Nanoparticle-Aptamer Bioconjugates

Abstract

Nucleic acid ligands (aptamers) are potentially well suited for the therapeutic targeting of drug encapsulated controlled release polymer particles in a cell-or tissue-specific manner. We synthesized a bioconjugate composed of controlled release polymer nanoparticles and aptamers and examined its efficacy for targeted delivery to prostate cancer cells. Specifically, we synthesized poly(lactic acid)-block-polyethylene glycol (PEG) copolymer with a terminal carboxylic acid functional group (PLA-PEG-COOH), and encapsulated rhodamine-labeled dextran (as a model drug) within PLA-PEG-COOH nanoparticles. These nanoparticles have the following desirable characteristics: (a) negative surface charge (؊50 ؎ 3 mV, mean ؎ SD, n ‫؍‬ 3), which may minimize nonspecific interaction with the negatively charged nucleic acid aptamers; (b) carboxylic acid groups on the particle surface for potential modification and covalent conjugation to amine-modified aptamers; and (c) presence of PEG on particle surface, which enhances circulating half-life while contributing to decreased uptake in nontargeted cells. Next, we generated nanoparticle-aptamer bioconjugates with RNA aptamers that bind to the prostate-specific membrane antigen, a well-known prostate cancer tumor marker that is overexpressed on prostate acinar epithelial cells. We demonstrated that these bioconjugates can efficiently target and get taken up by the prostate LNCaP epithelial cells, which express the prostate-specific membrane antigen protein (77-fold increase in binding versus control, n ‫؍‬ 150 cells per group). In contrast to LNCaP cells, the uptake of these particles is not enhanced in cells that do not express the prostate-specific membrane antigen protein. To our knowledge, this represents the first report of targeted drug delivery with nanoparticle-aptamer bioconjugates.

Core-controlled polymorphism in virus-like particles

“…Au cores of 15 nm and larger were more heterogeneous, in terms of size and shape, than the smaller cores. However, when the VLPs obtained from 15-nm cores were sorted by diameter, similar distributions of VLP (21,26, and 28 nm) were observed. These results suggest that the formation of VLPs is constrained by subunit interactions.…”

“…Symmetric VLPs may provide a technology for therapeutic or diagnostic agent delivery that is improved over amorphous shell nanoparticles that are already known to be efficient in similar applications (21). The advantage of a regular surface protein motif is that the binding domains are functionally identical by virtue of their equivalent environment.…”

Quantum dots–DNA bioconjugates: synthesis to applications

“…The QDs are first coated with ligands that bear carboxylic acid functional groups. These ligands are either small molecules such as MAA (mercapto acetic acid), MPA, MHA and DHLA [35,42,80,81] or derived polymeric scaffolds terminating in carboxylic acid [82,86]. To all of these QDs 'terminating' in solvent-exposed carboxylic acid functional groups, conjugation of amine-functionalized DNA is carried out in the presence of EDC and NHS.…”

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

“…Xiao et al have recently developed a cell-uptake strategy to discover efficient targeting ligands and exclude noninternalizing ligands. [550] Since the report of targeting the prostate-specific membrane antigen (PSMA) by aptamer-decorated nanoparticles in 2004, [551] a vast range of in vivo and in vitro researches have been conducted to prove the effectiveness of aptamers in targeted delivery of multiple types of drugs and imaging applications. [552] Dhar et al synthesized nanoparticles decorated with aptamers having high affinity for PSMA to deliver cisplatin (a platinum-based chemotherapeutic) to prostate cancer cells.…”