Kan Liu

Finding a needle in a haystack: A new technology is demonstrated to enrich circulating tumor cells (CTCs) with high efficiency by integrating an antibody-coated silicon nanopillar (SiNP, see picture; gray) substrate with an overlaid polydimethylsiloxane (PDMS) microfluidic chaotic mixer (turquoise). It shows significantly improved sensitivity in detecting rare CTCs from whole blood, thus providing an alternative for monitoring cancer progression. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN's biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.

A nanostructured platform that combines electrospun TiO2 nanofibers (TiNFs)-deposited substrate and cell-capture agent realizes significant capture of circulating tumor cells (CTCs). The enhanced local topographic interactions between the horizontally packed TiNFs deposited substrates and extracellular matrix scaffolds, in addition to anti-EpCAM/EpCAM biological recognition, contributes to the significantly enhanced capture efficiency compared to flat surfaces. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism "anastasis" (Greek for "rising to life"). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity.

In this paper we describe a novel method of manufacturing shape-controlled calcium alginate gel microparticles in a microfluidic device. Both manufacturing shape-controlled microparticles and synthesizing hydrogel microparticles could be performed simultaneously in the microfluidic device. The novel microfluidic device comprised of two individual flow-focusing channels and a synthesizing channel was successfully applied as a continuous microfluidic reactor to synthesize gel microparticles with size and shape control. By passive control based on the microchannel geometric confinement and liquid-phase flow rates, we succeeded in producing monodisperse sodium alginate microparticles with diverse shapes (such as plugs, disks, microspheres, rods, and threads) in the flow-focusing channels of the microfluidic device. The shape and size of the sodium alginate microparticles could be tuned by adjusting the flow rates of the various streams. Further stages of the chemical reaction could be initiated by mixing sodium alginate microparticles and calcium chloride (CaCl2) solution in the synthesizing channel. The shapes of the sodium alginate microparticles could be permanently preserved by the synthesis of calcium alginate gel microparticles. The preparation conditions of size- and shape-controlled calcium alginate microparticles and influence factors were studied.