Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg−1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

Objectives

Up to now, little research has been focussed on discovering how zeta potential independently affects polymeric nanoparticle (NP) cytotoxicity.



Methods

Polymeric nanoparticles of gradient zeta potential ranging from −30 mv to +40 mv were fabricated using the same poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx) biopolymer. Interaction forces between nanoparticles and cells were measured by atomic force microscopy (AFM). Cytotoxicity of the nanoparticles to cells was investigated by using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay.



Results

Four kinds of nanoparticle with similar sizes and gradient zeta potentials, were fabricated. Those with positive surface charges were found to be more toxic than those with negative surface charges. Positively charged nanoparticles or nanoparticles with higher ‘like’ charges, offered higher interaction force with cells.



Conclusion

This work proposes a novel approach for investigating interaction between NPs and cells, and discloses the importance of controlling zeta potential in developing NPs-based formulations in the future.

Independent effect of polymeric nanoparticle zeta potential/surface charge, on their cytotoxicity and affinity to cells

With the development of many nanomedicines designed for tumor therapy, the diverse abilities of cerium oxide nanoparticles (CONPs) have encouraged researchers to pursue CONPs as a therapeutic agent to treat cancer. Research data have shown CONPs to be toxic to cancer cells, to inhibit invasion, and to sensitize cancer cells to radiation therapy and chemotherapy. CONPs also display minimal toxicity to normal tissues and provide protection from various forms of reactive oxygen species generation. Differential cytotoxicity is important for anticancer drugs to distinguish effectively between tumor cells and normal cells. The antioxidant capabilities of CONPs, which enable cancer therapy protection, have also resulted in the exploration of these particles as a potential anticancer treatment. Taken together, CONPs might be a potential nanomedicine for cancer therapy and this review highlights the current research into CONPs as a novel therapeutic for the treatment of cancer.

/pdf/cerium-oxide-nanoparticles-in-cancer-55nkgl7v61.pdf

Cerium oxide nanoparticles in cancer.

Nanomaterials have widely been used in the field of biological and biomedicine, such as tissue imaging, diagnosis and cancer therapy. In this study, we explored the cytotoxicity and photodynamic effect of different-sized ZnO nanoparticles to target cells. Our observations demonstrated that ZnO nanoparticles exerted dose-dependent and time-dependent cytotoxicity for cancer cells like hepatocellular carcinoma SMMC-7721 cells in vitro. Meanwhile, it was observed that UV irradiation could enhance the suppression ability of ZnO nanoparticles on cancer cells proliferation, and these effects were in the size-dependent manner. Furthermore, when ZnO nanoparticles combined with daunorubicin, the related cytotoxicity of anticancer agents on cancer cells was evidently enhanced, suggesting that ZnO nanoparticles could play an important role in drug delivery. This may offer the possibility of the great potential and promising applications of the ZnO nanoparticles in clinical and biomedical areas like photodynamic cancer therapy and others.

https://link.springer.com/content/pdf/10.1007%2Fs11671-010-9603-4.pdf

The Photodynamic Effect of Different Size ZnO Nanoparticles on Cancer Cell Proliferation In Vitro

Therapeutic proteins have attracted significant attention as they perform vital roles in various biological processes. The delivery of therapeutic proteins to target sites is, however, challenging due to their intrinsic sensitivity to different environmental conditions. Polymeric nanoparticles (NPs) can offer not only physical protection from environmental stimuli but also targeted delivery of such proteins to specific sites. In particular, NPs containing charged polymers are preferred for many applications as they provide gentle protection through electrostatic interactions. Moreover, most organs exhibit a specific pH, and by tuning the extent of the electrostatic interactions and contact duration between the target organ and polymeric NPs, the intracellular uptake of the latter and thus long-term therapeutic efficacy can be optimized. In this article, we will critically discuss the design considerations of charged polymeric NPs, strategies for and routes of protein delivery and how these are influenced depending on the choice of delivery route.

