Porphyrins are tetrapyrrolic structures that have been extensively studied in the recent years, especially for their applicability in the field of theranostic nanomedicine. Selectivity for tumor tissues manifested by the porphyrins, as well as usage of visible radiations for their activation implying lower energies compared to those utilized in radiotherapy, are aspects that recommend photodynamic therapy with porphyrins as efficient alternative treatment to chemotherapy and radiotherapy, with good potential in management of different types of cancer. One of the advantages of simultaneous use of porphyrins in therapeutic and diagnosis purpose, is the fact that, once internalized in the tumor cell, PS becomes an important indicator in monitoring antitumor treatment, the fluorescence signal decreasing with the damage tumor cells. The interaction studies with cell membrane can be very useful in highlight of some strategies for designing and optimizing the potential of cellular internalization of novel theranostic agents. The aim of the present study was to assess effects exerted in vitro by three unsymmetrical porphyrins (P, Zn(II)P and Cu(II)P), on membrane anisotropy and transmembrane potential of U937 cell lines, using DiBAC4(3) and TMA-DPH as fluorescence probe. The results suggest the hyperpolarizing effect of the free base porphyrin (0.5μM, 5μM, 50μM) on the cell membrane, which recommends its use for therapeutic purposes in low concentrations. The investigated metalloporphyrins have a reduced effect on the membrane potential at 5μM doses, with an increase of 15% hyperpolarization for 0.5µM and 50µM concentrations, suggesting a dose-dependent mechanism of action.