Combined Phycocyanin and Hematoporphyrin Monomethyl Ether for Breast Cancer Treatment via Photosensitizers Modified Fe3O4 Nanoparticles Inhibiting the Proliferation and Migration of MCF-7 Cells.

Photodynamic therapy (PDT), combining the laser and photosensitizers to kill tumor cells, has the potential to address many current medical requirements. In this study, magnetic Fe3O4 nanoparticles were first employed as cores and modified with oleic acid (OA) and 3-triethoxysilyl-1-propanamine. Then, the photosensitizers phycocyanin (PC) and hematoporphyrin monomethyl ether (HMME), which might be able to stimulate the cell release of reactive oxygen species after the irradiation of a near-infrared (NIR) laser, were grafted on the surface of such nanoparticles. Our results revealed the high-efficiency inhibition of breast cancer MCF-7 cells growing upon near-infrared irradiation both in vitro and in vivo. Furthermore, it was the synergy between the natural photosensitizers PC and the synthetic photosensitizers HMME that deeply influenced such inhibition compared to the groups that used either of these medicines alone. To utilize the combination of different photosensitive agents, our study thus provides a new strategy for breast cancer treatment.

Focused ultrasound-mediated cerium-based nanoreactor against Parkinson's disease via ROS regulation and microglia polarization.

Neuronal damage caused by oxidative stress and inflammatory microenvironment dominated by microglia are the main obstacles in the treatment of Parkinson's disease (PD). In this study, we developed an integrated nanoreactor Q@CeBG by encapsulating CeO2 nanozyme and quercetin (Que) into glutathione-modified bovine serum albumin, and then selected focused ultrasound (FUS) to temporarily open the blood-brain barrier (BBB) to enhance the accumulation level of Q@CeBG in the brain. Q@CeBG exhibited superior multi-ROS scavenging activity. Under the assistance of FUS, Q@CeBG nanoreactor can penetrate the BBB and act on neurons as well as microglia, reducing the neuron's oxidative stress level and polarizing microglia's phenotype from proinflammatory M1 to anti-inflammatory M2. In vitro and In vivo experiments demonstrated that Q@CeBG nanoreactor with good biocompatibility exhibit outstanding neuroprotection and immunomodulatory effects. In short, this dual synergetic nanoreactor will become a reliable platform against PD.

Natural Phycocyanin/Paclitaxel Micelle Delivery of Therapeutic P53 to Activate Apoptosis for HER2 or ER Positive Breast Cancer Therapy.

The P53 gene is commonly mutated in breast cancer, protein based the gene as anticancer drugs could provide efficient and stable advantages by restoring the function of the wild-type P53 protein. In this study, we describe the creation and utilization of a micelle composed by natural phycocyanin and paclitaxel and grafting anti-HER2 (PPH), which effectively packages and transports recombinant P53 protein with anti-ER (PE), resulting in a new entity designated as PE@PPH, to address localization obstacles and modify cellular tropism to the cell membrane or nucleus. The results indicate that PE@PPH has strong antitumor properties, even at low doses of PTX both in vitro and in vivo. These findings suggest that PE@PPH could be an enhancing micelle for delivering therapeutic proteins and promoting protein functional recovery, particularly in addressing the challenges posed by tumor heterogeneity in breast cancer.

Reactive oxygen species produced by photodynamic therapy enhance docosahexaenoic acid lipid peroxidation and induce the death of breast cancer cells.

Breast cancer remains a serious threat to women's physical and emotional health. The combination therapies can overcome the deficiency of single therapy, enhance the therapeutic effects and reduce the side effects at the same time. In this study, we synthesize a novel nanomedicine that enhanced the therapeutic effects of breast cancer treatment by combining photodynamic therapy and chemotherapy. The doxorubicin (DOX) and photosensitizer methyl pyropheophorbide-a (MPPa) are loaded into the nano-drug delivery system as DPSPFA/MPPa/DOX. In response to near-infrared (NIR) laser, the drugs were quickly released to the cancer cells. The MPPa produces reactive oxygen species (ROS) under the action of photodynamics. Unsaturated fatty acids with ROS promotes lipid peroxidation and the combination of chemotherapy and photodynamic therapy. The data shows that the DPSPFA/MPPa/DOX has a spherical shape, good dispersibility and stability, and the particle size is roughly 200 nm. The drug loading capability of DOX is about 13 %. Both of MCF7 cell model in vitro and breast cancer model in vivo, DPSPFA/MPPa/DOX showed an excellent anti-tumor effect of 86.9 % and without any obvious side effects. These findings might offer potential for a new approach for breast cancer treatment.

Hippocampal-derived extracellular vesicle synergistically deliver active adenosine hippocampus targeting to promote cognitive recovery after stroke.

