Tumor-homing peptide iRGD-conjugate enhances tumor accumulation of camptothecin for colon cancer therapy.

Poor intracellular uptake of therapeutics in the tumor parenchyma is a key issue in cancer therapy. We describe a novel approach to enhance tumor targeting and achieve targeted delivery of camptothecin (CPT) based on a tumor-homing internalizing RGD peptide (iRGD). We synthesized an iRGD-camptothecin conjugate (iRGD-CPT) covalently coupled by a heterobifunctional linker and evaluated its in vitro and in vivo activity in human colon cancer cells. In vitro studies revealed that iRGD-CPT penetrated cells efficiently and reduced colon cancer cell viability to a significantly greater extent at micromolar concentrations than did the parent drug. Furthermore, iRGD-CPT showed high distribution toward tumor tissue, effectively suppressed tumor progression, and showed enhanced antitumor effects relative to the parent drug in a mouse model, demonstrating that iRGD-CPT is effective in vivo cancer treatment. These results suggest that intracellular delivery of CPT via the iRGD peptide is a promising drug delivery strategy that will facilitate the development of CPT derivatives and prodrugs with improved efficacy.

Mitochondria targeting molecular transporters: synthesis, lipophilic effect, and ionic complex.

As mitochondria are potential therapeutic targeting sites for the treatment of human diseases, delivering cytotoxic drugs, antioxidants, and imaging molecules to mitochondria can provide new therapeutic opportunities. In an attempt to develop a new mitochondria-targeting vector, we synthesized sorbitol-based molecular transporters with multiple guanidines, measured their partition coefficients, compared their targeting efficiency using fluorescent images and Pearson's correlation coefficients, and studied cellular uptake mechanisms. To increase the targeting ability of these molecular transporters to mitochondria, alanine-naphthalene as a lipophilic group was attached to the molecular transporter, which improved translocation across cellular membranes and led to higher accumulation in mitochondria. The molecular transporter was able to form an ionic complex with antibiotics, resulting in low cell viability. These data demonstrate that the molecular transporter with a lipophilic group could be utilized as a potential drug delivery vector for treating mitochondrial dysfunction.

Highly stretchable superhydrophobic surface by silica nanoparticle embedded electrospun fibrous mat.

HYPOTHESIS: Obtaining simultaneous stretchability and superhydrophobicity remains a great challenge in stretchable electronics, and wearable devices. Inspired by natural surfaces, such as lotus leaf, surface roughness and coating materials are the fundamental requirements to achieve superhydrophobicity. EXPERIMENTS: We prepared an elastic fibrous mat by electrospinning of a composite solution made of thermoplastic elastomer as an organic polymer matrix, and silica nanoparticles as inorganic additives to support surface roughness. To enhance hydrophobicity, the pristine mat was immersed into a solution of fluorinated material, which can decrease the surface energy. FINDINGS: The pristine fibrous mat showed high stretchability (with more than 1000% strain), and superhydrophobicity (with a contact angle of 156°, and a sliding angle of 7.8°). Superhydrophobicity did not disappear when the fibrous mat was stretched up to 1000%. Sliding angles were less than 10° under different strain levels only in longitudinal direction, suggesting the stretchable superhydrophobic surface is effective in rolling off the water droplet in one direction. The fibrous mat was repeatedly stretched 1000 times to 1000% strain; the material showed stable stretchability and superhydrophobicity. Based on these observations, the resulting fibrous mat appears to be in the Cassie-Baxter wetting state.

Versatility of cell-penetrating peptides for intracellular delivery of siRNA.

The plasma membrane is a large barrier to systemic drug delivery into cells, and it limits the efficacy of drug cargo. This issue has been overcome using cell-penetrating peptides (CPPs). CPPs are short peptides (6-30 amino acid residues) that are potentially capable of intracellular penetration to deliver drug molecules. CPPs broadened biomedical applications and provide a means to deliver a range of biologically active molecules, such as small molecules, proteins, imaging agents, and pharmaceutical nanocarriers, across the plasma membrane with high efficacy and low toxicity. This review is focused on the versatility of CPPs and advanced approaches for siRNA delivery.