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Naturally-derived metallo-bacteriochlorophylls have attracted much attention since their clinical approval for cancer photodynamic therapy. Their therapeutic properties are rooted in the metal complexation of bacteriochlorophylls, which endows them with optical properties favourable for biophotonic and biomedical applications, including near-infrared light-activated reactive oxygen species generation at therapeutic levels. Despite these advantages, the utility of these chromophores has been limited by synthetic challenges associated with bacteriochlorophyll metallation; specifically, a slow reaction rate and necessity of complex purification procedures remain barriers towards metalated bacteriochlorophyll synthesis. Here, these limitations are overcome through the development of a new fast, facile, efficient, base-free microwave heating metallation method for the synthesis of a series of metallo (Pd, Cu, Zn, Cd, Sn, In, Mn, Co) bacteriopyropheophorbides. The preparation and structural and optical spectral characterization of these complexes are presented. This microwave-enabled synthetic method is then applied to generate the clinical photosensitizer agent Pd-bacteriopheophorbide (TOOKAD) effectively and efficiently, followed by validation of its metallation-enhanced ROS generation.

In this brief perspective, we describe key events in the history of the lipid-based nanomedicine field, highlight Canadian contributions, and outline areas where lipid nanoparticle technology is poised to have a transformative effect on the future of medicine.

Theranostic nanoparticles aim to integrate diagnostic imaging and therapy to facilitate image-guided treatment protocols. Herein, we present a theranostic nanotexaphyrin for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and focal photodynamic therapy (PDT) accomplished through the chelation of metal isotopes (In, Lu). To realize nanotexaphyrin's theranostic properties, we developed a rapid and robust

A pH-driven self-assembly of a simple aza-BODIPY was discovered in PBS solution, whereby ion-specific J-aggregated nanostructures were generated at very low dye concentration (2.5–20 [Formula: see text]M). The aggregation process was investigated in different conditions (pH, temperature and time) by monitoring absorption spectral shifts and associated nanostructure morphological changes. The pH-driven self-assembly process demonstrated an instantaneous thermodynamic phenomenon associated with three characteristic structures, each with distinctive optical properties. When the sample was first formulated within a short time window, a thermodynamically less stable intermediate with an unusual morphology of triangular nanoplates and broad absorption was observed. The formation of these structures was independent of the ions in PBS solution (Na[Formula: see text], K[Formula: see text], thus indicating that the triangular structure was inherent to the anisotropic structure of aza-BODIPY scaffolds. The second structure associated with a metastable pathway generated a uniform population of spherical nanovesicles, while the third structure, generated through a more thermodynamically stable pathway consisted of fibers. The absorption spectra suggested that both spherical and fiber structures contributed to the J-aggregation band at 735 nm in the near infrared optical spectrum and their population in each formulation was concentration dependent. The results highlighted the significance of ion effects in self-assembly of aza-BODIPY and the mechanistic structural changes of the morphology. Furthermore, this fundamental discovery offers a versatile method for the self-assembly of aza-BODIPY J-aggregates as a new nanoplatform with potential photonic applications.

Background Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform. Results PTX (3.1 wt%) and porphyrin (18.3 wt%) were loaded efficiently into PLNE-PTX, forming spherical core–shell nanoemulsions with a diameter of 120 nm. PLNE-PTX demonstrated stability in systemic delivery, resulting in high tumor accumulation (~ 5.4 ID %/g) in KB-tumor bearing mice. PLNE-PTX combination therapy inhibited tumor growth (78%) in an additive manner, compared with monotherapy PDT (44%) or chemotherapy (46%) 16 days post-treatment. Furthermore, a fourfold reduced PTX dose (1.8 mg PTX/kg) in PLNE-PTX combination therapy platform demonstrated superior therapeutic efficacy to Taxol at a dose of 7.2 mg PTX/kg, which can reduce side effects. Moreover, the intrinsic fluorescence of PLNE-PTX enabled real-time tracking of nanoparticles to the tumor, which can help inform treatment planning. Conclusion PLNE-PTX combining PDT and chemotherapy in a single platform enables superior anti-tumor effects and holds potential to reduce side effects associated with monotherapy chemotherapy. The inherent imaging modality of PLNE-PTX enables real-time tracking and permits spatial and temporal regulation to improve cancer treatment. Graphic Abstract

Exploitation of photosensitizers as payloads for antibody-based anticancer therapeutics offers a novel alternative to the small pool of commonly utilized cytotoxins. However, existing bioconjugation methodologies are incompatible with the requirement of increased antibody loading without compromising antibody function, stability, or homogeneity. Herein, we describe the first application of dendritic multiplier groups to allow the loading of more than 4 porphyrins to a full IgG antibody in a site-specific and highly homogeneous manner. Photophysical evaluation of UV-visible absorbance and singlet oxygen quantum yields highlighted porphyrin-dendron 14 as the best candidate for bioconjugation; with subsequent bioconjugation producing a HER2-targeted therapeutic with average loading ratios of 15.4:1. In vitro evaluation of conjugate 18 demonstrated a nanomolar photocytotoxic effect in a target cell line, which overexpresses HER2, with no observed photocytotoxicity at the same concentration in a control cell line which expresses native HER2 levels, or in the absence of irradiation with visible light.

