1. Efficient acid-catalyzed (18) F/(19) F fluoride exchange of BODIPY dyes
Edmund J Keliher, Jenna A Klubnick, Thomas Reiner, Ralph Mazitschek, Ralph Weissleder ChemMedChem. 2014 Jul;9(7):1368-73. doi: 10.1002/cmdc.201300506. Epub 2014 Mar 5.
Fluorine-containing fluorochromes are important validation agents for positron emission tomography imaging compounds, as they can be readily validated in cells by fluorescence imaging. In particular, the (18) F-labeled BODIPY-FL fluorophore has emerged as an important platform, but little is known about alternative (18) F-labeling strategies or labeling on red-shifted fluorophores. In this study we explore acid-catalyzed (18) F/(19) F exchange on a range of commercially available N-hydroxysuccinimidyl ester and maleimide BODIPY fluorophores. We show this method to be a simple and efficient (18) F-labeling strategy for a diverse span of fluorescent compounds, including a BODIPY-modified PARP-1 inhibitor, and amine- and thiol-reactive BODIPY fluorophores.
2. Development of l-Amino-Acid-Based Hydroxyl Functionalized Biodegradable Amphiphilic Polyesters and Their Drug Delivery Capabilities to Cancer Cells
Sonashree Saxena, Manickam Jayakannan Biomacromolecules. 2020 Jan 13;21(1):171-187. doi: 10.1021/acs.biomac.9b01124. Epub 2019 Oct 22.
Hydroxyl-functionalized amphiphilic polyesters based on l-amino acid bioresources were designed and developed, and their nanoassemblies were explored as intracellular enzyme-biodegradable scaffolds for delivering anticancer drugs and fluorophores to cancer cells. To accomplish this task, acetal-masked multifunctional dicarboxylic ester monomer from l-aspartic acid was tailor-made, and it was subjected to solvent-free melt transesterification polycondensation with commercial diols to produce acetal-functionalized polyesters. Acid-catalyzed postpolymerization deprotection of these acetal-polyesters produced amphiphilic hydroxyl-functionalized polyesters. The amphiphilic polyesters were self-assembled in aqueous medium to produce nanoparticles of size <200 nm. Wide ranges of both water-soluble and water-insoluble anticancer drugs such as doxorubicin (DOX), camptothecin (CPT), and curcumin (CUR) and fluorophores such as Nile red (NR), Rose Bengal (RB), and Congo red (CR) were encapsulated in hydroxyl polyesters nanoparticles. In vitro drug release studies revealed that the aliphatic polyester backbone underwent lysosomal enzymatic-biodegradation to release the loaded cargoes at the intracellular compartments. Lysotracker-assisted live-cell confocal microscopy studies further confirmed the colocalization of the polymer nanoscaffolds in the lysosomes and supported their enzymatic-biodegradation for drug delivery. In vitro cytotoxicity studies showed that the nascent polymers were not toxic, whereas their anticancer drug-loaded nanoparticles exhibited excellent cell killing in cervical cancer (HeLa) cell lines. The drug-loaded (CPT, CUR, and DOX) and the fluorophore-loaded (NR, RB, and CR) polymer nanoparticles were highly luminescent; thus, the encapsulated polymer nanoparticles enabled the multiple color-tunable bioimaging in cancer cells in the entire visible region from blue to deep red. Time-dependent live-cell confocal microscopy studies established that the cellular uptake of drugs and fluorophores was 5 to 10-fold higher while they were delivered from the hydroxyl polyester platform. The hydroxyl polyester nanocarrier design strategy opens up new opportunities in drug delivery to cancer cells from a biodegradable polymer platform based on l-amino acids.
3. Aliphatic hyperbranched polyester: a new building block in the construction of multifunctional nanoparticles and nanocomposites
Santimukul Santra, Charalambos Kaittanis, J Manuel Perez Langmuir. 2010 Apr 20;26(8):5364-73. doi: 10.1021/la9037843.
Herein we report the design and synthesis of multifunctional hyperbranched polyester-based nanoparticles and nanocomposites with properties ranging from magnetic, fluorescence, antioxidant and X-ray contrast. The fabrication of these nanostructures was achieved using a novel aliphatic and biodegradable hyperbranched polyester (HBPE) synthesized from readily available diethyl malonate. The polymer's globular structure with functional surface carboxylic groups and hydrophobic cavities residing in the polymer's interior allows for the formation of multifunctional polymeric nanoparticles, which are able to encapsulate a diversity of hydrophobic cargos. Via simple surface chemistry modifications, the surface carboxylic acid groups were modified to yield nanoparticles with a variety of surface functionalizations, such as amino, azide and propargyl groups, which mediated the conjugation of small molecules. This capability achieved the engineering of the HBPE nanoparticle surface for specific cell internalization studies and the formation of nanoparticle assemblies for the creation of novel nanocomposites that retained, and in some cases enhanced, the properties of the parental nanoparticle building blocks. Considering these results, the HBPE polymer, nanoparticles and composites should be ideal for biomedical, pharmaceutical, nanophotonics applications.
