SummaryPhotodynamic therapy (PDT) has developed over last century and is now becoming a more widely used medical tool having gained regulatory approval for the treatment of various diseases such as cancer and macular degeneration. It is a two-step technique in which delivery of a photosensitizing drug is followed by irradiation of light. Activated photosensitizers transfer energy to molecular oxygen which results in generation of reactive oxygen species which in turn cause cells apoptosis or necrosis. Although this modality has significantly improved quality of life and survival time for many cancer patients it still offers significant potential for further improvement. In addition to the development of new PDT drugs, the use of nanosized carriers for photosensitizers is a promising approach which might improve the efficiency of photodynamic activity and which can overcome many side effects associated with classic photodynamic therapy. This review aims at highlighting the different types of nanomedical approaches currently used in PDT and outlines future trends and limitations of nanodelivery of photosensitizers. PDT -photodynamic therapy; PGA -poly(glycolic acid); PGLA -poly(D,L-lactide-coglycolide); PLA -poly(lactic acid); PS -photosensitizer; PEG -polyethylene glycol; ALA  aminolevulinic acid; m-THPC  5,10,15,20-tetra-(m-hydroxyphenyl)chlorine; m-THPP  meso-tetra(p-hydroxyphenyl); PpIX  protoporphyrin; Hp  hematoporphyrin; Pc4  silicon phthalocyanine; Ig  immunoglobulin; Tf  transferrin; TfR  transferrin receptor; VEGF  vascular endothelial growth factor; EPR  enhanced permeability and retention effect; FRET  fluorescence resonance energy transfer; MRI  magnetic resonance imaging; RES  reticuloendothelial system; ROS  reactive oxygen species; NP  nanoparticle; ND -nanodiamonds; SNP  silica nanoparticle; AMD  age-related macular degeneration; CNV  choroidal neovascularization; PTT  photothermal therapy;

The receptor for advanced glycation endproducts (RAGE) is expressed under pathological conditions in many tissues and has been assigned many functions. We demonstrate, in normal human lung tissue, the preferential and highly abundant expression of RAGE by quantitative polymerase chain reaction. In addition, RAGE expression, as a specific differentiation marker of alveolar epithelial type I cells (AT I cells), and its localization to the basolateral plasma membrane have been confirmed by means of newly raised monoclonal antibodies. The physiological function of RAGE on AT I cells has previously remained elusive. By using HEK293 cells transfected with cDNA encoding for full-length RAGE, we show that RAGE enhances the adherence of epithelial cells to collagen-coated surfaces and has a striking capacity for inducing cell spreading. The preferential binding of RAGE to collagen has been confirmed by assaying the binding of soluble RAGE to various substrates. RAGE might thus assist AT I cells to acquire a spreading morphology, thereby ensuring effective gas exchange and alveolar stability.

Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs. Depot-type release systems are available to achieve sustained release of drugs over time. Conjugation to synthetic or biological polymers affords long circulating formulations. Administration of biological drugs through non-parenteral routes shows excellent performance and the first products have reached the market. This Review presents the main accomplishments in this field and illustrates the materials and methods behind existing and upcoming successful formulations and delivery strategies for biological drugs.

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.