Saran Long

Bio: Saran Long is an academic researcher from Dalian University of Technology. The author has contributed to research in topics: Photodynamic therapy & Photosensitizer. The author has an hindex of 16, co-authored 43 publications receiving 1035 citations.

Near-Infrared Light-Initiated Molecular Superoxide Radical Generator: Rejuvenating Photodynamic Therapy against Hypoxic Tumors

Abstract: 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 (O2–•) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O2–• 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% O2), ENBS-B can generate considerable O2–• through type I photoreactions, and partial O2–• is transformed to high toxic OH· through SOD-mediated 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 achieve...

NIR Light-Driving Barrier-Free Group Rotation in Nanoparticles with an 88.3% Photothermal Conversion Efficiency for Photothermal Therapy.

Abstract: 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.

Aminopeptidase N Activatable Fluorescent Probe for Tracking Metastatic Cancer and Image-Guided Surgery via in Situ Spraying

Abstract: 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).

De Novo Design of Phototheranostic Sensitizers Based on Structure-Inherent Targeting for Enhanced Cancer Ablation.

Abstract: 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 Forster 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 dem...

Synthesis of Copper Peroxide Nanodots for H2O2 Self-Supplying Chemodynamic Therapy.

Abstract: Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H2O2 into hydroxyl radical (•OH), but endogenous H2O2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H2O2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2. The CP nanodots were prepared through coordination of H2O2 to Cu2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.

Recent progresses in small-molecule enzymatic fluorescent probes for cancer imaging

Abstract: Abnormal enzymatic activities are directly related to the development of cancers. Identifying the location and expression levels of these enzymes in live cancer cells have considerable importance in early-stage cancer diagnoses and monitoring the efficacy of therapies. Small-molecule fluorescent probes have become a powerful tool for the detection and imaging of enzymatic activities in biological systems by virtue of their higher sensitivity, nondestructive fast analysis, and real-time detection abilities. Moreover, due to their structural tailorability, numerous small-molecule enzymatic fluorescent probes have been developed to meet various demands involving real-time tracking and visualizing different enzymes in live cancer cells or in vivo. In this review, we provide an overview of recent advances in small-molecule enzymatic fluorescent probes mainly during the past decade, including the design strategies and applications for various enzymes in live cancer cells. We also highlight the challenges and opportunities in this rapidly developing field of small-molecule fluorescent probes for interventional surgical imaging, as well as cancer diagnosis and therapy.

Synthetic ratiometric fluorescent probes for detection of ions

Abstract: Metal cations and anions are essential for versatile physiological processes. Dysregulation of specific ion levels in living organisms is known to have an adverse effect on normal biological events. Owing to the pathophysiological significance of ions, sensitive and selective methods to detect these species in biological systems are in high demand. Because they can be used in methods for precise and quantitative analysis of ions, organic dye-based ratiometric fluorescent probes have been extensively explored in recent years. In this review, recent advances (2015-2019) made in the development and biological applications of synthetic ratiometric fluorescent probes are described. Particular emphasis is given to organic dye-based ratiometric fluorescent probes that are designed to detect biologically important and relevant ions in cells and living organisms. Also, the fundamental principles associated with the design of ratiometric fluorescent probes and perspectives about how to expand their biological applications are discussed.