Hypoxia, a quite universal feature in most solid tumors, has been considered as the "Achilles' heel" of traditional photodynamic therapy (PDT) and substantially impairs the overall therapeutic efficacy. Herein, we develop a near-infrared (NIR) light-triggered molecular superoxide radical (O 2 −• ) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O 2 −• action mechanism underlying the antihypoxia effects, and confirm its application for in vivo targeted hypoxic solid tumor ablation. Photomediated radical generation mechanism study shows that, even under severe hypoxic environment (2% O 2 ), ENBS-B can generate considerable O 2 −• through type I photoreactions, and partial O 2 −• is transformed to high toxic OH• through SODmediated cascade reactions. These radicals synergistically damage the intracellular lysosomes, which subsequently trigger cancer cell apoptosis, presenting a robust hypoxic PDT potency. In vitro coculture model shows that, benefiting from biotin ligand, ENBS-B achieves 87-fold higher cellular uptake in cancer cells than normal cells, offering opportunities for personalized medicine. Following intravenous administration, ENBS-B is able to specifically target to neoplastic tissues and completely suppresses the tumor growth at a low light-dose irradiation. As such, we postulated this work will extend the options of excellent agents for clinical cancer therapy.

Traditional photothermal therapy requires high‐intensity laser excitation for cancer treatments due to the low photothermal conversion efficiency (PCE) of photothermal agents (PTAs). PTAs with ultra‐high PCEs can decrease the required excited light intensity, which allows safe and efficient therapy in deep tissues. In this work, a PTA is synthesized with high PCE of 88.3% based on a BODIPY scaffold, by introducing a CF3 “barrier‐free” rotor on the meso‐position (tfm‐BDP). In both the ground and excited state, the CF3 moiety in tfm‐BDP has no energy barrier to rotation, allowing it to efficiently dissipate absorbed (NIR) photons as heat. Importantly, the barrier‐free rotation of CF3 can be maintained after encapsulating tfm‐BDP into polymeric nanoparticles (NPs). Thus, laser irradiation with safe intensity (0.3 W cm−2, 808 nm) can lead to complete tumor ablation in tumor‐bearing mice after intravenous injection of tfm‐BDP NPs. This strategy of “barrier‐free rotation” provides a new platform for future design of PTT agents for clinical cancer treatment.

Strong oxygen dependence, poor tumor targeting, and limited treatment depth have been considered as the “Achilles’ heels” facing the clinical usage of photodynamic therapy (PDT). Different from common approaches, here, we propose an innovative tactic by using photon-initiated dyad cationic superoxide radical (O2 –•) generator (ENBOS) featuring “0 + 1 > 1” amplification effect to simultaneously overcome these drawbacks. In particular, by taking advantage of the Förster resonance energy transfer theory, the energy donor successfully endows ENBOS with significantly enhanced NIR absorbance and photon utility, which in turn lead to ENBOS more easily activated and generating more O2 –• in deep tissues, that thus dramatically intensifies the type I PDT against hypoxic deep tumors. Moreover, benefiting from the dyad cationic feature, ENBOS achieves superior “structure-inherent targeting” abilities with the signal-to-background ratio as high as 25.2 at 48 h post intravenous injection, offering opportunities for accurate imaging-guided tumor treatment. Meanwhile, the intratumoral accumulation and retention performance are also markedly improved (>120 h). On the basis of these unique merits, ENBOS selectively inhibits the deep-seated hypoxic tumor proliferation at a low light-dose irradiation. Therefore, this delicate design may open new horizons and cause a paradigm change for PDT in future cancer therapy.