Ischemic stroke is a neurological disease that leads to brain damage and severe cognitive impairment. In this study, extracellular vesicles(Ev) derived from mouse hippocampal cells (HT22) were used as carriers, and adenosine (Ad) was encapsulated to construct Ev-Ad to target the damaged hippocampus. The results showed that, Ev-Ad had significant antioxidant effect and inhibited apoptosis. In vivo, Ev-Ad reduced cell death and reversed inflammation in hippocampus of ischemic mice, and improved long-term memory and learning impairment by regulating the expression of the A1 receptor and the A2A receptor in the CA1 region. Thus, the developmental approach based on natural carriers that encapsulating Ad not only successfully restored nerves after ischemic stroke, but also improved cognitive impairment in the later stage of ischemic stroke convalescence. The development and design of therapeutic drugs provides a new concept and method for the treatment of cognitive impairment in the convalescent phase after ischemic stroke.

Preparation of injectable porcine skin-derived collagen and its application in delaying skin aging by promoting the adhesion and chemotaxis of skin fibroblasts.

Collagen, as the main component of human skin, plays a vital role in maintaining dermal integrity. Its loss will lead to dermis destruction and collapse, resulting in skin aging. At present, injection of exogenous collagen is an important means to delay skin aging. In this study, high-purity collagen was extracted from porcine skin. Our research revealed that it can effectively promote the adhesion and chemotaxis of HSF cells. It can also reduce the expression of ß-galactosidase, decrease ROS levels, and increase the expression of the collagen precursors, p53 and p16 in HSF cells during senescence. After local injection into the aging skin of rats, it was found that the number of cells and type I collagen fibers in the dermis increased significantly, and the arrangement of these fibers became more uniform and orderly. Moreover, the important thing is that it is biocompatible. To sum up, the porcine skin collagen we extracted is an anti-aging biomaterial with application potential.

Tumor cell-derived extracellular vesicles for breast cancer specific delivery of therapeutic P53.

Breast cancer has consistently had the highest incidence among women in the world. Tumor cell-derived extracellular vesicles (EV) have been leveraged as drug carriers for cancer treatment. Herein, we developed an efficient theranostic platform for breast cancer-specific delivery of lipophilic triphenylphosphonium (TPP)-modified therapeutic recombinant P53 proteins (TPP/P53) by breast cancer cell-derived EVs. We observed that the EVs were routinely captured by their patent cells, so when, TPP/P53 was loaded into the EVs (TPP/P53@EVs), TPP/P53 was targeted to the mitochondria of breast cancer cells, where it caused signal amplification and induced the death of breast cancer cells. Our findings demonstrated that the TPP/P53@EVs showed good tumor-targeting capability and efficiently destroyed the tumor tissues without any obvious toxicity in vivo. Therefore, our TPP/P53@EVs might provide a "drug-free" strategy for future applications in breast cancer therapy.

Multi-ligand modified PC@DOX-PA/EGCG micelles effectively inhibit the growth of ER+, PR+ or HER2+ breast cancer.

Breast cancer is one of the most common cancers in the world with tumor heterogeneity. Currently, cancer treatment mainly relies on surgical intervention, chemotherapy, and radiotherapy, for which the side effects, drug resistance and cost need to be resolved. In this study, we develop a natural medicine targeted therapy system. Phosphatidylcholine (PC), doxorubicin (DOX), procyanidin (PA), and epigallocatechin gallate (EGCG) are assembled and PC@DOX-PA/EGCG nanoparticles (NPs) are obtained. In addition, the HER2, ER and PR ligands were grafted on the surface of the NPs to acquire the targeted nanoparticles NP-ER, NP-ER-HER2, and NP-ER-HER2-PR. The physicochemical properties of the nanoparticles were detected and it was found that the nanoparticles are spherical and less than 200 nm in diameter. Furthermore, in vitro and in vivo results indicate that the nanoparticles can target BT-474, MCF-7, EMT-6, and MDA-MB-231 breast cancer cells, effectively inhibiting the growth of the breast cancer cells. In short, this research will provide some strategies for the treatment of heterogeneous breast cancer.

NIR-Assisted MgO-Based Polydopamine Nanoparticles for Targeted Treatment of Parkinson's Disease through the Blood-Brain Barrier.

The blood-brain barrier (BBB) is a major limiting factor that prevents the treatment of Parkinson's disease (PD). In the present study, MgOp@PPLP nanoparticles are explored by using MgO nanoparticles as a substrate, polydopamine as a shell, wrapping anti-SNCA plasmid inside, and modifying polyethylene glycol, lactoferrin, and puerarin on the surface to improve the hydrophilicity, brain targeting and antioxidant properties of the particles, respectively. MgOp@PPLP exhibits superior near-infrared radiation (NIR) response. Under the guidance of photothermal effect, these MgOp@PPLP particles are capable of penetrating the BBB and be taken up by neuronal cells to exert gene therapy and antioxidant therapy. In both in vivo and in vitro models of PD, MgOp@PPLP exhibits good neuroprotective effects. Therefore, combined with noninvasive NIR radiation, MgOp@PPLP nanoplatform with good biocompatibility becomes an ideal material to combat neurodegenerative diseases.

