Programmable Morphology-Adaptive Peptide Nanoassembly for Enhanced Catalytic Therapy.

Nanocatalytic therapy holds significant promise in cancer treatment by exploiting the high oxidative stress within tumor cells. However, efficiently delivering nanocatalytic agents to tumor tissues and maximizing their catalytic activity in situ remain critical challenges. Morphology-adaptive delivery systems, capable of adjusting their physical form in response to physiological conditions, offer unique spatiotemporal control for navigating complex biological environments like the tumor microenvironment.

Tumor-Specific Protein Induced in Situ Self-Assembly of Peptide Drugs for Synergistic Mitochondria Disruption.

Mitochondria-targeted cancer therapy is an effective method for controlling tumor growth. However, the presence of repair mechanisms in tumor cells in response to mitochondrial damage poses significant challenges for treatment. By taking advantage of intracellular self-assembly technology, a peptide nanomaterial, RC-K-FX, that enters tumor cells in a monomeric form is designed.

Self-Assembled Peptide with Morphological Structure for Bioapplication.

Peptide materials, such as self-assembled peptide materials, are very important biomaterials. Driven by multiple interaction forces, peptide molecules can self-assemble into a variety of different macroscopic forms with different properties and functions. In recent years, the research on self-assembled peptides has made great progress from laboratory design to clinical application.

Self-Assembly of Peptides as an Alluring Approach toward Cancer Treatment and Imaging.

Cancer is a severe threat to humans, as it is the second leading cause of death after cardiovascular diseases and still poses the biggest challenge in the world of medicine. Due to its higher mortality rates and resistance, it requires a more focused and productive approach to provide the solution for it. Many therapies promising to deliver favorable results, such as chemotherapy and radiotherapy, have come up with more negatives than positives.

Covalent drugs based on small molecules and peptides for disease theranostics.

Biomacromolecules, such as proteins, nucleic acids and polysaccharides, are widely distributed in the human body, and some of them have been recognized as the targets of drugs for disease theranostics. Drugs typically act on targets in two ways: non-covalent bond and covalent bond. Non-covalent bond-based drugs have some disadvantages, such as structural instability and environmental sensitivity.

Intrinsic Strain-Mediated Ultrathin Ceria Nanoantioxidant.

Metal oxide nanozymes have emerged as the most efficient and promising candidates to mimic antioxidant enzymes for treatment of oxidative stress-mediated pathophysiological disorders, but the current effectiveness is unsatisfactory due to insufficient catalytic performance. Here, we report for the first time an intrinsic strain-mediated ultrathin ceria nanoantioxidant. Surface strain in ceria with variable thicknesses and coordinatively unsaturated Ce sites was investigated by theoretical calculation analysis and then was validated by preparing ∼1.

Sonoactivated Cascade Fenton Reaction Enhanced by Synergistic Modulation of Electron-Hole Separation for Improved Tumor Therapy.

Chemodynamic therapy (CDT) is an emerging targeted treatment technique for tumors via the generation of highly cytotoxic hydroxyl radical (·OH) governed by tumor microenvironment-assisted Fenton reaction. Despite high effectiveness, it faces limitations like low reaction efficiency and limited endogenous H O , compromising its therapeutic efficacy. This study reports a novel platform with enhanced CDT performance by in situ sono-activated cascade Fenton reaction.

Cell membrane-specific self-assembly of peptide nanomedicine induces tumor immunogenic death to enhance cancer therapy.

Immunogenic cell death (ICD), as an unusual cell death pattern, mediates cancer cells to release a series of damage-associated molecular patterns (DAMPs), and is widely used in the field of cancer immunotherapy. Injuring the cell membrane can serve as a novel ICD initiation strategy. In this study, a peptide nanomedicine (PNpC) is designed using the fragment CM11 of cecropin, which is effective in disrupting cell membranes because of its α-helical structure.

Reversible covalent nanoassemblies for augmented nuclear drug translocation in drug resistance tumor.

The drug efflux by P-glycoprotein (P-gp) is the primary contributor of multidrug resistance (MDR), which eventually generates insufficient nuclear drug accumulation and chemotherapy failure. In this paper, reversible covalent nanoassemblies on the basis of catechol-functionalized methoxy poly (ethylene glycol) (mPEG-dop) and phenylboronic acid-modified cholesterol (Chol-PBA) are successfully synthesized for delivery of both doxorubicin (DOX, anti-cancer drug) and tariquidar (TQR, P-glycoprotein inhibitor), which shows efficient nuclear DOX accumulation for overcoming tumor MDR. Through naturally forming phenylboronate linkage in physiological circumstances, Chol-PBA is able to bond with mPEG-dop.

Skin-like wound dressings with on-demand administration based on peptide self-assembly for skin regeneration.

Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF).

An Ultrasound-Induced Self-Clearance Hydrogel for Male Reversible Contraception.

Nearly half of pregnancies worldwide are unintended mainly due to failure of contraception, resulting in negative effects on women's health. Male contraception techniques, primarily condoms and vasectomy, play a crucial role in birth control, but cannot be both highly effective and reversible at the same time. Herein, an ultrasound (US)-induced self-clearance hydrogel capable of real-time monitoring is utilized for injection into the vas deferens, enabling effective contraception and noninvasive recanalization whenever needed.

