Evaluation of the correlation between porphyrin accumulation in cancer cells and functional positions for application as a drug carrier

Porphyrin derivatives accumulate selectively in cancer cells and are can be used as carriers of drugs. Until now, the substituents that bind to porphyrins (mainly at the meso-position) have been actively investigated, but the effect of the functional porphyrin positions (β-, meso-position) on tumor accumulation has not been investigated. Therefore, we investigated the correlation between the functional position of substituents and the accumulation of porphyrins in cancer cells using cancer cells. We found that the meso-derivative showed higher accumulation in cancer cells than the β-derivative, and porphyrins with less bulky substituent actively accumulate in cancer cells. When evaluating the intracellular distribution of porphyrin, we found that porphyrin was internalized by endocytosis and direct membrane permeation. As factors involved in these two permeation mechanisms, we evaluated the affinity between porphyrin-protein (endocytosis) and the permeability to the phospholipid bilayer membrane (direct membrane permeation). We found that the binding position of porphyrin affects the factors involved in the transmembrane permeation mechanisms and impacts the accumulation in cancer cells.

mTHPC-Loaded Extracellular Vesicles Significantly Improve mTHPC Diffusion and Photodynamic Activity in Preclinical Models

Extracellular vesicles (EVs), derived from the cell, display a phospholipid bilayer membrane that protects the cargo molecules from degradation and contributes to increasing their stability in the bloodstream and tumor targeting. EVs are interesting in regard to the delivery of photosensitizers (PSs) used in the photodynamic therapy (PDT), as they allow us to overcome the limitations observed with liposomes. In fact, liposomal formulation of meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foslip®), one of the most potent clinically approved PSs, is rapidly destroyed in circulation, thus decreasing in vivo PDT efficacy. mTHPC-EV uptake was evaluated in vitro in a 3D human colon HT-29 microtumor and in vivo study was performed in HT-29 xenografted mice. The obtained data were compared with Foslip®. After intravenous injection of the mTHPC formulations, biodistribution, pharmacokinetics and PDT-induced tumor regrowth were evaluated. In a 3D model of cells, mTHPC-EV uptake featured a deeper penetration after 24h incubation compared to liposomal mTHPC. In vivo results showed a considerable improvement of 33% tumor cure with PDT treatment applied 24h after injection, while 0% was observed after Foslip®/PDT. Moreover, 47 days were required to obtain ten times the initial tumor volume after mTHPC-EVs/PDT compared to 30 days for liposomal mTHPC. In conclusion, compared to Foslip®, mTHPC-EVs improved mTHPC biodistribution and PDT efficacy in vivo. We deduced that a major determinant factor for the improved in vivo PDT efficacy is the deep mTHPC intratumor penetration.

Applications of Magnetotactic Bacteria, Magnetosomes and Magnetosome Crystals in Biotechnology and Nanotechnology: Mini-Review

Magnetotactic bacteria (MTB) biomineralize magnetosomes, which are defined as intracellular nanocrystals of the magnetic minerals magnetite (Fe3O4) or greigite (Fe3S4) enveloped by a phospholipid bilayer membrane. The synthesis of magnetosomes is controlled by a specific set of genes that encode proteins, some of which are exclusively found in the magnetosome membrane in the cell. Over the past several decades, interest in nanoscale technology (nanotechnology) and biotechnology has increased significantly due to the development and establishment of new commercial, medical and scientific processes and applications that utilize nanomaterials, some of which are biologically derived. One excellent example of a biological nanomaterial that is showing great promise for use in a large number of commercial and medical applications are bacterial magnetite magnetosomes. Unlike chemically-synthesized magnetite nanoparticles, magnetosome magnetite crystals are stable single-magnetic domains and are thus permanently magnetic at ambient temperature, are of high chemical purity, and display a narrow size range and consistent crystal morphology. These physical/chemical features are important in their use in biotechnological and other applications. Applications utilizing magnetite-producing MTB, magnetite magnetosomes and/or magnetosome magnetite crystals include and/or involve bioremediation, cell separation, DNA/antigen recovery or detection, drug delivery, enzyme immobilization, magnetic hyperthermia and contrast enhancement of magnetic resonance imaging. Metric analysis using Scopus and Web of Science databases from 2003 to 2018 showed that applied research involving magnetite from MTB in some form has been focused mainly in biomedical applications, particularly in magnetic hyperthermia and drug delivery.

Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics

Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles can transport bioactive molecules containing mRNAs, proteins, DNA fragments, and non-coding RNAs from a donor cell to recipient cells, and cause the alteration in genetic and epigenetic factors and reprogramming of the target cells. Many diverse cell types such as mesenchymal cells, immune cells, and cancer cells can induce the release of exosomes. Increasing evidence illustrated that the exosomes derived from tumor cells might trigger the tumor initiation, tumor cell growth and progression, metastasis, and drug resistance. The secreted nanovesicles of exosomes can play significant roles in cells communicate via shuttling the nucleic acid molecules and proteins to target cells and tissues. In this review, we discussed multiple mechanisms related to biogenesis, load, and shuttle of the exosomes. Also, we illustrated the diverse roles of exosomes in several types of human cancer development, tumor immunology, angiogenesis, and metastasis. The exosomes may act as the promising biomarkers for the prognosis of various types of cancers which suggested a new pathway for anti-tumor therapeutic of these nanovesicles and promoted exosome-based cancer for clinical diagnostic and remedial procedures.

Thermally-induced lateral assembly of a PEG-containing amphiphile triggering vesicle budding

A macrocyclic amphiphile consisting of an octaethylene glycol chain with aromatic and aliphatic hydrophobic units undergoes lateral self-assembly in an Ld-state phospholipid bilayer membrane upon heating, followed by vesicle budding.

Colloidal Apatite Nanoparticles: Insights on their Interaction with Cells and Artificial Lipid Membranes

Biomimetic nanocrystalline apatites are analogous to bone mineral. They can be exploited not only for bone regeneration applications, but it is also possible to take advantage of their biomimetic features to explore novel domains of research such as in nanomedicine, if the nanoparticles are stabilized as a colloidal formulation. In this contribution, we concentrate on AEP/HMP-stabilized colloidal apatite nanoparticles (NPs) and on their interaction with different types of cells so as to get experimental evidence on their low cytotoxicity, non-proinflammatory potential, and good compatibility with Red Blood Cells. We then started to explore their interaction with an artificial free-standing phospholipid bilayer, as a simplified model for cell membranes: results indicate, for the first time, that these colloidal apatite NPs can modulate phospholipid bilayer membrane properties, and may even favor the permeation of small molecules (illustrated here with luminescent FITC), which could ultimately be exploited for nanomedicine applications in view of enhancing intracellular drug delivery.

Design of artificial membrane transporters from gold nanoparticles with controllable hydrophobicity

Gold nanoparticles with variable hydrophobicity have been prepared in three different size regimes following established methods. The control of hydrophobicity was achieved by complexation of the 18-crown-6-CH2-thiolate ligand shell with potassium ions. Potassium dependent phase transfer of these particles from dispersion in water to chloroform was demonstrated, and the equilibrium partitioning of the particles in water–chloroform liquid/liquid systems was quantified by optical spectroscopy. The gradual complexation of the ligand shell with potassium ions was further monitored by zeta potential measurements. Potassium dependent insertion of nanoparticles into the phospholipid bilayer membrane of vesicles in aqueous dispersion has been demonstrated by cryogenic transmission electron microscopy (cryo-TEM). Nanoparticle-dependent potassium ion transport across the vesicle membrane has been established by monitoring the membrane potential with fluorescence spectroscopy using a potential sensitive dye.