Chemically Engineered Porous Molecular Coatings as Reactive Oxygen Species Generators and Reservoirs for Long-Lasting Self-Cleaning Textiles.

Wearable personal protective equipment that is decorated with photoactive self-cleaning materials capable of actively neutralizing biological pathogens is in high demand. Here, we developed a series of solution-processable, crystalline porous materials capable of addressing this challenge. Textiles coated with these materials exhibit a broad range of functionalities, including spontaneous reactive oxygen species (ROS) generation upon absorption of daylight, and long-term ROS storage in dark conditions. The ROS generation and storage abilities of these materials can be further improved through chemical engineering of the precursors without altering the three-dimensional assembled superstructures. In comparison with traditional TiO2 or C3 N4 self-cleaning materials, the fluorinated molecular coating material HOF-101-F shows a 10- to 60-fold enhancement of ROS generation and 10- to 20-fold greater ROS storage ability. Our results pave the way for further developing self-cleaning textile coatings for the rapid deactivation of highly infectious pathogenic bacteria under both daylight and light-free conditions.

Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive shell crosslinked micelles loading disulfiram.

Metastasis, the main cause of cancer related deaths, remains the greatest challenge in cancer treatment. Disulfiram (DSF), which has multi-targeted anti-tumor activity, was encapsulated into redox-sensitive shell crosslinked micelles to achieve intracellular targeted delivery and finally inhibit tumor growth and metastasis. The crosslinked micelles demonstrated good stability in circulation and specifically released DSF under a reductive environment that mimicked the intracellular conditions of tumor cells. As a result, the DSF-loaded redox-sensitive shell crosslinked micelles (DCMs) dramatically inhibited cell proliferation, induced cell apoptosis and suppressed cell invasion, as well as impairing tube formation of HMEC-1 cells. In addition, the DCMs could accumulate in tumor tissue and stay there for a long time, thereby causing significant inhibition of 4T1 tumor growth and marked prevention in lung metastasis of 4T1 tumors. These results suggested that DCMs could be a promising delivery system in inhibiting the growth and metastasis of breast cancer.

Low molecular weight polyethylenimine-graft-Tween 85 for effective gene delivery: synthesis and in vitro characteristics.

The development of safe and efficient gene delivery systems is still a challenge for successful gene therapy. In this work, low molecular weight polyethylenimine (PEI 2K) was modified by Tween 85, which bears three oleate chains. Tween 85 modified PEI 2K (TP) could condense DNA efficiently, and TP/DNA complexes (TPCs) showed high resistance to salt-induced aggregation and enzymatic degradation. In addition, TP did not show the obvious cytotoxicity. The introduction of Tween 85 led to a significant increase in the cellular uptake of complexes with higher transfection efficiency, which was strongly inhibited by the addition of free Tween 85 in MCF-7/ADR cells, but not in MCF-7 cells. These results indicated that TP could be a potentially safe and effective copolymer for gene delivery, and TPCs could be taken up mainly by Tween 85-mediated endocytosis in MCF-7/ADR cells.

Effective delivery of p65 shRNA by optimized Tween 85-polyethyleneimine conjugate for inhibition of tumor growth and lymphatic metastasis.

To maximize the interference efficacy of pGPU6/Neo-p65 shRNA-expressing pDNA (p65 shRNA) and subsequently more effectively inhibit tumor growth and lymphatic metastasis through blocking the nuclear factor-kappa B (NF-κB) signaling pathway, seven Tween 85-polyethyleneimine (PEI) conjugates (TnPs, n=2, 3, 4, 5, 6, 7 and 8), which differed in the length of the polymethylene [-(CH2)n-] spacer between Tween 85 and PEI, were synthesized and investigated. The results showed that the transfection efficiency and cytotoxicity both increased with the spacer chain length. Then, TnPs with a [-(CH2)6-] spacer (T6P) were chosen to deliver p65 shRNA to a tumor and subsequently inhibit tumor growth and lymphatic metastasis. The T6P/p65 shRNA complex nanoparticles (T6Ns) could significantly down-regulate p65 expression in breast cancer cells, and consequently inhibit cell invasion and disrupt the tube formation. Most importantly, T6Ns accumulated greatly in tumor tissue, and as a result, significantly inhibited the growth and lymphatic metastasis of breast cancer xenograft. All these results indicated that the transfection efficacies of cationic amphiphiles could be significantly modulated by minor structural variations, and that T6P was promising for the effective delivery of p65 shRNA to knock down the expression of the key metastasis-driving genes and inhibit tumor growth and metastasis.

