Yiming Niu

Targeted depletion of tumour-associated macrophages by an alendronate-glucomannan conjugate for cancer immunotherapy.

Tumour-associated macrophages (TAMs) are a set of macrophages residing in the tumour microenvironment. They play essential roles in mediating tumour angiogenesis, metastasis and immune evasion. Delivery of therapeutic agents to eliminate TAMs can be a promising strategy for cancer immunotherapy but an efficient vehicle to target these cells is still in pressing need. In this study, we developed a bisphosphonate-glucomannan conjugate that could efficiently target and specifically eliminate TAMs in the tumour microenvironment. We employed the polysaccharide from Bletilla striata (BSP), a glucomannan affinitive for macrophages that express abundant mannose receptors, to conjugate alendronate (ALN), a bisphosphonate compound with in vitro macrophage-inhibiting activities. In both in vitro and in vivo tests, the prepared ALN-BSP conjugate could preferentially accumulate in macrophages and induced them into apoptosis. In the subcutaneous S180 tumour-bearing mice model, the treatment using ALN-BSP effectively eliminated TAMs, remarkably inhibited angiogenesis, recovered local immune surveillance, and eventually suppressed tumour progression, without eliciting any unwanted effect such as systematic immune response. Interestingly, ALN alone failed to exhibit any anti-TAM activity in vivo, probably because this compound was susceptible to the mildly acidic tumour microenvironment. Taken together, these results demonstrate the potential of ALN-BSP as a safe and efficient tool targeted at direct depletion of TAMs for cancer immunotherapy.

Re-polarizing Myeloid-derived Suppressor Cells (MDSCs) with Cationic Polymers for Cancer Immunotherapy.

Our evolving understandings of cell-material interactions provide insights for using polymers to modulate cell behaviour that may lead to therapeutic applications. It is known that in certain cancers, myeloid-derived suppressor cells (MDSCs) play vital roles in promoting tumour progression, chiefly because of their ‘alternatively activated’ (or M2) phenotype that orchestrates immunosuppression. In this study, we demonstrated that two cationic polymers – cationic dextran (C-dextran) and polyethyleneimine (PEI) – could directly remodel these cells into an anti-tumour, ‘classically activated’ (or M1) phenotype, thereby stimulating these cells to express tumouricidal cytokines, reactivating the T cell functions, and prolonging the lifespan of the mice model. Our investigations with knock-out mice further indicate that the functions of these cationic polymers require the involvement of toll-like receptor 4-mediated signalling. Taken together, our study suggests that these cationic polymers can effectively and directly re-polarize MDSCs from an immunosuppressive characteristic to an anti-tumour phenotype, leading to successful restoration of immune surveillance in the tumour microenvironment and elimination of tumour cells. Our findings may have immediate impact on further development of polymer-based therapeutics for cancer immunotherapy.

Bioactive polysaccharides from natural resources including Chinese medicinal herbs on tissue repair

BackgroundFunctional polysaccharides can be derived from plants (including herbs), animals and microorganisms. They have been widely used in a broad of biomedical applications, such as immunoregulatory agents or drug delivery vehicles. In the past few years, increasing studies have started to develop natural polysaccharides-based biomaterials for various applications in tissue engineering and regenerative medicine.Main bodyWe discuss in this article the emerging applications of natural polysaccharides—particularly those derived from Chinese medicine—for wound healing. First, we introduce natural polysaccharides of three natural sources and their biological activities. Then, we focus on certain natural polysaccharides with growth factor-binding affinities and their inspired polymeric tools, with an emphasis on how these polysaccharides could possibly benefit wound healing. Finally, we report the latest progress in the discovery of polysaccharides from Chinese medicinal herbs with identified activities favouring tissue repair.ConclusionNatural polysaccharides with clearly elucidated compositions/structures, identified cellular activities, as well as desirable physical properties have shown the potential to serve as therapeutic tools for tissue regeneration.

Chameleonic Dye Adapts to Various Environments Shining on Macrocycles or Peptide and Polysaccharide Aggregates

This work describes latent fluorescence particles (LFPs) based on a new environmentally sensitive carbazole compound aggregated in water and their use as sensors for probing various cavitands and the different stages of aggregating systems. Cyclodextrins (CDs), cucurbit[n]urils (CB[n], n = 6, 7, 8), and a resorcinarene capsule were used to study the dynamic nature of the LFPs. The fluorescence was dramatically enhanced by a proposed disaggregation-induced emission enhancement (DIEE) mechanism with specific features for CB[n]. Then, the aggregated states of the dipeptides Leu-Leu, Phe-Phe, and Fmoc-Leu-Leu (vesicles, crystals, fibers) were studied by fluorescence spectroscopy and confocal fluorescence microscopy thanks to the adaptive and emissive behavior of the LFPs, allowing us to study an interesting polymorphism phenomenon. The LFPs have then been used in the sensing of the aggregation of the polysaccharide alginate, for which distinct fluorescence turn-on is detected upon stepwise biopolymer assembly, and for amylose detection. The carbazole particles not only adapt to various environments but also display multicolor fluorescent signals. They can be used for the fast probing of the aggregation propensity of newly prepared molecules or biologically relevant compounds or to accelerate the discovery of new macrocycles or of self-assembling peptides in water.

APTES-modified nanosilica -- but neither APTES nor nanosilica -- inhibits endothelial cell growth via arrest of cell cycle at G1 phase:

The adverse effects of nanomaterials on the living system have attracted considerable attention in the past few years. Such effects may come from either the core nanomaterials or the chemical agents used to modify the nanomaterials – the latter being largely overlooked. In a free form, these modifying agents might have little impact on living cells; however, they may exhibit distinct biological effects when they assemble into a larger dimension. Here, we report that (3-aminopropyl)triethoxysilane – a small molecule compound ubiquitously employed to functionalise nanosilica surface – could decrease the viability of human umbilical vein endothelial cells when it was grafted onto the nanosilica surface. However, intriguingly, such effect was not found in 3-aminopropyl)triethoxysilane itself, the unmodified silica nanoparticles or the 3-aminopropyl)triethoxysilane-modified microparticles. Change of surface charge was excluded as a cause and apoptosis was not observed. Nevertheless, the 3-aminopropyl)triethoxysilane-modified nanoparticles could exclusively arrest cell cycle at G1 phase. Our findings suggest that substances could gain ‘new’ functions at the nanoscale, which may not be found in their larger or smaller counterparts. Understanding of such effects will provide critical insights for better evaluation and thus safer use of nanomaterials, in particular those having been pre-modified with other agents.