Self‐assembled nanomaterials show potential high efficiency as theranostics for high‐performance bioimaging and disease treatment. However, the superstructures of pre‐assembled nanomaterials may ...change in the complicated physiological conditions, resulting in compromised properties and/or biofunctions. Taking advantage of chemical self‐assembly and biomedicine, a new strategy of “in vivo self‐assembly” is proposed to in situ construct functional nanomaterials in living subjects to explore new biological effects. Herein, recent advances on peptide‐based nanomaterials constructed by the in vivo self‐assembly strategy are summarized. Modular peptide building blocks with various functions, such as targeting, self‐assembly, tailoring, and biofunctional motifs, are employed for the construction of nanomaterials. Then, self‐assembly of these building blocks in living systems to construct various morphologies of nanostructures and corresponding unique biological effects, such as assembly/aggregation‐induced retention (AIR), are introduced, followed by their applications in high‐performance drug delivery and bioimaging. Finally, an outlook and perspective toward future developments of in vivo self‐assembled peptide‐based nanomaterials for translational medicine are concluded.
Taking inspiration from self‐assembly systems in nature, a new strategy of “in vivo self‐assembly” is proposed to in situ construct functional nanomaterials in living subjects. This concept, from the modular molecular design, assembly driving forces, morphology control, and biological effects to biomedical applications, is discussed.
In cancer treatment, the unsatisfactory solid‐tumor penetration of nanomaterials limits their therapeutic efficacy. We employed an in vivo self‐assembly strategy and designed polymer–peptide ...conjugates (PPCs) that underwent an acid‐induced hydrophobicity increase with a narrow pH‐response range (from 7.4 to 6.5). In situ self‐assembly in the tumor microenvironment at appropriate molecular concentrations (around the IC50 values of PPCs) enabled drug delivery deeper into the tumor. A cytotoxic peptide KLAK, decorated with the pH‐sensitive moiety cis‐aconitic anhydride (CAA), and a cell‐penetrating peptide TAT were conjugated onto poly(β‐thioester) backbones to produce PT‐K‐CAA, which can penetrate deeply into solid tumors owing to its small size as a single chain. During penetration in vivo, CAA responds to the weak acid, leading to the self‐assembly of PPCs and the recovery of therapeutic activity. Therefore, a deep‐penetration ability for enhanced cancer therapy is provided by this in vivo assembly strategy.
Reaching new depths: Polymer–peptide conjugates (PPCs) designed to undergo an acid‐induced increase in hydrophobicity with a narrow pH‐response range (from pH 7.4 to 6.5) underwent in vivo self‐assembly in the tumor microenvironment (see picture). The PPCs in single‐chain form can penetrate deeply into the tumor and self‐assemble into nanoaggregates at molecular concentrations around the IC50 values of the PPCs for enhanced cancer therapy.
•Mass loss increased with increase of coal particle size during pyrolysis in TGA.•Effect of coal particle size and heating rate on the characteristic parameters of coal pyrolysis was ...distinguished.•Tin, Tmax and Tf displayed the logistic distribution along with heating rate up to 1000K/min.•The yields of all the gas species at maximum releasing rate enhanced with increasing the heating rate.•A mechanism corresponding to metaplast forming was proposed to explain the experimental results reasonably.
In this work, thermal behavior of five different coal particle fractions were investigated using thermogravimetric analyzer (TGA) under various heating rates with the maximum of 1000K/min. An on–line Fourier Transform Infrared Spectrometry (FTIR) was employed to evaluate the evolution characteristics of the gaseous products. The results showed that the coal particle size remarkably affected the mass loss and the ash amount. The larger the particle size was, the higher mass loss and the more ash could be, which revealed its high pyrolysis reactivity. In addition, with increasing the particle size, the initial devolatilization temperature (Tin) and devolatilization index (Di) increased, whereas, the final devolatilization temperature (Tf) decreased. This phenomenon was explained by a proposed mechanism of the obstacle escaping of volatiles from the interparticles corresponding to forming large block unit of metaplast. The heating rate has significant effect on the performance of devolatilization profiles and gaseous products releasing. Tin, Tmax and Tf displayed the logistic distribution along with heating rate up to 1000K/min, whereas, Rmax and the heating rate were highly linear correlated with different particle fractions. The enhanced yield at maximum releasing rate for all the gas species were observed with increasing the heating rate. Moreover, the peak of maximum releasing rate on the evolving profiles of gaseous products became narrower and sharper, and releasing time of the gaseous products reduced extremely with increasing the heating rate. These findings can provide fundamental data for practical applications, plant designing, handling, and modeling of integrated coal fluidized bed gasification system as well as other coal fluidized bed pyrolysis/gasification process.
