Tamoxifen 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. Here 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. This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.

Photodynamic 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. A 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. Our 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.

In an attempt to explore use of PET radioisotope, ⁶⁸Ga, in the diagnosis of Alzheimer's disease, a metal-based homodimeric ligand exhibiting high affinity towards Aβ aggregates was designed by conjugating two chalcone units with the chelating system, diethylenetriaminepentaacetic acid. Bischalcone derivative, 5,8-bis(carboxymethyl)-13-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)-2-(2-(2-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)ethylamino)-2-oxoethyl)-10-oxo-2,5,8,11-tetraazatridecane-1-carboxylic acid, DT(Ch)₂ was synthesized in 95% yield with high purity. It was radiolabelled with ⁶⁸Ga under mild conditions with 85.4% efficiency and 9.5–10 MBq nmol⁻¹ specific activity. An in vitro binding assay on Aβ42 aggregates displayed high binding affinity of ⁶⁸Ga-DT(Ch)₂ and inhibition constant of 4.18 ± 0.62 nM. The fluorescent properties of the ligand with peaks of absorption/emission at 410/540 nm exhibited a blue shift with 5.5-fold increase in emission intensity on binding with Aβ aggregates. Blood kinetics of the complex performed on normal rabbit exhibited fast clearance (t_1/2(F) = 24 ± 0.08 min; t_1/2(S) = 2 h 40 ± 0.04 min). Ex vivo biodistribution analysis demonstrated blood–brain barrier penetration with brain uptake of 1.24 ± 0.31% ID g⁻¹ at 2 min p.i. and rapid washout with negligible activity (0.36% ID g⁻¹) left at 30 min p.i. These preliminary studies reveal that the bivalent approach of synthesis had minimal effect on binding affinity, signifying that the developed ⁶⁸Ga-complex, ⁶⁸Ga-DT(Ch)₂, may offer a new perspective in generator produced PET imaging probes for Alzheimer's disease.

• Biocompatible carbon dots (CDs) and nanohydroxyapatite (nHA) have attracted much attention for the development of optical imaging probes. • This review discusses the development of CD and nHA based nanomaterials as multifunctional agents for cancer theranostics. • The effect of synthesis strategies and doping on photoluminescent properties along with tuning of emission in biological window has been briefly reviewed. • The cancer targeting strategies, biocompatibility and biodistribution of CDs and nHA based luminescent probes is discussed. • A summary of current challenges and future perspectives is provided.