Polydopamine nanoparticles coated with a metal-polyphenol network for enhanced photothermal/chemodynamic cancer combination therapy.

Polydopamine nanoparticles (PDA NPs) are commonly used for photothermal therapy (PTT) of cancer because of their good biocompatibility and photothermal conversion capability. However, it is difficult to achieve a good tumor inhibition effect with a single PTT of PDA. Therefore, in this work, we prepared a combined anticancer nanosystem for enhanced chemodynamic therapy (CDT)/PTT by coating PDAs with an (-)-epigallocatechin gallate (EGCG)/iron (Fe) metal-polyphenol network (MPN). The MPN shell of this nanosystem named EGCG@PDA is degraded by the weakly acidic environment intracellular, releasing EGCG and Fe3+. EGCG inhibits the expression of heat shock proteins (HSPs) in cancer cells, thus eliminating their thermal protection against cancer cells for enhanced PTT. Meanwhile, the reductive EGCG can also reduce Fe3+ to Fe2+, to catalyze the decomposition of overexpressed hydrogen peroxide (H2O2) in cancer cells to generate strong oxidative hydroxyl radicals (OH), i.e., catalyzing the Fenton reaction, for CDT. After the Fenton reaction, the re-oxidized Fe ions can be reduced again by EGCG and reused to catalyze the Fenton reaction, which can achieve enhanced CDT. Both in vitro and in vivo studies have shown that EGCG@PDA has low dark toxicity and good anticancer effects. It is expected to be used for precision cancer therapy.

Small-size Ti3C2Tx MXene nanosheets coated with metal-polyphenol nanodots for enhanced cancer photothermal therapy and anti-inflammation.

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size Ti3C2Tx MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size Ti3C2Tx MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.

Characterizing microRNAs and their targets in different organs of Camellia sinensis var. assamica.

To comprehensively annotate miRNAs and their targets in tea plant, Camellia sinensis, we sequenced small and messenger RNAs of 9 samples of Camellia sinensis var. assamica (YK-10), a diploid elite cultivar widely grown in southwest China. In order to identify targets of miRNAs, we sequenced two degradome sequencing profiles from leaves and roots of YK-10, respectively. By analyzing the small RNA-Seq profiles, we newly identified 137 conserved miRNAs and 23 species specific miRNAs in the genome of YK-10, which significantly improved the annotation of miRNAs in tea plant. Approximately 2000 differently expressed genes were identified when comparing RNA-Seq profiles of any two of the three organs selected in the study. Totally, more than 5000 targets of conserved miRNAs were identified in the two degradome profiles. Furthermore, our results suggest that a few miRNAs play roles in the biosynthesis pathways of theanine, caffeine and flavonoid. These results enhance our understanding of small RNA guided gene regulations in different organs of tea plant.

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability.

Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We have identified two nanoparticle formulations incorporating kaempferol that may lead to breakthroughs in cancer treatment. Both PEO-PPO-PEO and PLGA nanoparticle formulations had superior effects compared with kaempferol alone in reducing cancer cell viability.