Fluorescence is an essential imaging modality for labelling and visualising cells and sub-cellular structures. Multicolour labelling is especially challenging due to differences in physicochemical and photophysical behaviour of structurally unrelated fluorophores in the heterogeneous environments found in sub-cellular compartments. Herein, we report the conjugation of three azide-bearing BODIPYs with similar core structures but widely different emission wavelengths (green, red and NIR) to tyrosine residues of a model globular protein (BSA) via a common linking methodology. The resulting BODIPY-BSA conjugates have demonstrated multi-wavelength fluorescence emission for biological applications. Fluorescence imaging was performed in HeLa cells through live cell confocal microscopy imaging, with good intracellular location visualisation observed.

Hypoxia is a ubiquitous feature of solid tumors, which plays a key role in tumor angiogenesis and resistance development. Conventional hypoxia detection methods lack continuous functional detection and are generally less suitable for dynamic hypoxia measurement. Optical sensors hereby provide a unique opportunity to noninvasively image hypoxia with high spatiotemporal resolution and enable real-time detection. Therefore, these approaches can provide a valuable tool for personalized treatment planning against this hallmark of aggressive cancers. Many small optical molecular probes can enable analyte triggered response and their photophysical properties can also be fine-tuned through structural modification. On the other hand, optical nanoprobes can acquire unique intrinsic optical properties through nanoconfinement as well as enable simultaneous multimodal imaging and drug delivery. Furthermore, nanoprobes provide biological advantages such as improving bioavailability and systemic delivery of the sensor to enhance bioavailability. This review provides a comprehensive overview of the physical, chemical, and biological analytes for cancer hypoxia detection and focuses on discussing the latest nano- and molecular developments in various optical imaging approaches (fluorescence, phosphorescence, and photoacoustic) in vivo. Finally, this review concludes with a perspective toward the potentials of these optical imaging approaches in hypoxia detection and the challenges with molecular and nanotechnology design strategies.

We herein report the synthesis and analysis of a novel aza-BODIPY-antibody conjugate, formed by controlled and regioselective bioconjugation methodology. Employing the clinically relevant antibody, which targets HER2 positive cancers, represents an excellent example of an antibody targeting strategy for this class of near-IR emitting fluorophore. The NIR fluorescence and binding properties were validated through in vitro studies using live cell confocal imaging.

The discovery and synthesis of multifunctional organic building blocks for nanoparticles have remained challenging. Texaphyrin macrocycles are multifunctional, all-organic compounds that possess versatile metal-chelation capabilities and unique theranostics properties for biomedical applications. Unfortunately, there are significant difficulties associated with the synthesis of texaphyrin-based subunits capable of forming nanoparticles. Herein, the detailed synthesis of a texaphyrin-phospholipid building block is reported via a key 1,2-dinitrophenyl-phospholipid intermediate, along with stable chelation of two clinically relevant metal ions into texaphyrin-lipid without compromising their self-assembly into texaphyrin nanoparticles or nanotexaphyrin. A postinsertion methodology to quantitatively insert a variety of metal-ions into preformed nanotexaphyrins is developed and employed to synthesize a structurally stable, mixed 111 indium-manganese-nanotexaphyrin for dual modal single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). In vivo dual SPECT/MRI imaging of 111 In-Mn-nanotexaphyrins in an orthotopic prostatic PC3 mouse model demonstrates complementary signal enhancement in the tumor with both modalities at 22 h post intravenous administration. This result highlights the utility of hybrid metallo-nanotexaphyrins to achieve sensitive and accurate detection of tumors by accommodating multiple imaging modalities. The power of this mixed and matched metallo-nanotexaphyrin strategy can be unleashed to allow a diverse range of multifunctional biomedical imaging.

Additional file 1: Figure S1. Ex vivo tissue fluorescence imaging at 24 h post injection of PLNEnoPEG versus PLNE. Figure S2. (A) UV-vis spectrum and (B) fluorescence spectrum of intact PLNE-PTX (ddH2O) or disrupted PLNE-PTX (ddH2O containing 1% Triton X-100). Figure S3. Blood clearance curve of PLNE-PTX exhibited short half-life of t1/2α= 0.52 ±0.39 h and long half-life of t1/2β = 3.10 ± 0.34 h (n=5) by two-phase exponential decayanalysis. Figure S4. Representative tumor photographs in tracking tumor growth withtime for each group after treatment.

Additional file 1: Figure S1. Ex vivo tissue fluorescence imaging at 24 h post injection of PLNEnoPEG versus PLNE. Figure S2. (A) UV-vis spectrum and (B) fluorescence spectrum of intact PLNE-PTX (ddH2O) or disrupted PLNE-PTX (ddH2O containing 1% Triton X-100). Figure S3. Blood clearance curve of PLNE-PTX exhibited short half-life of t1/2α= 0.52 ±0.39 h and long half-life of t1/2β = 3.10 ± 0.34 h (n=5) by two-phase exponential decayanalysis. Figure S4. Representative tumor photographs in tracking tumor growth withtime for each group after treatment.