Inspired by the simplicity and versatility of layer-by-layer (LbL) assembly, we apply multilayered polyelectrolyte assemblies on nanoparticles to create viable systemic delivery systems. Focusing on tumor specific delivery, LbL nanoparticles that exhibit a pH sensitive outer stealth layer are demonstrated to target and be retained in hypoxic tumor regions. The neutral layers shed in response to acidity to reveal a charged nanoparticle surface that is readily taken up by tumor cells. The first in vivo demonstration of this mechanism of targeting is presented, as well as an initial examination of mechanism of uptake of the nanoparticles. We further demonstrate that this concept for tumor targeting is potentially valid for a broad range of cancers, with applicability for therapies that target hypoxic tumor tissue.

A series of poly(arylene ethynylene) (PAE) conjugated polyelectrolytes (CPEs) have been prepared using palladium-mediated (Sonogashira) coupling chemistry. The series consists of five pairs of polymers that share the same poly(arylene ethynylene) backbone. One member of each pair contains anionic sulfonate (R−SO3 -) side groups, whereas the other member contains cationic bis-alkylammonium (R-N+−R-N+−R) side groups. The repeat unit structure of the poly(arylene ethynylene) backbone consists of a bis(alkoxy)phenylene-1,4-ethynylene unit alternating with a second arylene ethynylene moiety, and five different arylenes were used, Ar = 1,4-phenyl, 2,5-pyridyl (Py), 2,5-thienyl (Th), 2,5-(3,4-ethylenedioxy)thienyl (EDOT), and 1,4-benzo[2,1,3]thiodiazole (BDT). The different arylene units induce variation in the HOMO−LUMO band gap across the series of polymers, resulting in a series of materials that display absorption maxima at wavelengths ranging from 400 to 550 nm and fluorescence maxima ranging from 440 to 600 nm. The absorption and fluorescence properties of the CPEs were investigated in methanol, water, and in methanol/water mixtures. The photophysical data suggest that the CPE chains aggregate in water, but in methanol, the polymers are well solvated such that the optical properties are characteristic of the “molecularly dissolved” chains. Stern−Volmer (SV) fluorescence quenching studies were carried out using ionic naphthalene diimides as electron acceptors. The results show that the fluorescence from the CPEs was quenched with very high efficiency (amplified quenching) when the ionic diimide was charged opposite to the charge on the CPE chain. The sensitivity of the Stern−Volmer quenching response varies strongly across the series of CPEs, with the most efficient quenching seen for polymers that display efficient fluorescence when they are aggregated. The relationship between CPE side chain structure, band gap, fluorescence quantum yield, extent of chain aggregation, and fluorescence quenching efficiency is discussed.

We set out to determine whether a minimally invasive approach for one-level instrumented posterior lumbar interbody fusion reduced undesirable changes in the multifidus muscle, compared to a conventional open approach. We also investigated associations between muscle injury during surgery (creatinine kinase levels), clinical outcome and changes in the multifidus at followup. We studied 59 patients treated by one team of surgeons at a single institution (minimally invasive approach in 28 and conventional open approach in 31, voluntarily chosen by patients). More than 1 year postoperatively, all the patients were followed up with the visual analogue scale (VAS) and Oswestry disability index (ODI), and 16 patients from each group were evaluated using MRI. This enabled the cross-sectional area (CSA) of lean multifidus muscle, and the T2 signal intensity ratio of multifidus to psoas muscle, to be compared at the operative and adjacent levels. The minimally invasive group had less postoperative back pain (P \ 0.001) and lower postoperative ODI scores (P = 0.001). Multifidus atrophy was less in the minimally invasive group (P \ 0.001), with mean reductions in CSA of 12.2% at the operative and 8.5% at the adjacent levels, compared to 36.8% and 29.3% in the conventional open group. The increase in the multifidus:psoas T2 signal intensity ratio was similarly less marked in the minimally invasive group where values increased by 10.6% at the operative and 8.3% at the adjacent levels, compared to 34.4 and 22.7% in the conventional open group (P \ 0.001). These changes in multifidus CSA and T2 signal intensity ratio were significantly correlated with postoperative creatinine kinase levels, VAS scores and ODI scores (P \ 0.01). The minimally invasive approach caused less change in multifidus, less postoperative back pain and functional disability than conventional open approach. Muscle damage during surgery was significantly correlated with long-term multifidus muscle atrophy and fatty infiltration. Furthermore these degenerative changes of multifidus were also significantly correlated with long-term clinical outcome.

Minimally invasive TLIF as a management of 1-level degenerative lumbar diseases is superior to the traditional open procedure in terms of postoperative back pain, total blood loss, need for transfusion, time to ambulation, length of hospital stay, soft-tissue injury, and functional recovery. However, this procedure takes longer operative duration and requires close attention to the risk of technical complications. Longer-term studies involving a larger sample are needed to validate the long-term efficacy of minimally TLIF.