<p>Amylase-Protected Ag Nanodots for in vivo Fluorescence Imaging and Photodynamic Therapy of Tumors</p>

Abstract

Background: Fluorescent metallic nanodots (NDs) have become a promising nanoprobe for a wide range of biomedical applications. Because Ag NDs have a high tendency to be oxidized, their synthesis and storage are a big challenge. Thus, the method for preparing stable Ag NDs is urgently needed. Surface modification and functionalization can enrich the capability of Ag NDs. Methods: In this work, fluorescent Ag NDs were synthesized in deoxygenated water by using porcine pancreatic α-amylase (PPA) as the stabilizing/capping agent. The absorption and fluorescence of PPA-protected Ag NDs (PPA@AgNDs) were measured with a spectrophotometer and a spectrofluorometer, respectively. The morphology of PPA@AgNDs was characterized by high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM). The biocompatibility of PPA@AgNDs was evaluated by tetrazolium (MTT)-based assay. PolyLys-Cys-SH (sequence: KKKKKKC) peptides were conjugated to PPA@AgNDs via heterobifunctional crosslinkers. PolyLys-Cys-linked PPA@AgNDs absorbed 5-aminolevulinic acid (ALA) by electrostatic interaction at physiological pH. The capability of tumor targeting was evaluated by intravenously injecting PPA@AgND-ALA into 4T1 breast cancer xenograft mouse models. Photodynamic therapy (PDT) against tumors was performed under 635 nm laser irradiation. Results: PPA@AgNDs emitted at 640 nm with quantum yield of 2.1%. The Ag NDs exhibited strong photostability over a long period and a fluorescence lifetime of 5.1 ns. PPA@AgNDs easily entered the cells to stain the nuclei, showing the capabilities of living cell imaging with negligible cytotoxicity. ALA-loaded PPA@AgNDs (PPA@AgND-ALA) presented the superiority of passive tumor targeting via the enhanced permeability and retention (EPR) effect. Tumors were visualized in the near-infrared (NIR) region with reduced background noise. ALA molecules released from PPA@AgND-ALA was converted into the photosensitizer (PS) of protoporphyrin IX (PpIX) intracellularly and intratumorally, which greatly improved the PDT efficacy. Conclusion: Our approach opens a new way to design a novel theranostic nanoplatform of PPA@AgND-ALA for effective tumor targeting and fluorescence image-guided PDT.

Oxidative Stimuli‐Responsive “Pollen‐Like” Exosomes from Silver Nanoflowers Remodeling Diabetic Wound Microenvironment for Accelerating Wound Healing

“…However, H 2 O 2 pretreatment significantly accelerated the Ag + release of Ag@BSA NFs (≈2.0-39.2%) within 12 days, which demonstrated the ROS-responsive degradation behavior of Ag@BSA NFs. Similar to the previous reports, this result suggested that Ag@ BSA NPs could acquire antimicrobial activity by releasing active Ag + ions, [19,20] which bind strongly to the electron donor groups in biological molecules. Fourier transform infrared spectroscopy (FTIR) revealed O-H and N-H stretching vibration peak at 3415 cm −1 , and the protein bands at 1650 and 1540 cm −1 (Figure 2f), confirming the presence of BSA onto the surface of Ag@BSA NFs.…”

“…Owing to the intrinsic toxic effects of the remaining cores of Ag NPs, Ag + -based antimicrobial agents have been utilized as a potential alternative to entire Ag NPs for antibacterial applications. [17][18][19] Although exciting, these materials present an uncontrollable release of Ag + and an "always-on" state regardless of the disease microenvironment, resulting in poor therapeutic selectivity and off-target toxicity to the healthy tissues. Besides, recent studies have suggested that the overuse of Ag + could induce resistance [20] and pose adverse systemic effects, including oral toxicity, liver and kidney damage.…”

Carrier‐Free Delivery of Ultrasmall π‐Conjugated Oligomer Nanoparticles with Photothermal Conversion over 80% for Cancer Theranostics

“…These results further demonstrated that carrier-free DCF-P possessed better photothermal capacity, and the PCE enhancement would be mainly rooted from highly ordered molecular arrangement (Figure S3, Supporting Information) and the promoted non-radiative transition. [54,[56][57][58] The concentration and powerdependent temperature rises of DCF-P and DCF-M were further confirmed (Figures S7 and S8, Supporting Information). Significantly, after five heating/cooling cycles of 660 nm laser irradiation (1.0 W cm −2 ), both of DCF-P and DCF-M remained almost unchanged temperature increasing (Figure 1F), and sizes and maximal absorption peaks of the nanoparticles displayed negligible changes before and after laser irradiation (Figure S9, Supporting Information), highlighting their good photothermal stability.…”

Conjugated Polymers: Optical Toolbox for Bioimaging and Cancer Therapy

“…Therefore, the generating cytotoxic ROS can induce the ablation of cancer cells through multifaceted mechanisms, mainly leading to necrosis and/or apoptosis, the damage of tumor microvessel, and immune response. [156][157][158][159] Over the past decades, PDT has been extensively exploited as a promising modality of cancer treatment owing to its high spatiotemporal precision. [160] Importantly, since the first approval [150] Copyright 2012, Wiley-VCH.…”