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.
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 acidinduced hydrophobicity increase with an arrowp H-response range (from 7.4 to 6.5). In situ self-assembly in the tumor microenvironment at appropriate molecular concentrations (around the IC 50 values of PPCs) enabled drug delivery deeper into the tumor.Acytotoxic peptide KLAK, decorated with the pH-sensitive moiety cis-aconitic anhydride (CAA), and acellpenetrating peptide TATw ere conjugated onto poly(b-thioester) backbones to produce PT-K-CAA,w hich can penetrate deeply into solid tumors owing to its small sizea sas ingle chain. During penetration in vivo,C AA responds to the weak acid, leading to the self-assembly of PPCs and the recovery of therapeutic activity.T herefore,adeep-penetration ability for enhanced cancer therapyi sp rovided by this in vivo assembly strategy.
In this paper we describe and compare the performance of a series of cepstrum-based procedures that enable the CMU SPHINX-II speech recognition system to maintain a high level of recognition accuracy over a wide variety of acoustical environments. We describe the MFCDCN algorithm, an environment-independent extension of the efficient SDCN and FCDCN algorithms developed previously. We compare the performance of these algorithms with the very simple RASTA and cepstral mean normalization procedures, describing the performance of these algorithms in the context of the 1992 DARPA CSR evaluation using secondary microphones, and in the DARPA stress-test evaluation.
The aim of the present study was to screen gastric cancer (GC) tissue and adjacent tissue for differences in mRNA and circular (circRNA) expression, to analyze the differences in circRNA and mRNA expression, and to investigate the circRNA expression in gastric carcinoma and its mechanism. circRNA and mRNA differential expression profiles generated using Agilent microarray technology were analyzed in the GC tissues and adjacent tissues. qRT-PCR was used to verify the differential expression of circRNAs and mRNAs according to the interactions between circRNAs and miRNAs as well as the possible existence of miRNA and mRNA interactions. We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs. The qRT-PCR validation experiments showed that hsa_circRNA_400071, hsa_circRNA_000543 and hsa_circRNA_001959 expression was consistent with the microarray analysis results. ii) 29,112 genes were found in the GC tissues and adjacent tissues, including 5,460 differentially expressed genes. Among them, 2,390 differentially expressed genes were upregulated and 3,070 genes were downregulated. Gene Ontology (GO) analysis of the differentially expressed genes revealed these genes involved in biological process classification, cellular component classification and molecular function classification. Pathway analysis of the differentially expressed genes identified 83 significantly enriched genes, including 28 upregulated genes and 55 downregulated genes. iii) 69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs. The conclusions are: i) differentially expressed circRNAs had corresponding miRNA binding sites. These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC in the future. ii) Differentially expressed genes may be involved in the occurrence of GC via a variety of mechanisms. iii) CD44, CXXC5, MYH9, MALAT1 and other genes may have important implications for the occurrence and development of GC through the regulation, interaction, and mutual influence of circRNA-miRNA-mRNA via different mechanisms.
Nanotherapeutics have encountered some bottleneck problems in cancer therapy, such as poor penetration and inefficient accumulation in tumor site. We herein developed a novel strategy for deep tissue penetration in molecular level and near-infrared (NIR) laser guided in situ self-assembly to solve these challenges. For the proof-of-concept study, we synthesized the polymer−peptide conjugates (PPCs) composed of (i) poly(β-thioester) as thermoresponsive backbone, (ii) functional peptides (cytotoxic peptide and cell-penetrating peptide), and (iii) the NIR molecule with photothermal property. The PPCs in the molecular level with small size (<10 nm) can penetrate deeply into the interior of the tumor at body temperature. Under the irradiation of NIR laser, the temperature rise induced by photothermal molecules led to the intratumoral selfassembly of thermoresponsive PPCs. The resultant spherical nanoparticles can accumulate in tumor and enter cells effectively, inducing cell apoptosis by destroying mitochondria membrane. Through the site-specific size control, a variety of merits of PPCs are realized including deep tumor penetration, enhanced accumulation, and cellular internalization in vivo. Taking advantage of the NIR guided in situ assembly strategy, numerous polymeric or nanoscaled therapeutics with high anticancer activity can be exploited.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.