30 research outputs found
Bioorthogonal Oxime Ligation Mediated in vivo Cancer Targeting
Current cancer targeting relying on specific biological interaction between the cell surface antigen and respective antibody or its analogue has proven to be effective in the treatment of different cancers; however, this strategy has its own limitations, such as the heterogeneity of cancer cells and immunogenicity of the biomacromolecule binding ligands. Bioorthogonal chemical conjugation has emerged as an attractive alternative to biological interaction for in vivo cancer targeting. Here, we report an in vivo cancer targeting strategy mediated by bioorthogonal oxime ligation. An oxyamine group, the artificial target, is introduced onto 4T1 murine breast cancer cells through liposome delivery and fusion. Poly(ethylene glycol)-polylactide (PEG-PLA) nanoparticles (NPs) are surface-functionalized with aldehyde groups as targeting ligands. The improved in vivo cancer targeting of PEG-PLA NPs is achieved through specific and efficient chemical reaction between the oxyamine and aldehyde groups
Molecular Imaging and Nanotechnology—Emerging Tools in Diagnostics and Therapy
Personalized medicine is emerging as a new goal in the diagnosis and treatment of diseases. This approach aims to establish differences between patients suffering from the same disease, which allows to choose the most effective treatment. Molecular imaging (MI) enables advanced insight into molecule interactions and disease pathology, improving the process of diagnosis and therapy and, for that reason, plays a crucial role in personalized medicine. Nanoparticles are widely used in MI techniques due to their size, high surface area to volume ratio, and multifunctional properties. After conjugation to specific ligands and drugs, nanoparticles can transport therapeutic compounds directly to their area of action and therefore may be used in theranostics—the simultaneous implementation of treatment and diagnostics. This review summarizes different MI techniques, including optical imaging, ultrasound imaging, magnetic resonance imaging, nuclear imaging, and computed tomography imaging with theranostics nanoparticles. Furthermore, it explores the potential use of constructs that enables multimodal imaging and track diseases in real time
Amphiphilic Molecules Exhibiting Zwitterionic Excited-State Intramolecular Proton Transfer and Near-Infrared Emission for the Detection of Amyloid β Aggregates in Alzheimer’s Disease
Chromophores with zwitterionic excited-state intramolecular proton transfer (ESIPT) have been shown to have larger Stock shifts and red-shifted emission wavelengths compared to the conventional π-delocalized ESIPT molecules. However, there is still a dearth of design strategies to expand the current library of zwitterionic ESIPT compounds. Herein, we report a novel zwitterionic excited-state intramolecular proton transfer system enabled by addition of triazamacrocycle (TACN) fragments on a dicyanomethylene-4H-pyran (DCM) scaffold. The solvent-dependent steady-state photophysical studies and pKa measurements strongly support that the ESIPT process is more efficient with two TACN groups attached to the DCM scaffold and not affected by polar protic solvents. Impressively, compound DCM-OH-2-DT emits with a near-infrared (NIR) emission wavelength at 740 nm along with an uncommonly large Stokes shift of ~ 280 nm. Moreover, DCM-OH-2-DT shows high affinity towards soluble amyloid β (Aβ) oligomers in vitro and in 5xFAD mouse brain sections, and we have successfully applied DCM-OH-2-DT for the NIR fluorescence in vivo imaging of Aβ aggregates and demonstrated its potential use as an early diagnostic agent for AD. Overall, this study can provide a general molecular design strategy for developing new zwitterionic ESIPT compounds with NIR emission for further in vivo imaging applications
Efficient Targeting of Adipose Tissue Macrophages in Obesity with Polysaccharide Nanocarriers
Obesity
leads to an increased risk for type 2 diabetes, heart disease,
stroke, and cancer. The causal link between obesity and these pathologies
has recently been identified as chronic low-grade systemic inflammation
initiated by pro-inflammatory macrophages in visceral adipose tissue.
Current medications based on small-molecule drugs yield significant
off-target side effects with long-term use, and therefore there is
a major need for targeted therapies. Here we report that nanoscale
polysaccharides based on biocompatible glucose polymers can efficiently
target adipose macrophages in obese mice. We synthesized a series
of dextran conjugates with tunable size linked to contrast agents
for positron emission tomography, fluorophores for optical microscopy,
and anti-inflammatory drugs for therapeutic modulation of macrophage
phenotype. We observed that larger conjugates efficiently distribute
to visceral adipose tissue and selectively associate with macrophages
after regional peritoneal administration. Up to 63% of the injected
dose remained in visceral adipose tissue 24 h after administration,
resulting in >2-fold higher local concentration compared to liver,
the dominant site of uptake for most nanomedicines. Furthermore, a
single-dose treatment of anti-inflammatory conjugates significantly
reduced pro-inflammatory markers in adipose tissue of obese mice.
Importantly, all components of these therapeutic agents are approved
for clinical use. This work provides a promising nanomaterials-based
delivery strategy to inhibit critical factors leading to obesity comorbidities
and demonstrates a unique transport mechanism for drug delivery to
visceral tissues. This approach may be further applied for high-efficiency
targeting of other inflammatory diseases of visceral organs