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOFMS) can be used for rapid detection of bacteria proteins in a crude mixture. It can potentially be used as a tool for bacterial identification based on the mass spectral patterns or the appearance of some characteristic mass peaks. However, there are many experimental parameters that can potentially have a strong effect on the observed mass spectra. The objective of this work is to address the mass spectral reproducibility issue. Several experimental parameters that may affect the MALDI spectra are systematically investigated. Results of spectral comparison from two laboratories with different operators and instrumentation are presented. It is demonstrated that minor variations in the sample/matrix preparation procedures for MALDI and in the experimental conditions used for bacterial protein extraction can result in a significant change in the observed spectra, though a number of peaks are conserved in the spectra obtained under different experimental conditions from the same bacterial sample. These conserved peaks may potentially be used as the biomarkers for bacterial identification. It is stressed that this type of investigation on spectral reproducibility should be carried out for different bacterial species in order to identify the mass spectral peaks that are consistently detected regardless of operator and nominal variations in sample preparation approach.

The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through in situ spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).

It remains a considerable challenge to realize complete tumor suppression and avoid tumor regrowth by rational design of photosensitizers (PSs) to improve their photon utilization. In this Article, we provide a molecular design (Icy-NBF) based on the oxygen-content-regulated deactivation process of excited states. In the presence of overexpressed nitroreductase in hypoxic cancer cells, Icy-NBF is reduced and converted into a molecule with the same skeleton (Icy-NH 2 ), in which the deactivation of the PS under 808 nm light irradiation proceeds via a different pathway: the excited states deactivation pathway of Icy-NBF involves radiative transition and energy transfer between Icy-NBF and O2; as for Icy-NH 2 , the deactivation pathway is attributed to non-radiative relaxation. By varying the O2 concentration in tumor cells, the therapeutic mechanism of Icy-NBF under 808 nm light irradiation can be switched between photodynamic and photothermal therapies, which maximizes the advantages of phototherapies with no tumor regrowth. Our study provides help in designing of smart PSs with improvement of photon utilization for efficient tumor photoablation.

It is accepted that the monolayer ligand shell in monolayer-protected gold nanoclusters (MPCs) plays an important role in stabilizing the metal core structure. Previous reports have shown that the core and shell do not interact chemically, and very few studies investigating the intramolecular charge transfer (ICT) between the core and ligand shell in clusters have been reported. The underlying excited state relaxation mechanisms about the influence of solvents, the optically excited vibration, and the roles of the core and shell in charge transfer remain unknown to a large extent. Here we report a femtosecond transient absorption study of a Au20(SR)16 (R = CH2CH2Ph) cluster in toluene and tetrahydrofuran. The ICT from the outside shell to the inside core upon excitation in Au20(SR)16 is identified. The observed solvation-dependent oscillations in different solvents further confirm the photoinduced ICT formation in Au20(SR)16. The results provide a fundamental understanding of the structure-property relationships about the solvation-dependent core-shell interaction in Au MPCs.

Structure-inherent targeting (SIT) agents are of particular importance for clinical precision medicine; however, there still exists a great lack of SIT phototheranostics for simultaneous cancer diagnosis and targeted photodynamic therapy (PDT). Herein, for the first time, we propose a “one-for-all” strategy by using the Förster resonance energy transfer (FRET) mechanism to construct such omnipotent SIT phototheranostics. Of note, this novel tactic can not only endow conventional sensitizers with highly effective native tumor-targeting potency but also simultaneously improve their photosensitization activities, resulting in dramatically boosted therapeutic index. After intravenous injection of the prepared SIT theranostic, the neoplastic sites are distinctly “lighted up” and distinguished from neighboring tissues, showing a near-infrared signal-to-background ratio value as high as 12.5. More importantly, benefiting from the FRET effect, markedly amplified light-harvesting ability and 1O2 production are demonstrated. Better still, other favorable features are also simultaneously achieved, including specific mitochondria anchoring, augmented cellular uptake (>13-fold), as well as ideal biocompatibility, all of which allow orders-of-magnitude promotion in anticancer efficiency both in vitro and in vivo. We believe this one-for-all SIT platform will provide a new idea for future cancer precision therapy.