Peptide-functionalized delivery vehicles for enhanced cancer therapy.

Functional peptides that are made up of diverse endogenous amino acids with a specific sequence and length have shown various functionalities including specific biological recognition and cell penetrating ability for biomedical applications. Therefore, incorporation of peptide with a certain tailor-made amino acid sequence to the delivery systems has endowed the resulting delivery vehicles with specific functions, which provided a robust strategy for enhancing the therapeutic efficiency for malignant diseases. To make a timely review on this hot subject of research, we summarized the recent progress on peptide-functionalized delivery vehicles for enhanced cancer therapy with an emphasis on the chemistry adopted for the conjugation of peptide compared to most of the published reviews with a focus on the property and performance of the peptide-functionalized delivery systems. The primary synthetic strategies used for peptide conjugation were first summarized. An exhibition of four different types of peptide-functionalized delivery vehicles were next presented following a classification standard of the functions of each peptide category including tumor-targeting peptide, cell-penetrating peptide, subcellular organelle-targeting peptide and tumor-penetrating peptide. A concluding remark on the future direction of this rapidly developing research field was made finally. The important principles on the design of peptide, screening of the conjugation strategy, and optimization of peptide property that were drawn from the detailed comparison of the representative literature in this review will provide useful guidelines for the future development of advanced peptide-functionalized delivery platforms with enhanced therapeutic efficiency for cancer therapy.

Delivery of Liver-Specific miRNA-122 Using a Targeted Macromolecular Prodrug toward Synergistic Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) poses a great threat to human health. The elegant combination of gene therapy and chemotherapy by nanocarriers has been repeatedly highlighted to realize enhanced therapeutic efficacy relative to monotreatment. However, the leading strategy to achieve the efficient codelivery of the gene and drug remains the electrostatic condensation with the nucleic acid and the hydrophobic encapsulation of drug molecules by the nanocarriers, which suffers substantially from premature drug leakage during circulation and severe off-target-associated side effects. To address these issues, we reported in this study the codelivery of liver-specific miRNA-122 and anti-cancer drug 5-fluorouracil (5-Fu) using a macromolecular prodrug approach, that is, electrostatic condensation with miRNA-122 using galactosylated-chitosan-5-fluorouracil (GC-FU). The delivery efficacy was evaluated comprehensively in vitro and in vivo. Specifically, the biocompatibility of GC-FU/miR-122 nanoparticles (NPs) was assessed by hemolysis activity analysis, BSA adsorption test, and cell viability assay in both normal liver cells (L02 cells) and endothelial cells. The resulting codelivery systems showed enhanced blood and salt stability, efficient proliferation inhibition of HCC cells, and further induction apoptosis of HCC cells, as well as downregulated expression of ADAM17 and Bcl-2. The strategy developed herein is thus a highly promising platform for an effective codelivery of miRNA-122 and 5-Fu with facile fabrication and great potential for the clinical translation toward HCC synergistic therapy.

Facile fabrication of a novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the greatest public health problems worldwide, and chemotherapy remains the major approach for the HCC treatment. Doxorubicin (DOX) is one of the anthracycline antibiotics but its clinical use is limited due to its severe cardiotoxicity. In this study, novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates (PDC-NPs) were fabricated for HCC treatment. The stabilized structure of the PDC-NPs was characterized by methylene blue absorption, the size, zeta potential and the morphology, which was investigated by Zetasizer nanoparticle analyzer and transmission electron microscope (TEM), of nanoparticles. The PDC-NPs achieved a sustained and prolonged release ability, which was illustrated with in vitro drug release profiles, anti-cell proliferation study, cellular uptake assay and in vivo pharmacokinetics analysis. Biocompatibility of the PDC-NPs was assessed with bovine serum albumin (BSA) adsorption test, hemolysis activity examination and viability evaluation of human umbilical vein endothelial cells. Importantly, in vivo studies of the PDC-NPs, which were performed in the athymic BALB/c nude mice, demonstrated that the PDC-NPs significantly reduced the lethal side effect of DOX. Additionally, the H&E staining and serum biochemistry study further confirmed the excellent biological security of the PDC-NPs.