The search for new pharmaceuticals that are specific for diseased rather than normal cells in the case of cancer and viral disease has raised interest in locally acting drugs that act over short distances within the cell and for which different cell compartments have distinct sensitivities. Thus, photosensitizers (PSs) used in anti-cancer therapy should ideally be transported to the most sensitive subcellular compartments in order for their action to be most pronounced. Here we describe the design, production, and characterization of the effects of bacterially expressed modular recombinant transporters for PSs comprising 1) alpha-melanocyte-stimulating hormone as an internalizable, cell-specific ligand; 2) an optimized nuclear localization sequence of the SV40 large T-antigen; 3) an Escherichia coli hemoglobin-like protein as a carrier; and 4) an endosomolytic amphipathic polypeptide, the translocation domain of diphtheria toxin. These modular transporters delivered PSs into the nuclei, the most vulnerable sites for the action of PSs, of murine melanoma cells, but not non-MSH receptor-overexpressing cells, to result in cytotoxic effects several orders of magnitude greater than those of nonmodified PSs. The modular fusion proteins described here for the first time, capable of cell-specific targeting to particular subcellular compartments to increase drug efficacy, represent new pharmaceuticals with general application.

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The rapid growth of drug-resistant bacteria all over the world has given rise to a major research challenge, namely a search for alternative treatments to which bacteria will be unable to develop resistance. Photodynamic therapy is an approach of this kind. It involves the use of photosensitizers in combination with visible light at a certain wavelength to excite the former and generate reactive oxygen species. Various synthetic heterocyclic compounds are used as photosensitizers. Of these, derivatives of natural chlorophylls have a special place due to their properties. This review deals with the use of such compounds in antimicrobial PDT.

Theranostic upconversion nanoparticles (UCNPs) are ideal candidates for personalized medicine. We present a smart, easy-to-prepare nanohybrid (NH) suitable for NIR-theragnosis and imaging tracking without triggering therapy simultaneously. The photophysical features of each component have been carefully selected in order to maximize the capabilities for theragnosis, in particular, the upconversion emission and the photosensitizer absorption. In addition, NH presents a fluorescent marker with one-photon absorption in the green and two-photon absorption cross-section at NIR wavelengths where the UCNP does not absorb, thus enabling innocuous tracking. Thus, the NH consists of NaYF4:Yb, Er, Tm (UCYbErTm) emitting in the UV, vis, and NIR; a broadband-absorbing natural porphyrin (PP) in the UV-to-NIR range but from 580 to 675 nm; and a 1,8-naphthalimide (NI) with two absorption bands (UV, VIS), and dual emission. In vitro assays demonstrate that UCYbErTm@PP/NI NH is noncytotoxic and extremely effective for NIR-induced cancer cell death. Moreover, this NH offers fluorescence tracking features without therapy due to the specific excitation of NI in the NIR and emission in the orange. This strategy opens up new alternatives for successful and noninvasive antitumoral theragnosis.

Upon interaction of hydrazine hydrate with bacteriopurpurin, the initially formed monohydrazide in an acidic medium readily reacts with the second carboxyl group to give a six-membered N-aminocycloimide of bacteriochlorin p6. The free amino group at the fused imide ring makes it easy to obtain N-alkyl and N-acyl derivatives. The compounds thus obtained exhibit high light-induced cytotoxicity on A549 human adenocarcinoma cells.