Raloxifene Prevents Early Periprosthetic Bone Loss for Postmenopausal Women after Uncemented Total Hip Arthroplasty: A Randomized Placebo-Controlled Clinical Trial.

OBJECTIVE: To examine the results of raloxifene for prevention of periprosthetic bone loss around the femoral stem in patients undergoing total hip arthroplasty (THA). METHODS: Between January 2015 and May 2017, 240 female patients between 55 and 80 years underwent primary THA and were randomly allocated to receive 60 mg raloxifene hydrochloride per day (treatment group, TG, n = 120) or placebo (control group, CG, n = 120) orally at bedtime using computer-generated randomization sequence generation. Baseline data, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), women's quality of life (QoL) score, bone mineral density (BMD) around the prosthesis, and adverse events were compared between the two groups. The measuring range of BMD around the prosthesis was divided into seven regions of interest (ROI). The sample size was calculated to detect a mean difference in BMD of 0.15 g/cm2 with a standard deviation (SD) of 0.3. The error was set at 0.05 and the power level at 90% with additional compensation for a possible dropout rate of 20%. RESULTS: A total of 240 participants in the study up to 24 months after THA. There were no significant differences in the mean BMD of all the zones between groups before surgery (all P > 0.05). However, there were significant differences in the BMD of Gruen zones 4 and 7 between groups at 6 months postoperatively (both P < 0.05); there were significant differences in Gruen zones 1, 4, 6, and 7 at 12 months postoperatively (all P < 0.01); there were significant differences in Gruen zones 1, 2, 4, 6, and 7 at 24 months postoperatively (all P < 0.001). Patients taking raloxifene reported higher QoL scores, with better improvement in BMD in all areas except in zones 3 and 5 compared with the control group. There were no significant differences in WOMAC pain (P = 0.4045), WOMAC function (P = 0.4456) and women's QoL scores (P = 0.5983) between groups before surgery. However, WOMAC pain, WOMAC function and women's QoL score in the treatment group were significantly better at all time points (all P < 0.05). Patients in the treatment group showed no increased adverse events, including cardiac events, stroke, venous thromboembolism, and gynecological cancer (all P > 0.05), but did show decreased odds of breast cancer in comparison with those using a placebo (P = 0.0437). CONCLUSION: Raloxifene can help inhibit bone loss around the prosthesis and improve the QoL of postmenopausal women after THA with no increased adverse events, and can even decrease the odds of breast cancer.

Growth factors regional patterned and photoimmobilized scaffold applied to bone tissue regeneration.

Bone diseases such as osteomalacia, osteoporosis, and osteomyelitis are major illnesses that threaten the health of human. This study aimed to provide an idea at the molecular level of material properties determined with UV specific surface approaches. The tert-butyl hydroperoxide (t-BHP) exposure aging model bone mesenchymal stem cells (BMSCs) were reverted by using a poly-hybrid scaffold (PS), which is a carbon nanotube (CNT) coated polycaprolactone (PCL) and polylactic acid (PLA) scaffold, combined with insulin-like growth factor-1 (IGF). Then, the region-specific PS photo-immobilized with different growth factors (GFs) was obtained by interference and diffraction of ultraviolet (UV) light. Additionally, the reverted BMSCs were regionally pattern differentiated into three kinds of cells on the GF immobilized PS (GFs/PS). In vivo, the GFs/PS accelerate bone healing in injured Sprague-Dawley (SD) rats. The data showed that GFs/PS effectively promoted the differentiation of reverted BMSCs in the designated area on 21st day. These results suggest region-specific interface immobilization of GFs concurrently differentiating reverted BMSCs into three different cells in the same scaffold. This method might be considered as a short-time, low cost, and simple operational approach to scaffold modification for tissue regeneration in the future.

Inhibition by Multifunctional Magnetic Nanoparticles Loaded with Alpha-Synuclein RNAi Plasmid in a Parkinson's Disease Model.

Lewy bodies are considered as the main pathological characteristics of Parkinson's disease (PD). The major component of Lewy bodies is α-synuclein (α-syn). The use of gene therapy that targeting and effectively interfere with the expression of α-syn in neurons has received tremendous attention. In this study, we used magnetic Fe3O4 nanoparticles coated with oleic acid molecules as a nano-carrier. N-isopropylacrylamide derivative (NIPAm-AA) was photo-immobilized onto the oleic acid molecules, and shRNA (short hairpin RNA) was absorbed. The same method was used to absorb nerve growth factor (NGF) to NIPAm-AA to specifically promote neuronal uptake via NGF receptor-mediated endocytosis. Additionally, shRNA plasmid could be released into neurons because of the temperature and pH sensitivity of NIPAm-AA interference with α-syn synthesis. We investigated apoptosis in neurons with abrogated α-syn expression in vitro and in vivo. The results demonstrated that multifunctional superparamagnetic nanoparticles carrying shRNA for α-syn could provide effective repair in a PD model.