Polymer-based nanoparticles for protein delivery: design, strategies and applications

Erythropoietin-loaded oligochitosan nanoparticles for treatment of periventricular leukomalacia.

https://www.nature.com/articles/s41598-023-38367-4.pdf

MicroRNA-146a negatively regulates inflammation via the IRAK1/TRAF6/NF-κB signaling pathway in dry eye

In this study we prepared nanocarrier of erythropoietin (EPO) and the curative effect of the EPO-containing nanoparticles for periventricular leukomalacia (PVL) model was validated. It was demonstrated that EPO-containing nanoparticles can ameliorate drug-induced liquefaction caused by hypoxia. EPO-containing nanomedicine may open new therapeutic strategies in hypoxia cure.

Therapy for cerebral ischemic injury with erythropoietin-containing nanoparticles.

In some regions of the hippocampus, neurogenesis persists throughout life and is upregulated following hypoxia/ischemia. The mechanisms underlying the upregulation of neurogenesis, however, are not known. Here we examined the expression of two factors thought to be involved in hypoxia-related neurogenesis, hypoxia-inducible factor-1α (HIF-1α) and brain-derived erythropoietin (EPO), in the hippocampus of neonatal rats following hypoxia-ischemia. Sprague-Dawley rat pups were exposed to hypoxia-ischemia conditions or hypoxia conditions only. For the hypoxia-ischemia experiment, the left common carotid artery of Sprague-Dawley rat pups was ligated on postnatal day 7. The pups were exposed to hypoxic conditions and then returned to normoxia for re-oxygenation. Immunohistochemical staining was performed to evaluate EPO and HIF-1α expression at various time points after re-oxygenation (1 h, 6 h, 16 h, 1 d, 3 d, and 7 d). EPO expression in the hippocampus was verified using Western blot studies. For the hypoxia-only experiment, postnatal day 7 rat pups were continuously exposed to hypoxic conditions for different durations (0.5 h, 1 h, 2 h, 3 h, and 5 h). HIF-1α expression in the hippocampus was evaluated by immunohistochemical staining. In the hypoxia-ischemia group, EPO expression was significantly altered. The EPO expression increased during re-oxygenation, peaked at 16 h, and decreased thereafter. In the hypoxia-only group, the EPO protein was not detectable. When the rat pups were returned to normoxia for re-oxygenation, there was no HIF-1α expression. HIF-1α immunoreactivity was present in the hypoxia-only group and peaked in rats exposed to continuous hypoxic conditions for 3 h. In addition, endogenous EPO increased in the neonatal rats after the hypoxia-ischemia event. Furthermore, HIF-1α was induced as a result of hypoxia. We postulate that disruption of homeostasis triggers and enhances hippocampal neurogenesis. Thus, HIF-1α/EPO hypoxic signal transduction may initiate hippocampal neurogenesis following hypoxia-ischemia.

Hypoxia-inducible factor-1α and erythropoietin expression in the hippocampus of neonatal rats following hypoxia-ischemia.

Ischemic metabolism in the gut is a crucial issue of clinical concern for deep understanding of drug delivery. In this study we use nanochemistry in micelle to produce the nanocarrier of erythropoietin (EPO) and traced the metabolizable process of the EPO carrier in vivo. Nascence Sprague-Dawley rats of 5 days are treated with 50 IU/kg EPO nanocarriers. Curative effects of the EPO nanocarriers for periventricular leukomalacia (PVL) models are validated by the analysis of pathology and praxiology of the mice. We demonstrate in vivo that EPO nanocarriers can ameliorate drug-induced liquefaction caused by hypoxia. By tracking the metabolism of EPO in liver and kidney, we deduce that nanocarriers can effectively prolong the plasma half-life of EPO and slower clearance time compared to direct injection. Mobilization of late oligodendrocyte can be protected by treatment with EPO vehicle from hypoxia. Vehicle EPO may open new therapeutic strategies in hypoxia cure.

/pdf/erythropoietin-nanopariticles-therapy-for-cerebral-ischemic-3ug6uze5d2.pdf

Erythropoietin Nanopariticles: Therapy for Cerebral Ischemic Injury and Metabolize in Kidney and Liver

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