Smart pH-sensitive and temporal-controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram.

The combination of a chemotherapeutic drug with a multidrug resistance (MDR) modulator has emerged as a promising strategy for treating MDR cancer. To ensure two drugs could be simultaneously delivered to tumor region at the optimum ratio, and the MDR modulator could be released earlier and faster than the chemotherapeutic drug to inactivate P-glycoprotein (P-gp) and subsequently inhibit the pumping out of the chemotherapeutic drug, a smart pH-sensitive polymeric micelles system with high drug loading and precise drug ratio was designed and prepared by conjugating doxorubicin (DOX) to poly(styrene-co-maleic anhydride) (SMA) derivative with adipic dihydrazide (ADH) through a acid-cleavable hydrazone bond, and then encapsulating disulfiram (DSF), a P-gp inhibitor as well as an apoptosis inducer, into the micelles formed by the self-assembly of SMA-ADH-DOX (SAD) conjugate. The pH-sensitive polymeric micelles system enabled a temporal release of two drugs: encapsulated DSF was released fast to inhibit the activity of P-gp and restore cell apoptotic signaling pathways, while conjugated DOX was released in a sustained and pH-dependent manner and highly accumulated in drug resistant cells to exert therapeutic effect, due to the inactivation of P-gp by DSF. The smart co-delivery system was very effective in enhancing the cytotoxicity by increasing the intracellular accumulation of DOX and promoting the apoptotic response, and showed the most effective inhibitory effect on the growth of drug-resistant breast cancer xenografts as compared to other combinations of both drugs. In a word, this smart co-delivery system has significant promise for the clinical therapy of MDR cancer.

The inhibition of metastasis and growth of breast cancer by blocking the NF-κB signaling pathway using bioreducible PEI-based/p65 shRNA complex nanoparticles.

Metastasis is one of the greatest challenges in cancer treatment. In this study, a bioreducible polymer, Tween 85-s-s-polyethyleneimine 2K (TSP), was synthesized and used as a non-viral gene vector for p65 shRNA to block NF-κB signaling pathway, thereby inhibiting the growth and metastasis of breast cancer. The TSP/p65 shRNA complex nanoparticles (TSNs) could significantly down-regulate p65 expression in breast cancer cells due to the rapid degradation of TSP with prompt shRNA release, and consequently not only inhibit cell proliferation and invasion, but also induce cell apoptosis and disrupt the tube formation. Most importantly, TSNs showed high accumulation in tumor and almost completely inhibited the growth and metastasis of the breast cancer xenograft in nude mice induced by MDA-MB-435 cells. All these results indicated the promising of TSP as a non-viral gene vector to knock down p65 expression and inhibit the growth and metastasis of breast cancer.

Amphiphilic graft copolymer based on poly(styrene-co-maleic anhydride) with low molecular weight polyethylenimine for efficient gene delivery.

BACKGROUND AND METHODS: A new amphiphilic comb-shaped copolymer (SP) was synthesized by conjugating poly(styrene-co-maleic anhydride) with low molecular weight polyethyleneimine for gene delivery. Fourier transform infrared spectrum, (1)H nuclear magnetic resonance, and gel permeation chromatography were used to characterize the graft copolymer. RESULTS: The buffering capability of SP was similar to that of polyethyleneimine within the endosomal pH range. The copolymer could condense DNA effectively to form complexes with a positive charge (13-30 mV) and a small particle size (130-200 nm) at N/P ratios between 5 and 20, and protect DNA from degradation by DNase I. In addition, SP showed much lower cytotoxicity than polyethyleneimine 25,000. Importantly, the gene transfection activity and cellular uptake of SP-DNA complexes were all markedly higher than that of complexes of polyethyleneimine 25,000 and DNA in MCF-7 and MCF-7/ADR cell lines. CONCLUSION: This work highlights the promise of SP as a safe and efficient synthetic vector for DNA delivery.