Hyaluronic Acid/Poly(β‐Amino Ester) Polymer Nanogels for Cancer‐Cell‐Specific NIR Fluorescence Switch

Abstract

Cancer-cell-specific pH-activatable polymer nanogels consisting of CD44-receptor-targeting hyaluronic acid (HA), pH-sensitive poly(β-amino ester) (PBAE), and near-infrared (NIR) fluorescent indocyanine green (ICG) were synthesized and used to detect cancer cells. The HA/PBAE/ICG-polymer-nanogel-based NIR probe was nonfluorescent outside of tumor cells. After internalization by CD44-receptor-mediated endocytosis, the probe accumulated in the late endosomes or lysosomes where the acidic pH solubilized the PBAE and caused instant disassembly of the polymer nanogel. During endosomal maturation, the encapsulated ICG was released from its quenched state, inducing strong NIR fluorescence recovery. The nanogels generate a highly tumor-specific NIR signal with a reduced background signal.

Nanogels: An overview of properties, biomedical applications and obstacles to clinical translation

“…Under normal physiological conditions, the ICG fluorescence was quenched in the intact nanogels. Once ICG-loaded nanogel is internalized by receptor-mediated endocytosis, PBAE is degraded in the acidic environment of endosomes and lysosomes, gradually releasing ICG, thus generating a fluorescence signal [187]. In a similar vein, hyaluronic acid was used to prepare nanogels that could be used for monitoring hyaluronidase activity in vivo , as it is associated with tumor metastasis and angiogenesis.…”

Soft fluorescent nanomaterials for biological and biomedical imaging

“…pH-activable fluorescent nanogels were also reported by self-assembly of a copolymer consisting of a targeting ligand HA, a pH-sensitive unit PBAE and an ICG copolymer. 119 ICG dyes are in quenched state when encapsulated by nanogels, but acidic pH can solubilize the PBAE units and recover the fluorescence of the ICG by releasing them from nanogels. 66 …”

“…Examples include peptides (F3-Cys), 67 vitamins, sugars (e.g. glucose 107 and hyaluronic acid 119 ) and aptamers. 139 Folic acid also is widely adopted for this purpose because it selectively binds to folate receptors that are over-expressed in tumor cells.…”

A novel DAD type and folic acid conjugated fluorescent monomer as a targeting probe for imaging of folate receptor overexpressed cells

“…Recently, fluorescence cellular imaging attracts great attention in life science and medical applications . Fluorescent probes and dyes are widely used and due to their small size, fluorescence power and ease in applicability, these organic dyes and probes are of interest in imaging studies . The preferred materials used in imaging studies should be chemically and photostable, non‐toxic, have strong emission and give possibility to long term imaging without bleaching .…”

“…[1][2][3] Fluorescent probes and dyes are widely used and due to their small size, fluorescence power and ease in applicability, these organic dyes and probes are of interest in imaging studies. [4][5][6] The preferred materials used in imaging studies should be chemically and photostable, non-toxic, have strong emission and give possibility to long term imaging without bleaching. 7 For this reason, small molecules for imaging purposes play a pivotal role with their compatibility and performance as imaging probes.…”