Biomimetic Approach to Promote Cellular Uptake and Enhance Photoacoustic Properties of Tumor-Seeking Dyes

Abstract

The attachment of glucose to drugs and imaging agents enables cancer cell targeting via interactions with GLUT1 overexpressed on the cell surface. While an added benefit of this modification is the solubilizing effect of carbohydrates, in the context of imaging agents, aqueous solubility does not guarantee decreased π-stacking or aggregation. The resulting broadening of the absorbance spectrum is a detriment to photoacoustic (PA) imaging since the signal intensity, accuracy, and image quality all rely on reliable spectral unmixing. To address this major limitation and further enhance the tumor-targeting ability of imaging agents, we have taken a biomimetic approach to design a multivalent glucose moiety (mvGlu). We showcase the utility of this new group by developing aza-BODIPY-based contrast agents boasting a significant PA signal enhancement greater than 11-fold after spectral unmixing. Moreover, when applied to targeting cancer cells, effective staining could be achieved with ultra-low dye concentrations (50 nM) and compared to a non-targeted analogue, the signal intensity was >1000-fold higher. Lastly, we employed the mvGlu technology to develop a logic-gated acoustogenic probe to detect intratumoral copper (i.e., Cu(I)), which is an emerging cancer biomarker, in a murine model of breast cancer. This exciting application was not possible using other acoustogenic probes previously developed for copper sensing.

Hydrogen Sulfide Responsive Phototherapy Agents: Design Strategies and Biological Applications

“…One option in this direction is to utilize cell surface receptors (e.g., biotin, folate, human epidermal growth factor, etc.) that are differentially expressed in cancer cells. − To this end, PSs are modified with specific groups that can bind to the receptor of interest selectively. Tumor-homing peptides, which are capable of penetrating the cell membrane, recognizing tumor-related antigens or proteins, and binding to specific cell surfaces, are highly popular.…”

“…Tumor-homing peptides, which are capable of penetrating the cell membrane, recognizing tumor-related antigens or proteins, and binding to specific cell surfaces, are highly popular. The most well-known tumor-homing peptide, RGD, is composed of a tripeptide chain (Arg-Gly-Asp) and binds to integrins α V β 3 and α V β 5 . ,, NGR is also composed of a tripeptide chain (Asp-Gly-Arg) and exhibits specific selectivity toward aminopeptidase N. , Chlorotoxins, a small group of peptide toxins derived from scorpion venom, have been employed as targeting units in various studies, but they are particularly used for glioblastoma. , In addition to the peptide family, glucose metabolism can be targeted via glucose transporters. ,, Proteins such as transferrin and apolipoproteins have also been employed as targeting moieties. ,, Furthermore, a range of vitamins have been utilized as cancer targeting ligands …”

Resolving atomic-level dynamics and interactions of high molecular weight hyaluronic acid by multidimensional solid-state NMR

“…We used a biomimicking ECM mixture called Geltrex™ matrix which has the same major components (laminin, entactin, collagen type IV, and heparin sulphate proteoglycans) as the biological ECM, except for the crucial component HA. This type of mixture is commonly used to prepare ECM-like hydrogels for cell culture and other applications 34,35 . The 13 C-labeled HMW-HA was mixed with ECM and a HA-ECM hydrogel was prepared.…”

Chemical Approaches to Optimize the Properties of Organic Fluorophores for Imaging and Sensing

“…[49] Recently, Chan and colleagues introduced the hydrophilic glucose moieties into aza-BODIPY, and significantly increase the water solubility (defined as the water-oil distribution coefficient, LogD, with much poorer water solubility (logD = 2.51 � 0.92) for 39 compared with 40 (logD = 0.75 � 0.02), 41 (logD = À 1.12 � 0.16), and 42 (logD = À 0.71 � 0.11)), accompanied with the enlarged extinction coefficient and quantum yield, accompanied by improvements of extinction coefficient and quantum yield. [50] In 2020, Smith and colleagues designed a three-dimensional architecture, and installed two hydrophilic arms (PEGs) on meso-aryl substituent of 35. [51] The two arms are over each of polyene, and exactly shield the rigid hydrophobic core (heptamethine skeletons) (37), relieve the dye/dye self-aggregation, and improve extinction coefficient.…”

“…For example, heptamethine cyanine dyes containing multiple anionic and non‐ionic substituents display better water solubility and higher brightness than traditional Cy7 (35, 36) [49] . Recently, Chan and colleagues introduced the hydrophilic glucose moieties into aza‐BODIPY, and significantly increase the water solubility (defined as the water‐oil distribution coefficient, LogD, with much poorer water solubility (logD=2.51±0.92) for 39 compared with 40 (logD=0.75±0.02), 41 (logD=−1.12±0.16), and 42 (logD=−0.71±0.11)), accompanied with the enlarged extinction coefficient and quantum yield, accompanied by improvements of extinction coefficient and quantum yield [50] . In 2020, Smith and colleagues designed a three‐dimensional architecture, and installed two hydrophilic arms (PEGs) on meso‐aryl substituent of 35 [51] .…”