How smart can polymers be? Prepare to be amazed!
Smart polymers (or stimuli-responsive polymers) change their physical properties according to the environment and can respond to temperature, pH, light, humidity, or electrical or magnetic field with a change in color, transparency, conductivity, permeability, or shape.
Scientists from University of Texas Southwestern Medical Center went a step further and organized polymers into “smart” nanomicelles. Micelles are small, round particles, organized in liquid by self-assembly of amphiphilic macromolecules, consisting of both hydrophilic and hydrophobic monomer units. What made them smart was their extreme pH sensitivity. And due to their small size, the nanomicelles were able to freely travel through the bloodstream and recognize solid tumors. A research paper, “A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals,” published in Nature Materials, explains:
Stimuli-responsive nanomaterials are increasingly important in a variety of applications such as biosensing, molecular imaging, drug delivery and tissue engineering. For cancer detection, a paramount challenge still exists in the search for methods that can illuminate tumours universally regardless of their genotypes and phenotypes. Here we capitalized on the acidic, angiogenic tumour microenvironment to achieve the detection of tumour tissues in a wide variety of mouse cancer models.
This was accomplished using ultra pH-sensitive fluorescent nanoprobes that have tunable, exponential fluorescence activation on encountering subtle, physiologically relevant pH transitions. These nanoprobes were silent in the circulation, and then strongly activated (>300-fold) in response to the neovasculature or to the low extracellular pH in tumours.
The design of pH-sensitive nanoprobes was based on the principles of supramolecular self-assembly of ionizable block copolymer micelles, published by the same group of scientists in Angewandte Chemie in 2011.
The pH-sensitive micelles are assembled from block copolymers obtained by atom transfer radical polymerization with a hydrophobic segment, containing tertiary amine and a hydrophilic segment. pH-insensitive fluorophore is conjugated to the hydrophobic polymer block.
At higher pH, the amine is uncharged and the block copolymer molecules self-assemble into micelles with a hydrophobic core, resulting in the aggregation of fluorophores and quenching of the fluorescence signals through the mechanisms of Förster resonance energy transfer between the fluorophores (homo-FRET), and photoinduced electron transfer from tertiary amines to fluorophores.
At lower pH, the amine becomes protonated and positively charged, leading to micelle disassembly and dramatic increase of fluorescence emission due to the increased distance between the fluorophores and amines.
Tumor-specific fluorescent imaging was achieved with 20 nm pH-activatable micelles, consisting from poly(ethylene glycol)-b-poly(2-(hexamethyleneimino)ethyl methacrylate) copolymer with conjugated fluorescent dye (Cy5.5). The nanomicelle probes could distinguish the small pH differences between acidic tumor pH (6.5-6.8) and blood (7.4), lighting up only in the tumor. It was also possible to target the nanoparticles further into specific cell organelles using specific peptides. As a result, specific imaging of brain, pancreatic, breast, and prostate solid tumors was demonstrated in mice, both in vitro and in vivo.
Tumour-specific imaging was accomplished in the first hour after intravenous nanoprobe injection and in tumours as small as 1mm3. These capabilities, together with the broad cancer specificity, make the present strategy particularly powerful in image-guided resection of tumours and post-therapy monitoring of drug efficacy.
Indeed, some molecules are smart! So are their creators. …
Source: Brighter future for cancer detection with polymer probe, Tim Wogan, rcs.org, 11 December 2013
Source: A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals, Y Wang et al, Nat. Mater., 2013, DOI: 10.1038/nmat3819 08 December 2013
Source: Tunable, ultrasensitive pH-responsive nanoparticles targeting specific endocytic organelles in living cells, Zhou K. et al., Angew Chem Int Ed Engl. 2011 Jun 27;50(27):6109-14. doi: 10.1002/anie.201100884.
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