Radioactive hybrid semiconducting polymer nanoparticles for imaging-guided tri-modal therapy of breast cancer.

Due to the rapid progression and aggressive metastasis of breast cancer, its diagnosis and treatment remain a great challenge. The simultaneous inhibition of tumor growth and metastasis is necessary for breast cancer to obtain ideal therapeutic outcomes. We herein report the development of radioactive hybrid semiconducting polymer nanoparticles (SPNH) for imaging-guided tri-modal therapy of breast cancer. Two semiconducting polymers are used to form SPNH with a diameter of around 60 nm via nano-coprecipitation and they are also labeled with iodine-131 (131I) to enhance the imaging functions. The formed SPNH show good radiolabeling stability and excellent photodynamic and photothermal effects under 808 nm laser irradiation to produce singlet oxygen (1O2) and heat. Moreover, SPNH can generate 1O2 with ultrasound irradiation via their sonodynamic properties. After intravenous tail vein injection, SPNH can effectively accumulate in the subcutaneous 4T1 tumors of living mice as verified via fluorescence and single photon emission computed tomography (SPECT) imaging. With the irradiation of tumors using an 808 nm laser and US, SPNH mediate photodynamic therapy (PDT), photothermal therapy (PTT) and sonodynamic therapy (SDT) to kill tumor cells. Such a tri-modal therapy leads to an improved efficacy in inhibiting tumor growth and suppressing tumor metastasis compared to the sole SDT and combinational PDT-PTT. This study thus demonstrates the applications of SPNH to diagnose tumors and combine different therapies for effective breast cancer treatment.

Directed assembly of genetically engineered eukaryotic cells into living functional materials via ultrahigh-affinity protein interactions.

Engineered living materials (ELMs) are gaining traction among synthetic biologists, as their emergent properties and nonequilibrium thermodynamics make them markedly different from traditional materials. However, the aspiration to directly use living cells as building blocks to create higher-order structures or materials, with no need for chemical modification, remains elusive to synthetic biologists. Here, we report a strategy that enables the assembly of engineered Saccharomyces cerevisiae into self-propagating ELMs via ultrahigh-affinity protein/protein interactions. These yeast cells have been genetically engineered to display the protein pairs SpyTag/SpyCatcher or CL7/Im7 on their surfaces, which enable their assembly into multicellular structures capable of further growth and proliferation. The assembly process can be controlled precisely via optical tweezers or microfluidics. Moreover, incorporation of functional motifs such as super uranyl-binding protein and mussel foot proteins via genetic programming rendered these materials suitable for uranium extraction from seawater and bioadhesion, respectively, pointing to their potential in chemical separation and biomedical applications.

An Efficient Closed Form Solution to the Absolute Orientation Problem for Camera with Unknown Focal Length.

In this paper we propose an efficient closed form solution to the absolute orientation problem for cameras with an unknown focal length, from two 2D-3D point correspondences and the camera position. The problem can be decomposed into two simple sub-problems and can be solved with angle constraints. A polynomial equation of one variable is solved to determine the focal length, and then a geometric approach is used to determine the absolute orientation. The geometric derivations are easy to understand and significantly improve performance. Rewriting the camera model with the known camera position leads to a simpler and more efficient closed form solution, and this gives a single solution, without the multi-solution phenomena of perspective-three-point (P3P) solvers. Experimental results demonstrated that our proposed method has a better performance in terms of numerical stability, noise sensitivity, and computational speed, with synthetic data and real images.

Characterization of Single-Cell Osmotic Swelling Dynamics for New Physical Biomarkers.

