Transdermal Penetrating Peptide Conjugated Liposomes as Drug Delivery Carrier Comprising Macromolecules

: The aim of the study was to investigate a system using liposomes and cell penetrating peptides (CPP) for optimal transdermal delivery of macromolecules. Typical DOPE liposomes were prepared with lipid mixture (DOPE:PC:Chol = 1.5:1.5:2.0, molar ratio) and active materials (Rhodamine B; MW ~480 and Dextran-RITC; MW ~10,000). CPP-conjugated DOPE liposomescontaining active materials were prepared by conjugating the peptide to DOPE liposomes (DOPE:PC:Chol:DSPE-PEG-Mal = 1.5:1.1:2.0:0.2 or 0.4, molar ratio). Physical properties of both liposomes were evaluated, including particle size and zeta potential. The particle sizes of typical liposome and CPP-DOPE liposome were approximately 100 nm, and the zeta potential values of both liposomes were approximately -25mV and over +11mV respectively. Moreover, cellular uptake efficiency was assessed by flow cytometry (FACS). CPP-conjugated liposomes resulted higher cellular uptake efficiency compared to typical DOPE liposomes, showing higher fluorescent intensity in CPP-DOPE liposomes. In confocal laser scanning microscope (CLSM) studies, both cellular uptake and skin permeation were visually estimated. In the case of Rhodamine B, having a relatively small molecular weight,absorption into the cell was successful, and showed the highest rate of cellular uptake with CPP-DOPE liposomes. Dextran-RITC, a macromolecule with a relatively bigger molecular weight, showed similar results to Rhodamine B. In terms of skin permeation, CPP-DOPE liposomes containing Rhodamine B showed noticeable skin absorption after 4 and 18 hours, and the permeation range was wider and thicker than that with typical liposomes. For Dextran-RITC, with typical DOPE liposome, it was hardly permeable through the skin, but with CPP-DOPE liposomes, on the other hand, the skin permeations after 4 and 18 hours were remarkable. The improved cellular uptake and skin permeation of the CPP-conjugated liposomes are due to the cationic arginine-rich peptide. In vivo studies also proved that the CPP-conjugated liposomes are superior in depigmentation and anti-wrinkle studies than typical liposomes. These results demonstrate that the CPP-conjugated liposomes could also be effective for transdermal drug delivery of antioxidant and anti-aging therapeutics.

Why synthetic virus-like nanoparticles can achieve higher cellular uptake efficiency?

The disruption effect of spikes leads to the superior penetrability of virus-like nanoparticles during the translocation process.

Polydopamine-doped virus-like structured nanoparticles for photoacoustic imaging guided synergistic chemo-/photothermal therapy

The therapeutic diagnosis effect of cancer commonly depends on the cellular uptake efficiency of nanomaterials.

Facile Synthesis of Triangular and Hexagonal Anionic Gold Nanoparticles and Evaluation of Their Cytotoxicity

Comprehension of the shape-dependent properties of gold nanoparticles (AuNPs) could benefit the advancements in cellular uptake efficiency. Spherical AuNPs have generally been used for drug delivery, and recent research has indicated that the cellular uptake of triangular AuNPs was higher than that of spherical ones. Previous reports have also revealed that chemically synthesized AuNPs were cytotoxic. Therefore, we have developed a facile, cost-effective, and environmentally friendly method for synthesizing triangular and hexagonal anionic AuNPs. The zeta potential of the synthesized AuNPs was negative, which indicated that their surface could be easily functionalized with positively charged molecules to upload drugs or biomolecules. Transmission electron microscopy (TEM) images illustrated that the largest particle size of the synthesized quasi-hexagonal AuNPs was 61 nm. The TEM images also illustrated that two types of equilateral-triangular AuNPs were synthesized: One featured sharp and the other rounded corners. The sides of the smallest and largest triangular AuNPs were 23 and 178 nm, respectively. Energy-dispersive X-ray spectra of the green-synthesized AuNPs indicated that they consisted entirely of elemental Au. The cytotoxicity of the green-synthesized AuNPs was evaluated using 3T3-L1 adipocytes. Using cell viability data, we determined that the green-synthesized AuNPs did not exhibit any cytotoxic effects on 3T3-L1 adipocytes.

Biocompatibility Profile and In Vitro Cellular Uptake of Self-assembled Alginate Nanoparticles

Polymeric nanoparticles could offer promising controlled drug delivery. The biocompatibility is of extreme importance for future applications in humans. Self-assembled polymeric nanoparticles based on phenylalanine ethyl ester (PAE)-modified alginate (Alg) had been successfully prepared and characterized in our lab. However, little is known about their interaction with cells and other biological systems. In this study, nanoparticles (NPs) based on PAE-Alg conjugates (PEA-NPs) with different degree of substitution (DS) were prepared and investigated. Our results showed that PEA-NPs had no effects on the proliferation of the human intestinal epithelial Caco-2 cells at concentrations up to 1000 μg/mL. Furthermore, the in vitro cellular uptake profile of PEA-NPs, concerning several parameters involved in the application of therapeutic or diagnostic NPs, such as NPs concentration, time and temperature, was described. Different NPs have been adopted for cellular uptake studies and the NPs internalized into Caco-2 cells were quantified. Cellular uptake efficiency could reach 60% within 4 h. PEA-NPs also showed greater cell permeability than oleoyl alginate ester nanoparticles (OAE-NPs) previously prepared in our lab. Our studies reveal that NPs based on PEA conjugate are promising nanosystems for cellular delivery.

Biocompatible carbon-doped MoSe2 nanoparticles as a highly efficient targeted agent for human renal cell carcinoma

HK-2 cells have weak cellular uptake efficiency leading to high viability with carbon-doped MoSe2 nanoparticles.

Shaping Rolling Circle Amplification Products into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Application to In Vitro and In Vivo Delivery of a Photosensitizer

Rolling circle amplification (RCA) is a robust way to generate DNA constructs, which are promising materials for biomedical applications including drug delivery because of their high biocompatibility. To be employed as a drug delivery platform, however, the DNA materials produced by RCA need to be shaped into nanoparticles that display both high cellular uptake efficiency and nuclease resistance. Here, we showed that the DNA nanoparticles (DNPs) can be prepared with RCA and modified nucleotides that have side-chains appended on the nucleobase are capable of interacting with the DNA strands of the resulting RCA products. The incorporation of the modified nucleotides improved cellular uptake efficiency and nuclease resistance of the DNPs. We also demonstrated that these DNPs could be employed as carriers for the delivery of a photosensitizer into cancer cells to achieve photodynamic therapy upon irradiation at both the in vitro and in vivo levels.