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.

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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 FeO 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.

In order to obtain high-strength and high-ductility Al–Si–Cu–Mg alloys, the present research is focused on optimizing the composition of soluble phases, the structure and morphology of insoluble phases, and artificial ageing processes. The results show that the best matches, 0.4 wt% Mg and 1.2 wt% Cu in the Al–9Si alloy, avoided the toxic effect of the blocky Al2Cu on the mechanical properties of the alloy. The addition of 0.6 wt% Zn modified the morphology of eutectic Si from coarse particles to fine fibrous particles and the texture of Fe-rich phases from acicular β-Fe to blocky π-Fe in the Al–9Si–1.2Cu–0.4Mg-based alloy. With the optimization of the heat treatment parameters, the spherical eutectic Si and the fully fused β-Fe dramatically improved the ultimate tensile strength and elongation to fracture. Compared with the Al–9Si–1.2Cu–0.4Mg-based alloy, the 0.6 wt% Zn modified alloy not only increased the ultimate tensile strength and elongation to fracture of peak ageing but also reduced the time of peak ageing. The following improved combination of higher tensile strength and higher elongation was achieved for 0.6 wt% Zn modified alloy by double-stage ageing: 100 °C × 3 h + 180 °C × 7 h, with mechanical properties of ultimate tensile strength (UTS) of ~371 MPa, yield strength (YS) of ~291 MPa, and elongation to fracture (E%) of ~5.6%.

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The presence of blood-brain barrier (BBB) that limits effective penetration of therapeutics is the main reason for poor outcomes of glioblastoma (GBM) treatment. Ultrasound (US) combined with microbubbles (MBs) can precisely disrupt the tight junctions of brain endothelial cells, thus creating "acoustic pores" and non-invasive opening the BBB. Here, chitosan oligosaccharide (COS) is conjugated with a sonosensitizer protoporphyrin IX (PpIX) and an immune-enhancing adjuvant Poly(I:C) via electrostatic adsorption, and crosslinked with a tumor-targeting molecule hyaluronic acid (HA) affording nanosonosensitizers HA-Poly(I:C)/COS-PpIX (abbreviated as "HP/CP" NSs). HP/ CP NSs can target and penetrate GBMs, and trigger reactive oxygen species production upon US, simultaneously causing mitochondrial dysfunction and DNA damage. Tumor-associated antigens released by sonodynamic therapyinduced immunogenic cell death and loaded Poly(I:C) form an in situ vaccine together to potentiate antitumor immune responses. In orthotopic GBM mice models, the HP/CP+US treatments prolong mice survival, enhance cytotoxic T-lymphocytes infiltration, and activate peripheral immune circulation. Besides, HP/CP NSs possess favorable biosafety profiles. Collectively, this study sheds light on the application of HP/CP NSs for synergistic sonoimmunotherapy of GBMs after non-invasive opening of the BBB.

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