With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels.

Macroautophagy/autophagy is a cellular process in which cytosolic contents are degraded by lysosome in response to various stress conditions. Apart from its role in the maintenance of cellular homeostasis, autophagy also involves in regulation of cell cycle progression under nutrient-deprivation conditions. However, whether and how autophagy is regulated by the cell cycle especially during mitosis remains largely undefined. Here we show that WIPI2/ATG18B (WD repeat domain, phosphoinositide interacting 2), an autophagy-related (ATG) protein that plays a critical role in autophagosome biogenesis, is a direct substrate of CUL4-RING ubiquitin ligases (CRL4s). Upon mitosis induction, CRL4s are activated via neddylation, and recruit WIPI2 via DDB1 (damage specific DNA binding protein 1), leading to polyubiquitination and proteasomal degradation of WIPI2 and suppression of autophagy. The WIPI2 protein level and autophagy during mitosis could be rescued by knockdown of CRL4s or treatment with MLN4924/Pevonedistat, a selective inhibitor of CRLs, via suppression of NAE1 (NEDD8 activating enzyme E1 subunit 1). Moreover, restoration of WIPI2 rescues autophagy during mitosis and leads to mitotic slippage and cell senescence. Our study thus discovers a novel function of CRL4s in autophagy by targeting WIPI2 for polyubiquitination and proteasomal degradation during mitosis.Abbreviations: ACTB, actin beta; ATG, autophagy-related; AMPK, AMP-activated protein kinase; AURKB/ ARK2, aurora kinase B; BafA1, bafilomycin A 1 ; CCNB1, cyclin B1; CDK1, cyclin dependent kinase 1; CHX, cycloheximide; CQ, chloroquine; CRL4s, CUL4-RING ubiquitin ligases; DDB1, damage specific DNA binding protein 1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP, green fluorescent protein; GST, glutathione S-transferase; MAP1LC3B/LC3B, microtubule associated protein 1 light chain 3 beta; STK11/ LKB1,serine/threonine kinase 11; MTORC1/MTOR complex 1, mechanistic target of rapamycin kinase complex 1; NAE1, NEDD8 activating enzyme E1 subunit 1; NOC, nocodazole; RING, really interesting new gene; RBX1, ring-box 1; SA-GLB1/β-gal, senescence-associated galactosidase beta 1; TSC2, TSC complex subunit 2; TUBA, tubulin alpha; WIPI2, WD repeat domain, phosphoinositide interacting 2 ARTICLE HISTORY

A novel small-diameter graft consisting of nanofibrous bacterial cellulose and submicrofibrous cellulose acetate was prepared and evaluated in vitro and in vivo.

Growing experience with engineered chimeric antigen receptor (CAR)‐T cells has revealed some of the challenges associated with developing patient‐specific therapy. The promising clinical results obtained with CAR‐T therapy nevertheless demonstrate the urgency of advancements to promote and expand its uses. There is indeed a need to devise novel methods to generate potent CARs, and to confer them and track their anti‐tumor efficacy in CAR‐T therapy. A potentially effective approach to improve the efficacy of CAR‐T cell therapy would be to exploit the benefits of nanotechnology. This report highlights the current limitations of CAR‐T immunotherapy and pinpoints potential opportunities and tremendous advantages of using nanotechnology to 1) introduce CAR transgene cassettes into primary T cells, 2) stimulate T cell expansion and persistence, 3) improve T cell trafficking, 4) stimulate the intrinsic T cell activity, 5) reprogram the immunosuppressive cellular and vascular microenvironments, and 6) monitor the therapeutic efficacy of CAR‐T cell therapy. Therefore, genetic and functional modifications promoted by nanotechnology enable the generation of robust CAR‐T cell therapy and offer precision treatments against cancer.

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