Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells. A single-dose injection of MRD hydrogel retarded the growth of primary melanoma tumors by more than 95% due to loaded melittin and DOX, with concomitant recruitment of activated natural killer cells in the tumors. Furthermore, MRD hydrogel can activate dendritic cells of draining lymph nodes, specifically deplete M2-like tumor-associated macrophages (TAMs), and produce active, cytotoxic T cells to further defend the cells against remaining tumors, providing potent anticancer efficacy a...

Tumor Ablation and Therapeutic Immunity Induction by an Injectable Peptide Hydrogel.

Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine, from drug delivery and biomaterials to new therapeutic paradigms. Here we discuss the various production methods for this class of compounds, and the characterization, nanomorphologies, and application of their self-assembled nanostructures. We include the most recent findings on their remarkable properties, which hold substantial promise for the creation of the next generation nanomedicines.

/pdf/the-phe-phe-motif-for-peptide-self-assembly-in-nanomedicine-28ibmdkxwc.pdf

The Phe-Phe motif for peptide self-assembly in nanomedicine

Pectin polymers for colon-targeted antitumor drug delivery.

Infection of multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, brings public health issues and causes economic burden. Pathogenic bacteria develop several methods to resist antibiotic killing or inhibition, such as mutation of antibiotic function sites, activation of drug efflux pumps, and enzyme-mediated drug degradation. Antibiotic resistance components can be transferred between bacteria by mobile genetic elements including plasmids, transposons, and integrons, as well as bacteriophages. The development of antibiotic resistance limits the treatment options for bacterial infection, especially for MDR bacteria. Therefore, novel or alternative antibacterial agents are urgently needed. Antimicrobial peptides (AMPs) display multiple killing mechanisms against bacterial infections, including directly bactericidal activity and immunomodulatory function, as potential alternatives to antibiotics. In this review, the development of antibiotic resistance, the killing mechanisms of AMPs, and especially, the design, optimization, and delivery of AMPs are reviewed. Strategies such as structural change, amino acid substitution, conjugation with cell-penetration peptide, terminal acetylation and amidation, and encapsulation with nanoparticles will improve the antimicrobial efficacy, reduce toxicity, and accomplish local delivery of AMPs. In addition, clinical trials in AMP studies or applications of AMPs within the last five years were summarized. Overall, AMPs display diverse mechanisms of action against infection of pathogenic bacteria, and future research studies and clinical investigations will accelerate AMP application.

/pdf/antimicrobial-peptides-from-design-to-clinical-application-13szirhd.pdf

Antimicrobial Peptides: From Design to Clinical Application

Tailoring supramolecular short peptide nanomaterials for antibacterial applications

Self-assembled peptide nanomaterials display the advantageous properties of injectability, biodegradability and biocompatibility. These peptide nanomaterials, by self-assembling, can be widely applied in such fields as drug delivery (small molecules and large molecules), regenerative medicine and nanobiotechnology. In this review, we mainly discuss the properties of these peptide nanomaterials in their physical, chemical and biological aspects. Also discussed are recent advances in their potential applications as drug delivery systems and for uses in regenerative medicine. These current advances show a bright future for the development and clinical applications of self-assembled peptide-based nanotechnology and nanomedicine. However, there are still some big challenges for us to face before these peptide nanomaterials eventually can be used for the treatment of human diseases.

Progress in Self-assembling Peptide-based Nanomaterials for Biomedical Applications.

The development of slow release nano-sized carriers for efficient antineoplastic drug delivery with a biocompatible and biodegradable pectin-based macromolecular pro-drug for tumor therapy has been reported in this study. Pectin-doxorubicin conjugates (PDC), a macromolecular pro-drug, were prepared via an amide condensation reaction, and a novel amphiphilic core-shell micell based on a PDC macromolecular pro-drug (PDC-M) was self-assembled in situ, with pectin as the hydrophilic shell and doxorubicin (DOX) as the hydrophobic core. Then the chemical structure of the PDC macromolecular pro-drug was identified by both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR), and proved that doxorubicin combined well with the pectin and formed macromolecular pro-drug. The PDC-M were observed to have an unregularly spherical shape and were uniform in size by scanning electron microscopy (SEM). The average particle size of PDC-M, further measured by a Zetasizer nanoparticle analyzer (Nano ZS, Malvern Instruments), was about 140 nm. The encapsulation efficiency and drug loading were 57.82% ± 3.7% (n = 3) and 23.852% ±2.3% (n = 3), respectively. The in vitro drug release behaviors of the resulting PDC-M were studied in a simulated tumor environment (pH 5.0), blood (pH 7.4) and a lysosome media (pH 6.8), and showed a prolonged slow release profile. Assays for antiproliferative effects and flow cytometry of the resulting PDC-M in HepG2 cell lines demonstrated greater properties of delayed and slow release as compared to free DOX. A cell viability study against endothelial cells further revealed that the resulting PDC-M possesses excellent cell compatibilities and low cytotoxicities in comparison with that of the free DOX. Hemolysis activity was investigated in rabbits, and the results also demonstrated that the PDC-M has greater compatibility in comparison with free DOX. This shows that the resulting PDC-M can ameliorate the hydrophobicity of free DOX. This work proposes a novel strategy for in-situ one-step synthesis of macromolecular pro-drugs and fabrication of a core-shell micelle, demonstrating great potential for cancer chemotherapy.

The In-Situ One-Step Synthesis of a PDC Macromolecular Pro-Drug and the Fabrication of a Novel Core-Shell Micell.

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Progress in Self-assembling Peptide-based Nanomaterials for Biomedical Applications.

The In-Situ One-Step Synthesis of a PDC Macromolecular Pro-Drug and the Fabrication of a Novel Core-Shell Micell.