Photodynamic therapy is arising as a noninvasive treatment modality for cancer and other diseases. One of the key factors to determine the therapeutic function is the efficiency of photosensitizers (PSs). Opposed to traditional PSs, which show quenched fluorescence and reduced singlet oxygen production in the aggregate state, PSs with aggregation-induced emission (AIE) exhibit enhanced fluorescence and strong photosensitization ability in nanoparticles. Here, the design principles of AIE PSs and their biomedical applications are discussed in detail, starting with a summary of traditional PSs, followed by a comparison between traditional and AIE PSs to highlight the various design strategies and unique features of the latter. Subsequently, the applications of AIE PSs in photodynamic cancer cell ablation, bacteria killing, and image-guided therapy are discussed using charged AIE PSs, AIE PS molecular probes, and AIE PS nanoparticles as examples. These studies have demonstrated the great potential of AIE PSs as effective theranostic agents to treat tumor or bacterial infection. This review hopefully will spur more research interest in AIE PSs for future translational research.

Photosensitizers with Aggregation-Induced Emission: Materials and Biomedical Applications

Cell-penetrating peptides (CPPs) are short peptides (fewer than 30 amino acids) that have been predominantly used in basic and preclinical research during the last 30 years. Since they are not only capable of translocating themselves into cells but also facilitate drug or CPP/cargo complexes to translocate across the plasma membrane, they have potential applications in the disease diagnosis and therapy, including cancer, inflammation, central nervous system disorders, otologic and ocular disorders, and diabetes. However, no CPPs or CPP/cargo complexes have been approved by the US Food and Drug Administration (FDA). Many issues should be addressed before translating CPPs into clinics. In this review, we summarize recent developments and innovations in preclinical studies and clinical trials based on using CPP for improved delivery, which have revealed that CPPs or CPP-based delivery systems present outstanding diagnostic therapeutic delivery potential.

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Cell-Penetrating Peptides in Diagnosis and Treatment of Human Diseases: From Preclinical Research to Clinical Application

Coordination-driven suprastructures have attracted much interest due to their unique properties. Among these structures, platinum-based architectures have been broadly studied due to their facile preparation. The resultant two- or three-dimensional (2D or 3D) systems have many advantages over their precursors, such as improved emission tuning, sensitivity as sensors, and capture and release of guests, and they have been applied in biomedical diagnosis as well as in catalysis. Herein, we review the recent results related to platinum-based coordination-driven self-assembly (CDSA), and the text is organized to emphasizes both the synthesis of new metallacycles and metallacages and their various applications.

Recent developments in the construction and applications of platinum-based metallacycles and metallacages via coordination

https://escholarship.org/content/qt3wt0t6bf/qt3wt0t6bf.pdf?t=qd1b1k

Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications.

The Blood-Brain Barrier (BBB), a unique structure in the central nervous system (CNS), protects the brain from bloodborne pathogens by its excellent barrier properties. Nevertheless, this barrier limits therapeutic efficacy and becomes one of the biggest challenges in new drug development for neurodegenerative disease and brain cancer. Recent breakthroughs in nanotechnology have resulted in various nanoparticles (NPs) as drug carriers to cross the BBB by different methods. This review presents the current understanding of advanced NP-mediated non-invasive drug delivery for the treatment of neurological disorders. Herein, the complex compositions and special characteristics of BBB are elucidated exhaustively. Moreover, versatile drug nanocarriers with their recent applications and their pathways on different drug delivery strategies to overcome the formidable BBB obstacle are briefly discussed. In terms of significance, this paper provides a general understanding of how various properties of nanoparticles aid in drug delivery through BBB and usher the development of novel nanotechnology-based nanomaterials for cerebral disease therapies.

Overcoming blood–brain barrier transport: Advances in nanoparticle-based drug delivery strategies

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.

https://www.pnas.org/content/pnas/116/47/23437.full.pdf

Membrane intercalation-enhanced photodynamic inactivation of bacteria by a metallacycle and TAT-decorated virus coat protein

3D-printable supramolecular hydrogels with shear-thinning property: fabricating strength tunable bioink via dual crosslinking.

Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/G...

Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus-Inspired Gene-Silencing Technology

A perspective on general direction and challenges facing antimicrobial peptides

Pseudomonas aeruginosa (P. aeruginosa) biofilms are associated with a wide range of infections, from chronic tissue diseases to implanted medical devices. In a biofilm, the extracellular polymeric substance (EPS) causes an inhibited penetration of antibacterial agents, leading to a 100-1000 times tolerance of the bacteria. In view of the water-filled channels in biofilms and the highly negative charge of EPS, we design a chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13) in this study. The CS-PEG-LK13 prefers a neutrally charged assembly at a size of ∼100 nm in aqueous environment, while undergoes disassembly to expose the α-helical peptide at the bacterial cell membrane. This behavior provides CS-PEG-LK13 superiorities in both penetrating the biofilms and inactivating the bacteria. At a concentration of 8 times the minimum inhibitory concentration, CS-PEG-LK13 has a much higher antibacterial efficiency (72.70%) than LK13 peptide (15.24%) and tobramycin (33.57%) in an in vitro P. aeruginosa biofilm. Moreover, CS-PEG-LK13 behaves comparable capability of combating an implanted P. aeruginosa biofilm to highly excess tobramycin. This work has implications for the design of new antibacterial agents in biofilm combating.

Meng Zhu

Papers

Membrane intercalation-enhanced photodynamic inactivation of bacteria by a metallacycle and TAT-decorated virus coat protein

3D-printable supramolecular hydrogels with shear-thinning property: fabricating strength tunable bioink via dual crosslinking.

Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus-Inspired Gene-Silencing Technology

A perspective on general direction and challenges facing antimicrobial peptides

Combating Pseudomonas aeruginosa Biofilms by a Chitosan-PEG-Peptide Conjugate via Changes in Assembled Structure.