BackgroundTamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response.ResultsHere we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV365 nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells.ConclusionsThis work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0345-2) contains supplementary material, which is available to authorized users.

BackgroundPhotodynamic therapy is a promising cancer therapy modality but its application for deep-seated tumor is mainly hindered by the shallow penetration of visible light. X-ray-mediated photodynamic therapy (PDT) has gained a major attention owing to the limitless penetration of X-rays. However, substantial outcomes have still not been achieved due to the low luminescence efficiency of scintillating nanoparticles and weak energy transfer to the photosensitizer. The present work describes the development of Y2.99Pr0.01Al5O12-based (YP) mesoporous silica coated nanoparticles, multifunctionalized with protoporphyrin IX (PpIX) and folic acid (YPMS@PpIX@FA) for potential application in targeted deep PDT.ResultsA YP nanophosphor core was synthesized using the sol–gel method to be used as X-ray energy transducer and was then covered with a mesoporous silica layer. The luminescence analysis indicated a good spectral overlap between the PpIX and nanoscintillator at the Soret as well as Q-band region. The comparison of the emission spectra with or without PpIX showed signs of energy transfer, a prerequisite for deep PDT. In vitro studies showed the preferential uptake of the nanocomposite in cancer cells expressing the folate receptorFolr1, validating the targeting efficiency. Direct activation of conjugated PpIX with UVA in vitro induced ROS production causing breast and prostate cancer cell death indicating that the PpIX retained its activity after conjugation to the nanocomposite. The in vivo toxicity analysis showed the good biocompatibility and non-immunogenic response of YPMS@PpIX@FA.ConclusionOur results indicate that YPMS@PpIX@FA nanocomposites are promising candidates for X-ray-mediated PDT of deep-seated tumors. The design of these nanoparticles allows the functionalization with exchangeable targeting ligands thus offering versatility, in order to target various cancer cells, expressing different molecular targets on their surface.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0344-3) contains supplementary material, which is available to authorized users.

ations in cascade reactions on nanoassemblies are of great importance. Thus, in this work, important parameters of enzyme kinetics in cascade reaction and the molecular tools for the design and optimization of bi-and multi-enzymatic nanobioreactors reactions are discussed.

Nanohybrid systems combining both persistent luminescence and magnetic property are recent breakthroughs in novel multimodal imaging and cancer therapy; however, integrating strategies at a common platform is complex. Herein, we report the synthesis of a Gd3Al5−xGaxO12:Ce3+,Pr3+ (GAGG:Ce,Pr) nanophosphor (x = 1–5) with simultaneous paramagnetic/persistence luminescence via a simple tartaric acid assisted solgel synthesis. Structural analysis revealed the formation of a pure cubic garnet crystal of GAGG:Ce,Pr, which expanded linearly upon gallium incorporation. Moreover, the novel paramagnetic/persistence luminescent material showed the formation of nanoparticles with excellent colloidal stability. Photoluminescence emission analysis showed a broad emission band in the range of λ = 500–750 nm attributed to (5d → 4f) transitions of Ce3+ and a sharp peak centered at λ = 612 nm attributed to electronic transitions (1D2 → 3H4) within Pr3+ upon blue light excitation. In particular, GAGG:Ce-Pr sample with Al:Ga ratio 1:4 yielded persistent luminescence upon blue, UV, and white light excitation at room temperature. Additionally, GAGG:Ce-Pr (x = 4) nanophosphor was paramagnetic and also showed signs of weak ferromagnetism at ambient temperature. Cellular toxicity analysis in different cell lines revealed the relatively safe nature of nanoparticles at the tested concentrations. Overall, in our preliminary analysis, GAGG:Ce-Pr (x = 4) showed the persistent optomagnetic property and low cellular toxicity for potential utilization in multimodal theranostic applications.