Emulsion interfacial polymerization of anticancer peptides:fabricating polypeptide nanospheres with high drug-loading efficiency and enhanced anticancer activity

The development of drug delivery systems with high drug-loading efficiency, kinetic stability against dilution, as well as enhanced anticancer activity is of crucial importance to the fields of self-assembly and nanomedicine. Herein, we propose a strategy where the anticancer peptide acts as water-soluble monomer to directly participate in emulsion interfacial polymerization for fabricating polypeptide nanospheres. The constructed polypeptide nanospheres hold a high drug loading efficiency of 77%, and can be stably dispersed in highly diluted aqueous solutions. The acid-labile amide linkage in polypeptide nanospheres can be hydrolyzed in tumor acidic environments, thus releasing anticancer peptides selectively. The polypeptide nanospheres achieve significantly enhanced anticancer activity against HCT116 cells in vitro and in vivo through improved mitochondrial and membrane disruption. In addition, its side effects on normal cells can be reduced significantly. It is highly anticipated that more kinds of anticancer drug candidates or anticancer drugs can be applied to fabricate polymeric nanomedicines with improved anticancer activity through this strategy.

Supramolecular Peptide Therapeutics:Host-Guest Interaction-Assisted Systemic Delivery of Anticancer Peptides

The poor stability of therapeutic peptides in physiological environments hampers their therapeutic efficacy.In this work,a strategy of supramolecular peptide therapeutics(SPT)was proposed for the improvement of the stability and anticancer efficacy of the peptides in vivo.N-Terminal phenylalanine-containing cytotoxic peptides were carried in the cucurbit[7]uril-containing polymer through host–guest interactions between the phenylalanine and cucurbit[7]uril,generating the supramolecular peptide complex with high peptide encapsulation efficiency(>97%).The formation of the supramolecular peptide complex reserved the biological activities of the peptide,presenting prolonged blood circulation and improved anticancer efficacy.This SPT strategy might provide a cucurbituril-and phenylalanine-functionalized approach for the design and the development of peptide-based pharmaceuticals.

Bioactive peptides for anticancer therapies

Cancer is a serious concern in public health worldwide.Numerous modalities including surgery,radiotherapy,and chemotherapy,have been used for cancer therapies in clinic.Despite progress in anticancer therapies,the usage of these methods for cancer treatment is often related to deleterious side effects and multidrug resistance of conventional anticancer drugs,which have prompted the development of novel therapeutic methods.Anticancer peptides(ACPs),derived from naturally occurring and modified peptides,have received great attention in these years and emerge as novel therapeutic and diagnostic candidates for cancer therapies,because of several advantages over the current treatment modalities.In this review,the classification and properties of ACPs,the mode of action and mechanism of membrane disruption,as well as the natural sources of bioactive peptides with anticancer activities were summarised.Because of their high efficacy for inducing cancer cell death,certain ACPs have been developed to work as drugs and vaccines,evaluated in varied phases of clinical trials.We expect that this summary could facilitate the understanding and design of ACPs with increased specificity and toxicity towards malignant cells and with reduced side effects to normal cells.