Cerebral amyloid β-peptide (Aβ) accumulation resulting from an imbalance between Aβ production and clearance is one of the most important causes in the formation of Alzheimer's disease (AD). In order ...to preserve the maintenance of Aβ homeostasis and have a notable AD therapy, achieving a method to clear up Aβ plaques becomes an emerging task. Herein, we describe a self-destructive nanosweeper based on multifunctional peptide-polymers that is capable of capturing and clearing Aβ for the effective treatment of AD. The nanosweeper recognize and bind Aβ via co-assembly through hydrogen bonding interactions. The Aβ-loaded nanosweeper enters cells and upregulates autophagy thus promoting the degradation of Aβ. As a result, the nanosweeper decreases the cytotoxicity of Aβ and rescues memory deficits of AD transgenic mice. We believe that this resourceful and synergistic approach has valuable potential as an AD treatment strategy.
The precise and highly efficient drug delivery of nanomedicines into lesions remains a critical challenge in clinical translational research. Here, an autocatalytic morphology transformation platform ...is presented for improving the tumor-specific accumulation of drugs by kinetic control. The in situ reorganization of prodrug from nanoparticle to β-sheet fibrous structures for targeted accumulation is based on nucleation-based growth kinetics. During multiple administrations, the autocatalytic morphology transformation can be realized for skipping slow nucleating process and constructing the bulky nanoassembly instantaneously, which has been demonstrated to induce the cumulative effect of prodrug. Furthermore, the sustained drug release from fibrous prodrug depot in the tumor site inhibits the tumor growth efficiently. The autocatalytic morphology transformation strategy in vivo offers a novel perspective for targeted delivery strategy by introducing chemical kinetics and shows great potential in disease theranostics.
The use of nanoparticles as a potential building block for photosensitizers has recently become a focus of interest in the field of photocatalysis and photodynamic therapy. Porphyrins and their ...derivatives are effective photosensitizers due to extended π-conjugated electronic structure, high molar absorption from visible to near-infrared spectrum, and high singlet oxygen quantum yields as well as chemical versatility. In this paper, we report a synthesis of self-assembled porphyrin nanoparticle photosensitizers using zinc meso-tetra(4-pyridyl)porphyrin (ZnTPyP) through a confined noncovalent self-assembly process. Scanning electron microscopy reveals formation of monodisperse cubic nanoparticles. UV–vis characterizations reveal that optical absorption of the nanoparticles exhibits a red shift due to noncovalent self-assembly of porphyrins, which not only effectively increase intensity of light absorption but also extend light absorption broadly covering visible light for enhanced photodynamic therapy. Electron spin-resonance spectroscopy (ESR) studies show the resultant porphyrin nanoparticles release a high yield of singlet oxygen. Nitric oxide (NO) coordinates to central metal Zn ions to form stabilized ZnTPyP@NO nanoparticles. We show that under light irradiation ZnTPyP@NO nanoparticles release highly reactive peroxynitrite molecules that exhibit enhanced antibacterial photodynamic therapy (APDT) activity. The ease of the synthesis of self-assembled porphyrin nanoparticles and light-triggered release of highly reactive moieties represent a completely different photosensitizer system for APDT application.
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. We further demonstrate that PDIC‐NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2O2 and .OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC‐NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof‐of‐concept demonstration of twisted perylene to well attain lung‐specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.
Herein we modulate the perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of a twisted perylene PDIC‐NC. The in vitro and in vivo biological functions of PDIC‐NC are demonstrated and its molecular mechanism for the inhibiting activity on tumour cells is revealed.
