Modular Integration of Upconverting Nanocrystal–Dendrimer Composites for Folate Receptor‐Specific NIR Imaging and Light‐Triggered Drug Release

Abstract

Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system.

Folic Acid Functionalized Zirconium‐Based Metal–Organic Frameworks as Drug Carriers for Active Tumor‐Targeted Drug Delivery

“…As for other types of drug carriers, attempts to introduce an active tumor targeting function have been successfully realized . In addition, attaching folic acid (FA) onto these drug carriers has proven to be effective for building an active targeting drug‐delivery system for tumors, due to the high concentration of folate receptor in tumor tissues …”

Control of an Unusual Photo-Claisen Rearrangement in Coumarin Caged Tamoxifen through an Extended Spacer

“…The contributions of their applications have been well documented in numerous fields ranging from ion channels 1,13 and enzymes 14,15 to gene expression, 16 photopharmacology, 17,18 and controlled drug transport or delivery. 19−21 …”

Synthesis and preliminary evaluation of a 99mTc‐labeled folate‐PAMAM dendrimer for FR imaging

“…In other words, it is feasible to synthesize mono‐, di‐, and even multifunctionalized conjugates using PAMAM dendrimer as platform with facile modification methods. By different components' assembly, targeting groups, therapeutic elements, and imaging reagents were mixed with PAMAM dendrimer platform simultaneously or sequentially to give mono‐, di‐, and multifunctional conjugates for different uses . These achievements have shown brilliant future to the final implementation of “extensible and modular platform.” Further studies are under way to implement these ideas by using more sophisticated functional groups based on more efficient synthetic scheme.…”