Nanoagents Based on Poly(ethylene glycol)-b-Poly(l-thyroxine) Block Copolypeptide for Enhanced Dual-Modality Imaging and Targeted Tumor Radiotherapy.

Future healthcare requires development of novel theranostic agents that are capable of not only enhancing diagnosis and monitoring therapeutic responses but also augmenting therapeutic outcomes. Here, a versatile and stable nanoagent is reported based on poly(ethylene glycol)-b-poly(l-thyroxine) (PEG-PThy) block copolypeptide for enhanced single photon emission computed tomography/computed tomography (SPECT/CT) dual-modality imaging and targeted tumor radiotherapy in vivo. PEG-PThy acquired by polymerization of l-thyroxine-N-carboxyanhydride (Thy-NCA) displays a controlled Mn , high iodine content of ≈49.2 wt%, and can spontaneously form 65 nm-sized nanoparticles (PThyN). In contrast to clinically used contrast agents like iohexol and iodixanol, PThyN reveals iso-osmolality, low viscosity, and long circulation time. While PThyN exhibits comparable in vitro CT attenuation efficacy to iohexol, it greatly enhances in vivo CT imaging of vascular systems and soft tissues. PThyN allows for surface decoration with the cRGD peptide achieving enhanced CT imaging of subcutaneous B16F10 melanoma and orthotopic A549 lung tumor. Taking advantages of a facile iodine exchange reaction, 125 I-labeled PThyN enables SPECT/CT imaging of tumors and monitoring of PThyN biodistribution in vivo. Besides, 131 I-labeled and cRGD-functionalized PThyN displays remarkable growth inhibition of the B16F10 tumor in mice (tumor inhibition rate > 89%). These poly(l-thyroxine) nanoparticles provide a unique and versatile theranostic platform for varying diseases.

A meta-analysis to examine whether nitrification inhibitors work through selectively inhibiting ammonia-oxidizing bacteria.

Nitrification inhibitor (NI) is often claimed to be efficient in mitigating nitrogen (N) losses from agricultural production systems by slowing down nitrification. Increasing evidence suggests that ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) have the genetic potential to produce nitrous oxide (N2O) and perform the first step of nitrification, but their contribution to N2O and nitrification remains unclear. Furthermore, both AOA and AOB are probably targets for NIs, but a quantitative synthesis is lacking to identify the "indicator microbe" as the best predictor of NI efficiency under different environmental conditions. In this present study, a meta-analysis to assess the response characteristics of AOB and AOA to NI application was conducted and the relationship between NI efficiency and the AOA and AOB amoA genes response under different conditions was evaluated. The dataset consisted of 48 papers (214 observations). This study showed that NIs on average reduced 58.1% of N2O emissions and increased 71.4% of soil NH 4 + concentrations, respectively. When 3, 4-dimethylpyrazole phosphate (DMPP) was applied with both organic and inorganic fertilizers in alkaline medium soils, it had higher efficacy of decreasing N2O emissions than in acidic soils. The abundance of AOB amoA genes was dramatically reduced by about 50% with NI application in most soil types. Decrease in N2O emissions with NI addition was significantly correlated with AOB changes (R 2 = 0.135, n = 110, P < 0.01) rather than changes in AOA, and there was an obvious correlation between the changes in NH 4 + concentration and AOB amoA gene abundance after NI application (R 2 = 0.037, n = 136, P = 0.014). The results indicated the principal role of AOB in nitrification, furthermore, AOB would be the best predictor of NI efficiency.

Brain delivery of Plk1 inhibitor via chimaeric polypeptide polymersomes for safe and superb treatment of orthotopic glioblastoma.

The chemotherapy toward glioblastoma (GBM) is severely challenged by blood-brain barrier and dose-limiting toxicity. Herein, we adopt brain delivery of Plk1 inhibitor volasertib (Vol), which is highly specific and presents low off-target toxicity, as a new means to treat GBM, for which angiopep-2-docked chimaeric polypeptide polymersome (ANG-CPP) was designed and prepared from poly(ethylene glycol)-b-poly(L-tyrosine)-b-poly(L-aspartic acid) for loading Vol to its watery interior via electrostatic interactions. ANG-CPP loaded with 13.9 wt% Vol (ANG-CPP-Vol) exhibited a small size of about 76 nm, superb colloidal stability (against dilution, serum and long-term storage), and enzyme-triggered drug release behavior (about 73% of Vol released within 8 h with proteinase K). In sharp contrast to free Vol, ANG-CPP-Vol induced complete G2/M cell cycle arrest in U-87 MG GBM cells giving 7.8-times better anti-tumor activity, prolonged circulation time and largely increased GBM enrichment. ANG-CPP-Vol effectively suppressed the growth of orthotopic U-87 MG GBM and significantly boosted mice survival rate. Importantly, ANG-CPP-Vol showed further reduced toxicity over free Vol. This great safety and remarkable efficacy of ANG-CPP-Vol renders it a high potential for treating GBM.

cRGD-decorated biodegradable polytyrosine nanoparticles for robust encapsulation and targeted delivery of doxorubicin to colorectal cancer in vivo.

The clinical success of nanomedicines demands on the development of simple biodegradable nanocarriers that can efficiently and stably encapsulate chemotherapeutics while quickly release the payloads into target cancer cells. Herein, we report that cRGD-decorated biodegradable polytyrosine nanoparticles (cRGD-PTN) boost encapsulation and targeted delivery of doxorubicin (DOX) to colorectal cancer in vivo. The co-assembly of poly(ethylene glycol)-poly(L-tyrosine) (PEG-PTyr) and cRGD-functionalized PEG-PTyr (mol/mol, 80/20) yielded small-sized cRGD-PTN of 70 nm. Interestingly, cRGD-PTN exhibited an ultra-high DOX encapsulation with drug loading contents ranging from 18.5 to 54.1 wt%. DOX-loaded cRGD-PTN (cRGD-PTN-DOX) was highly stable against dilution, serum, and Triton X-100 surfactant, while quickly released DOX in HCT-116 cancer cells, likely resulting from enzymatic degradation of PTyr. Flow cytometry, confocal microscopy and MTT assays displayed that cRGD-PTN-DOX was efficiently internalized into αvß5 overexpressing HCT-116 colorectal cancer cells, rapidly released DOX into the nuclei, and induced several folds better antitumor activity than non-targeted PTN-DOX and clinically used liposomal DOX (Lipo-DOX). SPECT/CT imaging revealed strong tumor accumulation of 125I-labeled cRGD-PTN, which was 2.8-fold higher than 125I-labeled PTN. Notably, cRGD-PTN-DOX exhibited over 5 times better toleration than Lipo-DOX and significantly more effective inhibition of HCT-116 colorectal tumor than non-targeted PTN-DOX control, affording markedly improved survival rate in HCT-116 tumor-bearing mice with depleting side effects at 6 or 12 mg DOX equiv./kg. cRGD-PTN-DOX with great simplicity, robust drug encapsulation and efficient nucleic drug release appears promising for targeted chemotherapy of colorectal tumor.