With the increasing incidence and mortality rate, cervical cancer has been considered one of the most frequent malignant tumors in females. Exploration of tumor progression‐related biomarkers could ...facilitate the identification of novel and targeted therapy strategies. To assess the significance of lncRNA AATBC (AATBC) and its potential regulatory mechanism in cervical cancer, and to identify a potential biomarker, this study enrolled 123 patients with cervical cancer. Paired tissue samples were collected. The expression levels of AATBC and miR‐1245b‐5p were analyzed by RT‐qPCR and their significance in the development and prognosis of cervical cancer was evaluated using chi‐square and Cox analyses. In vitro, the regulatory effect of AATBC on the cellular processes of cervical cancer was estimated by CCK8 and Transwell assay. The interaction between ATTBC and miR‐1245b‐5p was assessed by luciferase reporter assay. Significant upregulation of AATBC and reduced miR‐1245b‐5p level in cervical cancer were observed, which showed a negative correlation between their expression levels. Close relationships of AATBC and miR‐1245b‐5p with the FIGO stage and lymph node metastasis were revealed. AATBC showed a significant prognostic value and miR‐1245b‐5p was found to mediate the tumor inhibitory effect of AATBC knockdown, which is speculated to be the underlying molecular mechanism of AATBC in cervical cancer development. Upregulation of AATBC indicted the malignant development and adverse prognosis of cervical cancer. AATBC served as a tumor promoter of cervical cancer by modulating miR‐1245b‐5p.
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 KLAKLAK2 (K) and a responsive moiety phosphorylated Y (Yp). After interacting with alkaline phosphatase (ALP), KYp can be dephosphorylated and self‐assembles in situ, which induces the aggregation of ALP and the protein‐lipid phase separation on cell membrane. Consequently, KYp internalization is 2‐fold enhanced compared to non‐responsive peptide, and IC50 value of KYp is approximately 5 times lower than that of free peptide. Therefore, the in vivo self‐assembly induced phase separation on cell membrane promises a new strategy to improve the drug delivery efficacy in cancer therapy.
An in vivo self‐assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization and anticancer efficacy. KYp self‐assembles in situ, which induces the aggregation of ALP and the protein‐lipid phase separation and leakage on the cell membrane. The peptide drugs internalization is 2‐fold enhanced compared to non‐responsive peptide nanoparticle.
To date, numerous nanosystems have been developed as antibiotic replacements for bacterial infection treatment. However, these advanced systems are limited owing to their nontargeting accumulation ...and the consequent side effects. Herein, transformable polymer–peptide biomaterials have been developed that enable specific accumulation in the infectious site and long‐term retention, resulting in enhanced binding capability and killing efficacy toward bacteria. The polymer–peptide conjugates are composed of a chitosan backbone and two functional peptides, i.e., an antimicrobial peptide and a poly(ethylene glycol)‐tethered enzyme‐cleavable peptide (CPC‐1). The CPC‐1 initially self‐assembles into nanoparticles with pegylated coronas. Upon the peptides are cleaved by the gelatinase secreted by a broad spectrum of bacterial species, the resultant compartments of nanoparticles spontaneously transformed into fibrous nanostructures that are stabilized by enhanced chain–chain interaction, leading to exposure of antimicrobial peptide residues for multivalent cooperative electrostatic interactions with bacterial membranes. Intriguingly, the in situ morphological transformation also critically improves the accumulation and retention of CPC‐1 in infectious sites in vivo, which exhibits highly efficient antibacterial activity. This proof‐of‐concept study demonstrates that pathological environment‐driven smart self‐assemblies may provide a new idea for design of high‐performance biomaterials for disease diagnostics and therapeutics.
Transformable chitosan–peptide biomaterials (CPC‐1) initially self‐assemble into nanoparticles with PEGylated coronas. Upon cleavage of the peptides by gelatinase, the resultant compartments of the nanoparticles spontaneously transform into fibrous nanostructures. The in situ morphological transformation critically improves the accumulation and retention of CPC‐1 in infectious sites in vivo, which exhibits highly efficient antibacterial activity.
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