Characterization of cell physical biomarkers is vital to understand cell properties and applicable for disease diagnostics. Current methods used to analyze physical phenotypes involve external forces to deform the cells. Alternatively, internal tension forces via osmotic swelling can also deform the cells. However, an established assumption contends that the forces generated during hypotonic swelling concentrated on the plasma membrane are incapable of assessing the physical properties of nucleated cells. Here, we utilized an osmotic swelling approach to characterize different types of nucleated cells. Using a microfluidic device for cell trapping arrays with truncated hanging micropillars (CellHangars), we isolated single cells and evaluated the swelling dynamics during the hypotonic challenge at 1 s time resolution. We demonstrated that cells with different mechanical phenotypes showed unique swelling dynamics signature. Different types of cells can be classified with an accuracy of up to ∼99%. We also showed that swelling dynamics can detect cellular mechanical property changes due to cytoskeleton disruption. Considering its simplicity, swelling dynamics offers an invaluable label-free physical biomarker for cells with potential applications in both biological studies and clinical practice.

Gradual ghost imaging of moving objects by tracking based on cross correlation.

The requirement of a large number of samplings limits the performance of ghost imaging for moving objects. Conventionally, tracking and imaging of the moving objects are done independently; thus, sequential clear images of the moving target during its evolution are required. In this Letter, we propose to obtain the displacement of the object via cross correlation between sequential unclear rough images. Then, a high-quality image of the moving object can be reconstructed gradually during its evolution. Our method works well for translating and rotating objects.

Tracking and imaging of moving objects with temporal intensity difference correlation.

At present, a large number of samplings are required to reconstruct an image of the objects in ghost imaging. When imaging moving objects, it will be hard to perform enough samplings during the moment when the objects can be taken as immobile, causing the reconstructed image of the objects deteriorating. In this paper, we propose a temporal intensity difference correlation ghost imaging scheme, in which a high-quality image of the moving objects within a complex scene can be extracted with much fewer samplings. The spatial sparsity of the moving objects is utilized, while only a linear algorithm is required. This method decreases the number of required samplings, thus relaxing the requirement on high refresh frequency of illumination source and high speed detector, to obtain the information of moving objects with ghost imaging.

Ghost imaging normalized by second-order coherence.

Towards improvements in the quality of reconstructed images, the errors in the point spread function of a ghost imaging system caused by a limited number of samplings and imperfect illumination are discussed. We propose an algorithm by normalizing with the second-order coherence of the illumination field, with which the errors caused by imperfect illumination can be reduced, such as non-uniform spatial distribution of the average intensity, spatially varying profile of the second-order degree of coherence, or power fluctuation.

Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization.

There is a clinical need for new, more effective treatments for chronic wounds in diabetic patients. Lack of epithelial cell migration is a hallmark of nonhealing wounds, and diabetes often involves endothelial dysfunction. Therefore, targeting re-epithelialization, which mainly involves keratinocytes, may improve therapeutic outcomes of current treatments. In this study, we present an integrin-binding prosurvival peptide derived from angiopoietin-1, QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine), as a therapeutic candidate for diabetic wound treatments by demonstrating its efficacy in promoting the attachment, survival, and collective migration of human primary keratinocytes and the activation of protein kinase B Akt and MAPKp42/44 The QHREDGS peptide, both as a soluble supplement and when immobilized in a substrate, protected keratinocytes against hydrogen peroxide stress in a dose-dependent manner. Collective migration of both normal and diabetic human keratinocytes was promoted on chitosan-collagen films with the immobilized QHREDGS peptide. The clinical relevance was demonstrated further by assessing the chitosan-collagen hydrogel with immobilized QHREDGS in full-thickness excisional wounds in a db/db diabetic mouse model; QHREDGS showed significantly accelerated and enhanced wound closure compared with a clinically approved collagen wound dressing, peptide-free hydrogel, or blank wound controls. The accelerated wound closure resulted primarily from faster re-epithelialization and increased formation of granulation tissue. There were no observable differences in blood vessel density or size within the wound; however, the total number of blood vessels was greater in the peptide-hydrogel-treated wounds. Together, these findings indicate that QHREDGS is a promising candidate for wound-healing interventions that enhance re-epithelialization and the formation of granulation tissue.