The integrated lipopeptide (RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment. After self-assembling and target coating modification, the poly... Show moreThe integrated lipopeptide (RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment. After self-assembling and target coating modification, the poly(gamma-glutamic acid) (gamma-PGA)/RVA nano-vectors can sequentially respond to pH & redox stimuli, and guarantee efficient therapeutic gene delivery and control release of all -trans retinoic acid. The design provides a facile but promising strategy to treat refractory cancers.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Show less
Capelôa, L.; Yazdi, M.; Zhang, H.; Chen, X.; Nie, Y.; Wagner, E.; ... ; Barz, M. 2021
ABC-type triblock copolymers are a rising platform especially for oligonucleotide delivery as they offer an additional functionality besides the anyhow needed functions of shielding and... Show moreABC-type triblock copolymers are a rising platform especially for oligonucleotide delivery as they offer an additional functionality besides the anyhow needed functions of shielding and complexation. The authors present a polypept(o)ide-based triblock copolymer synthesized by amine-initiated ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs), comprising a shielding block A of polysarcosine (pSar), a poly(S-ethylsulfonyl-l-cystein) (pCys(SO2 Et)) block B for bioreversible and chemo-selective cross-linking and a poly(l-lysine) (pLys) block C for complexation to construct polyion complex (PIC) micelles as vehicle for small interfering RNA (siRNA) delivery. The self-assembly behavior of ABC-type triblocks is investigated to derive correlations between block lengths of the polymer and PIC micelle structure, showing an enormous effect of the β-sheet forming pCys(SO2 Et) block. Moreover, the block enables the introduction of disulfide cross-links by reaction with multifunctional thiols to increase stability against dilution. The right content of the additional block leads to well-defined cross-linked 50-60 nm PIC micelles purified from production impurities and determinable siRNA loading. These PIC micelles can deliver functional siRNA into Neuro2A and KB cells evaluated by cellular uptake and specific gene knockdown assays. Show less
Chen, X.; Jin, R.; Jiang, Q.; Bi, Q.; He, T.; Song, X.; ... ; Nie, Y. 2021
The tumor hypoxic microenvironment not only induces genetic and epigenetic changes in tumor cells, immature vessels formation for oxygen demand, but also compromises the efficiency of therapeutic... Show moreThe tumor hypoxic microenvironment not only induces genetic and epigenetic changes in tumor cells, immature vessels formation for oxygen demand, but also compromises the efficiency of therapeutic interventions. On the other hand, conventional therapeutic approaches which kill tumor cells or destroy tumor blood vessels to block nutrition and oxygen supply usually facilitate even harsher microenvironment. Thus, simultaneously relieving the strained response of tumor cells and blood vessels represents a promising strategy to reverse the adverse tumor hypoxic microenvironment. In the present study, an integrated amphiphilic system (RSCD) is designed based on Angiotensin II receptor blocker candesartan for siRNA delivery against the hypoxia-inducible factor-1 alpha (HIF-1α), aiming at both vascular and cellular "relaxation" to reconstruct a tumor normoxic microenvironment. Both in vitro and in vivo studies have confirmed that the hypoxia-inducible HIF-1α expression is down-regulated by 70% and vascular growth is inhibited by 60%. The "relaxation" therapy enables neovascularization with more complete and organized structures to obviously increase the oxygen level inside tumor, which results in a 50% growth inhibition. Moreover, reconstruction of tumor microenvironment enhances tumor-targeted drug delivery, and significantly improves the chemotherapeutic and photodynamic anticancer treatments. Show less
Liang, H.; Bi, Q.J.; Hu, A.; Chen, X.B.; Jin, R.R.; Song, X.; ... ; Nie, Y. 2020
A novel platform rationally integrating indocyanine green analogues and an arginine-rich dendritic peptide with both nitroreductase (NTR) and glutathione (GSH) reduction responsive linkers was... Show moreA novel platform rationally integrating indocyanine green analogues and an arginine-rich dendritic peptide with both nitroreductase (NTR) and glutathione (GSH) reduction responsive linkers was developed. This multifunctional platform can enable selective and efficient gene delivery and specific turn-on fluorescence imaging in tumors. Show less
Liang, H.; Chen, X.B.; Jin, R.R.; Ke, B.W.; Barz, M.; Ai, H.; Nie, Y. 2020
Codelivery of diagnostic probes and therapeutic molecules often suffers from intrinsic complexity and premature leakage from or degradation of the nanocarrier. Inspired by the "Y" shape of... Show moreCodelivery of diagnostic probes and therapeutic molecules often suffers from intrinsic complexity and premature leakage from or degradation of the nanocarrier. Inspired by the "Y" shape of indocyanine green (ICG), the dye is integrated in an amphiphilic lipopeptide (RNF). The hydrophilic segment is composed of arginine-rich dendritic peptides, while cyanine dyes are modified with two long carbon chains and employed as the hydrophobic moiety. They are linked through a disulfide linkage to improve the responsivity in the tumor microenvironment. After formulation with other lipopeptides at an optimized ratio, the theranostic system (RNS-2) forms lipid-based nanoparticles with slight positive zeta potential enabling efficient condensation of DNA. The RNS-2 displays glutathione responded gene release, activatable fluorescence recovery, and up to sevenfold higher in vitro transfection than Lipofectamine 2000. Compared with a Cy3 and Cy5 labeled fluorescence resonance energy transfer indicator for gene release, the "turn-on" indocyanine green analogs exhibit longer emission wavelength and better positive correlation with the dynamic processes of gene delivery. More importantly, the RNS-2 system enables efficient near infrared imaging guided gene transfer in tumor-bearing mice and thus provides more precise and accurate information on location of the cargo gene and synthesized carriers. Show less
My research includes both qualitative and quantitative analyses of the public discourse in Chinese online media platforms. Throughout my research, I have incorporated a variety of digital tools for... Show moreMy research includes both qualitative and quantitative analyses of the public discourse in Chinese online media platforms. Throughout my research, I have incorporated a variety of digital tools for data analysis. My study of China’s geopolitical strategy with respect to the current Belt and Road Initiative and its challenges ahead is to understand how digital media are shaping the communicative strategies of the traditional mass media in contemporary China. By examining the intertwined relations among traditional mass media, social media platforms, China’s cultural governance and policy-making mechanisms, my research also expands our understanding of how the advances of the ICTs influence the government’s communicative strategies. Show less
