The synthesis, photophysical characterization, and modeling of a new library of halogen-free photosensitizers (PS) based on orthogonal boron dipyrromethene (BODIPY) dimers are reported. Herein we establish key structural factors in order to enhance singlet oxygen generation by judiciously choosing the substitution patterns according to key electronic effects and synthetic accessibility factors. The photosensitization mechanism of orthogonal BODIPY dimers is demonstrated to be strongly related to their intrinsic intramolecular charge transfer (ICT) character through the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) mechanism. Thus, singlet oxygen generation can be effectively modulated through the solvent polarity and the presence of electron-donating or withdrawing groups in one of the BODIPY units. The photodynamic therapy (PDT) activity is demonstrated by in vitro experiments, showing that selected photosensitizers are efficiently internalized into HeLa cells, exhibiting low dark toxicity and high phototoxicity, even at low PS concentration (0.05-5×10 m).

Promising advances in nanomedicine such as magnetic hyperthermia rely on a precise control of the nanoparticle performance in the cellular environment. This constitutes a huge research challenge due to difficulties for achieving a remote control within the human body. Here we report on the significant double role of the shape of ellipsoidal magnetic nanoparticles (nanorods) subjected to an external AC magnetic field: first, the heat release is increased due to the additional shape anisotropy; second, the rods dynamically reorientate in the orthogonal direction to the AC field direction. Importantly, the heating performance and the directional orientation occur in synergy and can be easily controlled by changing the AC field treatment duration, thus opening the pathway to combined hyperthermic/mechanical nanoactuators for biomedicine. Preliminary studies demonstrate the high accumulation of nanorods into HeLa cells whereas viability analysis supports their low toxicity and the absence of apoptotic or necrotic cell death after 24 or 48 h of incubation.

The cationic porphyrin meso-tetra(4-[Formula: see text]-methylpyridyl)porphine (TMPyP) has a high yield of singlet oxygen generation upon light activation and a strong affinity for DNA. These advantageous properties have turned it into a promising photosensitizer for use in photodynamic therapy (PDT). In this review, we have summarized the current state-of-the-art applications of TMPyP for the treatment of cancer as well as its implementation in antimicrobial PDT. The most relevant studies reporting its pharmacokinetics, subcellular localization, mechanism of action, tissue biodistribution and dosimetry are discussed. Combination strategies using TMPyP-PDT together with other photosensitizers and chemotherapeutic agents to achieve synergistic anti-tumor effects and reduce resistance to therapy are also explored. Finally, we have addressed emerging applications of this porphyrin, including nanoparticle-mediated delivery, controlled drug release, biosensing and G-quadruplex stabilization for tumor growth inhibition. Altogether, this work highlights the great potential and versatility that TMPyP can offer in different fields of biomedicine such us cancer treatment or antimicrobial therapy.

We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NP) with negative, positive and hydrophobic surfaces that were incorporated outside, inside or between the lipid bilayers, respectively. To characterize how NP are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NP are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 ºC with high enthalpy 34.8 J/g) avoiding the leakage of encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100 % of cellular uptake was achieved with a high cell survival (above 80 %), which is preserved (83 %) for doxorubicin loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 hour, leading to a cell survival reduction of 20 %. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating avoiding drug degradation. In conclusion, these drug loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place efficiently using an external AMF reducing or even eliminating side effects.

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Biscyclometalated Ir complexes involving boron-dipyrromethene (BODIPY)-based ancillary ligands, where the BODIPY unit is grafted to different chelating cores (acetylacetonate for Ir-1 and Ir-2, and bipyridine for Ir-3) by the BODIPY meso position, have been synthesized and characterized. Complexes with the BODIPY moiety directly grafted to acetylacetonate (Ir-1 and Ir-2) exhibit higher absorption coefficients (ϵ≈4.46×10 m cm and 3.38×10 m cm at 517 nm and 594 nm, respectively), higher moderate fluorescence emission (φ ≈0.08 and 0.22 at 528 nm and 652 nm, respectively) and, in particular, more efficient singlet oxygen generation upon visible-light irradiation (φ ≈0.86 and 0.59, respectively) than that exhibited by Ir-3 (φ ≈0.51, but only under UV light). Phosphorescence emission, nanosecond time-resolved transient absorption, and DFT calculations suggest that BODIPY-localized long-lived IL states are populated for Ir-1 and Ir-2. In vitro photodynamic therapy (PDT) activity studied for Ir-1 and Ir-2 in HeLa cells shows that such complexes are efficiently internalized into the cells, exhibiting low dark- and high photocytoxicity, even at significantly low complex concentration, making them potentially suitable as theranostic agents.

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Bright BODIPY photosensitizers reveal LDs as valuable targets for PDT.