermal agents that can induce a feedback cascade in which they induce vascular damage to the tumor which recruits more platelet- or membrane-encapsulated agents to induce further damage. We also discuss the use of engineered platelets to produce programmed cell death-inducing platelet derived microparticles. This review provides an overview and future directions for this promising platelet-based biomimetic approach to anti-cancer therapy.     

A Traceable,Sequential Multistage-Targeting Nanoparticles Combining Chemo/Chemodynamic Therapy for Enhancing Antitumor Efficacy

Although chemodynamic therapy (CDT) can effectively inhibit tumor growth and metastasis, it is challenging to eliminate tumors. Generally, CDT needs to combine with extra therapeutic modes for enhancing antitumor efficacy. Here, novel nanoparticles (BDTLAG NPs) are constructed via self-assembly of cancer cell targeting prodrug (Bio-PEG_2K-S-S-CPT), organic CDT agents (TPP-PEG_2K-LND, TPP-PEG_2K-TOS), pH-responsive prodrug (PEG_2K-NH-N-DOX), T1-enhanced magnetic resonance imaging contrast agents (Gd-DTPA-N16-16), and anti-angiogenic drug combrestatinA4 (CA4), realizing chemo(CT)-chemodynamic combination therapy. The mechanism of BDTLAG NPs for enhancing antitumor efficacy involves: (i) BDTLAG NPs is accumulated in the tumor tissue by passive targeting; (ii) CA4 is released and specifically destroys angiogenesis, and the remaining BDTLG NPs enter the tumor cell via active targeting; (iii) the acid/glutathione (GSH)-responsive prodrug release and GSH depletion; (iv) TPP-PEG_2K-LND and TPP-PEG_2K-TOS are accumulated in the tumor cell mitochondria due to mitochondria-targeting, and is accompanied by endogenous reactive oxygen species bursts. This current strategy of single NPs that integrates spatiotemporally CT, CDT, GSH depletion, and MR imaging functions reflects the “all in one” concept, which provides a new opportunity for enhancing antitumor efficacy.     

Nanoagent-Promoted Mild-Temperature Photothermal Therapy for Cancer Treatment

Photothermal therapy (PTT), which utilizes near-infrared light-absorbing agents to ablate tumor, has emerged as a highly promising anticancer strategy and received intensive clinical trials in recent years. Mild-temperature PTT, which circumvents the limitations of conventional PTT (e.g., thermoresistance and adverse effects), is emerging and shows great potential in the forthcoming clinical applications. However, mild-temperature PTT without adjuvant therapy is not able to completely eradicate tumors because its therapeutic efficacy is dramatically impaired by its inferior heat intensity. As a result, strategies capable of enhancing the anticancer efficacy of mild-temperature PTT are urgently necessitated, which mainly rely on on-demand fabrication of functionalized nanoagents. In this review, the strategies of nanoagent-promoted mild-temperature PTT are highlighted. Furthermore, challenges and opportunities in this field are rationally proposed, and hopefully people can be encouraged by this promising anticancer therapy.     

Dipyrrinato-Iridium(III) Complexes for Application in Photodynamic Therapy and Antimicrobial Photodynamic Inactivation

The generation of bio-targetable photosensitizers is of utmost importance to the emerging field of photodynamic therapy and antimicrobial (photo-)therapy. A synthetic strategy is presented in which chelating dipyrrin moieties are used to enhance the known photoactivity of iridium(III) metal complexes. Formed complexes can thus be functionalized in a facile manner with a range of targeting groups at their chemically active reaction sites. Dipyrrins with N- and O-substituents afforded (dipy)iridium(III) complexes via complexation with the respective Cp*-iridium(III) and ppy-iridium(III) precursors (dipy=dipyrrinato, Cp*=pentamethyl-η⁵-cyclopentadienyl, ppy=2-phenylpyridyl). Similarly, electron-deficient [Ir^III(dipy)(ppy)₂] complexes could be used for post-functionalization, forming alkenyl, alkynyl and glyco-appended iridium(III) complexes. The phototoxic activity of these complexes has been assessed in cellular and bacterial assays with and without light; the [Ir^III(Cl)(Cp*)(dipy)] complexes and the glyco-substituted iridium(III) complexes showing particular promise as photomedicine candidates. Representative crystal structures of the complexes are also presented.     

Dual Enzyme Mimics Based on Metal–Ligand Cross-Linking Strategy for Accelerating Ascorbate Oxidation and Enhancing Tumor Therapy

The development of high-efficiency nanozymes is of great significance in the field of nanozymology, because this is one of the prerequisites for the sophisticated performance of nanozymes. Herein, the developed metal–ligand cross-linking strategy engineers porous carbon nanorod supported ultra-small iron carbide nanoparticles that possess excellent oxidase-like and peroxidase-like enzyme activities. The fabricated nanozyme can efficiently accelerate the oxidation of ascorbate (AA) to enhance cancer cells ablation efficacy. Due to the nanozyme having great surface atoms utilization ratio and large specific surface area, the AA can be rapidly and completely autoxidized within 20 min. Mechanism research demonstrates that the nanozyme's first activation of O₂ to generate superoxide free radicals (O₂^•−) via the oxidase-like pathway, then the O₂^•− directly oxidizes AA and produces hydrogen peroxide (H₂O₂). Simultaneously, the H₂O₂ transforms into the toxic hydroxyl radical through the peroxidase-like pathway and induces tumor cell death. Further in vitro and in vivo assays show the significant enhancement of the anti-tumor efficacy through AA oxidation which is catalyzed by the developed nanozyme. It is expected that this work will benefit not only the development of other efficient nanozymes, but also future advances in the field of AA oxidation induced tumor therapy.