It was established through in vivo T₁ measurements at low magnetic fields that tumour cells display proton T₁ values that are markedly longer than those shown by healthy tissue. Moreover, it has been found that the elongation of T₁ parallels the aggressiveness of the investigated tumour. The T₁ lengthening is associated with an enhanced water exchange rate across the transcytolemmal membrane through an overexpression/upregulation of GLUT1 and Na⁺/K⁺ ATPase transporters. It follows that the intracellular water lifetime represents a hallmark of tumour cells that can be easily monitored by measuring T₁ at different magnetic field strengths ranging from 0.2 to 200 mT.

Polylactic and glycolic acid nanoparticles (PLGA-NPs), coated with L-ferritin, are exploited for the simultaneous delivery of paclitaxel and an amphiphilic Gd based MRI contrast agent into breast cancer cells (MCF7). L-ferritin has been covalently conjugated to the external surface of PLGA-NPs exploiting NHS activated carboxylic groups. The results confirmed that nanoparticles decorated with L-ferritin have many advantages with respect to both albumin-decorated and nondecorated particles. Ferritin moieties endow PLGA-NPs with targeting capability, exploiting SCARA5 receptors overexpressed by these tumor cells, that results in an increased paclitaxel cytotoxicity. Moreover, protein coating increased nanoparticle stability, thus reducing the fast and aspecific drug release before reaching the target. The theranostic potential of the nanoparticles has been demonstrated by evaluating the signal intensity enhancement on T₁-weighted MRI images of labeled MCF7 cells. The results were compared with that obtained with MDA cells used as negative control due to their lower SCARA5 expression.

The heating efficiency of an assembly of Mn-doped magnetite nanoparticles can be tuned so as to depend linearly on the non-superparamagnetic fraction.

Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar ¹ H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger-sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe-NPs in PLGA-NPs also made it possible to maintain Néel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15–20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe-NPs designed for MFH applications.

Cyclic adenosine 3′,5′-monophosphate (cAMP)–elevating agents, such as β ₂ -adrenergic receptor (β ₂ -AR) agonists and phosphodiesterase (PDE) inhibitors, remain a mainstay in the treatment of obstructive respiratory diseases, conditions characterized by airway constriction, inflammation, and mucus hypersecretion. However, their clinical use is limited by unwanted side effects because of unrestricted cAMP elevation in the airways and in distant organs. Here, we identified the A-kinase anchoring protein phosphoinositide 3-kinase γ (PI3Kγ) as a critical regulator of a discrete cAMP signaling microdomain activated by β ₂ -ARs in airway structural and inflammatory cells. Displacement of the PI3Kγ-anchored pool of protein kinase A (PKA) by an inhaled, cell-permeable, PI3Kγ mimetic peptide (PI3Kγ MP) inhibited a pool of subcortical PDE4B and PDE4D and safely increased cAMP in the lungs, leading to airway smooth muscle relaxation and reduced neutrophil infiltration in a murine model of asthma. In human bronchial epithelial cells, PI3Kγ MP induced unexpected cAMP and PKA elevations restricted to the vicinity of the cystic fibrosis transmembrane conductance regulator (CFTR), the ion channel controlling mucus hydration that is mutated in cystic fibrosis (CF). PI3Kγ MP promoted the phosphorylation of wild-type CFTR on serine-737, triggering channel gating, and rescued the function of F508del-CFTR, the most prevalent CF mutant, by enhancing the effects of existing CFTR modulators. These results unveil PI3Kγ as the regulator of a β ₂ -AR/cAMP microdomain central to smooth muscle contraction, immune cell activation, and epithelial fluid secretion in the airways, suggesting the use of a PI3Kγ MP for compartment-restricted, therapeutic cAMP elevation in chronic obstructive respiratory diseases.