Intracellular Self-Immolative Polyprodrug with Near-Infrared Light Guided Accumulation and in Vivo Visualization of Drug Release.

The selective accumulation and real-time monitoring of drug release at tumor site are the key bottlenecks to the clinical translation of polyprodrug. Herein, an intracellular self-immolative polyprodrug (PMTO) is exploited, which not only shows the enhanced cellular internalization and selective accumulation in tumor site under the mild hyperthermia triggered by laser irradiation, but also possesses the self-monitoring drug release ability in vivo. The polyprodrug amphiphiles are synthesized by sequential esterification reaction, and hydrophilic poly(ethylene glycol) serves as blocking agent.

In Vivo Self-Assembly Induced Cell Membrane Phase Separation for Improved Peptide Drug Internalization.

Therapeutic peptides have been widely concerned, but their efficacy is limited by the inability to penetrate cell membranes, which is a key bottleneck in peptide drugs delivery. Herein, an in vivo self-assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization. A phosphopeptide KYp is synthesized, containing an anticancer peptide [KLAKLAK] (K) and a responsive moiety phosphorylated Y (Yp).

Regulating Twisted Skeleton to Construct Organ-Specific Perylene for Intensive Cancer Chemotherapy.

The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ-specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ-specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ-specificity and present an example of lung-specific distribution on the basis of bay-twisted PDIC-NC.

Hybrid Plasmonic Nanodumbbells Engineering for Multi-Intensified Second Near-Infrared Light Induced Photodynamic Therapy.

Photodynamic therapy (PDT) has shown great potential in infection treatment. However, the shallow depth of the short wavelength light and the low reactive oxygen species (ROS) production hinder its development. A strategy that can achieve a second near-infrared (NIR-II) light that is a long wavelength induced multi-intensified antibacterial PDT is most critical.

Precise magnetic resonance imaging-guided sonodynamic therapy for drug-resistant bacterial deep infection.

The precise treatment of drug-resistant deep bacterial infections remains a huge challenge in clinic. Herein, a polymer-peptide-porphyrin conjugate (PPPC), which can be real-time monitored in infectious site, is developed for accurate and deep sonodynamic therapy (SDT) based on "in vivo self-assembly" strategy. The PPPC contains four moieties, i.

Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy.

In some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), including (1) the singlet oxygen O is generated by P18, (2) the thioketal bond is cleaved by the O, (3) the departure of PEG chains leads to the in situ self-assembly, and (4) the resultant self-assembled PK nanoparticles show considerable cellular internalization. Owing to the synergistic effect of US on increasing the membrane permeability, the endocytosis and lysosome escape of PK nanoparticles are further enhanced effectively, resulting in the improved therapeutic efficacy.

Near-Infrared Laser-Triggered Dimorphic Transformation of BF-Azadipyrromethene Nanoaggregates for Enhanced Solid Tumor Penetration.

The shape of a drug delivery system impacts its behavior such as circulation time, accumulation, and penetration. Considering the advantages of functional dyes in bioapplications, we synthesize a class of nanoaggregates based on BF-azadipyrromethene (aza-BODIPY) dyes, which can realize long blood circulation and deep tumor penetration simultaneously through morphological transformation modulated by a near-infrared (NIR) laser. First, when the temperature increases, the wormlike nanofibers of the aza-BODIPY-1 aggregate, possessing a long blood circulation time, can be transformed into spherical nanoparticles, which are conducive to increasing the penetration in the solid tumor.

Photothermal-Promoted Morphology Transformation Monitored by Photoacoustic Imaging.

The construction of the nanoassembly has been demonstrated to improve the performance of bioactive molecules, but the control of the morphology of nanomaterials still remains a tremendous challenge. Herein, a photothermal-promoted morphology transformation (PMT) strategy is developed to accelerate the formation of nanomaterials for improving the biological performance of drug molecules. Compared with the spontaneous process, the rate of transformation increases by ∼4 times in the PMT process.

Site-Specific Construction of Long-Term Drug Depot for Suppression of Tumor Recurrence.

Local tumor recurrence after surgical resection is a critical concern in cancer therapy, and the current treatments, such as postsurgical chemotherapy, still show undesired side effects. Here a nonimplant strategy (transformation induced localization, TIL) is presented to in situ construct long-term retentive drug depots, wherein the sustained drug release from fibrous drug depots results in highly efficient suppression of postsurgical local tumor relapse. The peptide-based prodrug nanoparticles show favorable tumor targeting and instantly reorganize into fibrous nanostructures under overexpressed enzyme, realizing the construction of long-term drug depot in the tumor site.

Endogenous Reactive Oxygen Species-Triggered Morphology Transformation for Enhanced Cooperative Interaction with Mitochondria.

The morphology controlled molecular assemblies play vital roles in biological systems. Here we present endogenous reactive oxygen species (ROS)-triggered morphology transformation of polymer-peptide conjugates (PPCs) for cooperative interaction with mitochondria, exhibiting high tumor therapeutic efficacy. The PPCs are composed of (i) a β-sheet-forming peptide KLVFF conjugated with poly(ethylene glycol) through ROS-cleavable thioketal, (ii) a mitochondria-targeting cytotoxic peptide KLAK, and (iii) a poly(vinyl alcohol) backbone.