Jiaojiao Liu

Tunable dual-stimuli response of a microgel composite consisting of reduced graphene oxide nanoparticles and poly(N-isopropylacrylamide) hydrogel microspheres

A type of photo- and thermo-responsive composite microsphere composed of reduced graphene oxide nanoparticles and poly(N-isopropylacrylamide) (rGO@pNIPAM) is successfully fabricated by a facile solution mixing method. Due to the high optical absorbance and thermal conduction of rGO, the composite microspheres are endowed with the new property of photo-response, in addition to the intrinsic thermally sensitive property of pNIPAM. This new ability undoubtedly enlarges the scope of applications of the microgel spheres. Furthermore, through controlling the rGO content in the composite, the photo- and thermo-sensitivity of the composite can be effectively modulated. That is, with a lower rGO content (≤32% by weight), the composite microspheres perform only thermally induced changes, such as volume contraction (by ∼45% in diameter) and drug release, when crossing the lower critical solution temperature of pNIPAM. With a higher rGO content (∼47.5%), both temperature and light irradiation can trigger changes in the composite. However, when the rGO content is increased to around 64.5%, the thermo-responsivity of the composite disappears, and the spheres exhibit only photo-induced drug release. With a further increase in rGO content, the environmentally responsive ability of the microspheres vanishes.

Influence of surface chemistry on particle internalization into giant unilamellar vesicles

Cellular uptake of materials plays a key role in their biomedical applications. In this work, based on the cell-mimic giant unilamellar vesicles (GUVs) and a novel type of microscale materials consisting of stimuli-responsive poly(N-isopropylacrylamide) microgel particles and the incorporated lipids, the influence of particle surface chemistry, including hydrophobic/hydrophilic property and lipid decorations, on the adsorption and consequent internalization of particles into GUVs was investigated. It is found that the decoration of particle surface with lipids facilitates the adsorption of particles on GUV membrane. After that, the hydrophobic property of particle surface further triggers the internalization of particles into GUVs. These results demonstrate the importance of surface properties of particles on their interactions with lipid membranes and are helpful to the understanding of cellular uptake mechanism.

Reduced graphene oxide directed self-assembly of phospholipid monolayers in liquid and gel phases.

The response of cell membranes to the local physical environment significantly determines many biological processes and the practical applications of biomaterials. A better understanding of the dynamic assembly and environmental response of lipid membranes can help understand these processes and design novel nanomaterials for biomedical applications. The present work demonstrates the directed assembly of lipid monolayers, in both liquid and gel phases, on the surface of a monolayered reduced graphene oxide (rGO). The results from atomic force microscopy indicate that the hydrophobic aromatic plane and the defect holes due to reduction of GO sheets, along with the phase state and planar surface pressure of lipids, corporately determine the morphology and lateral structure of the assembled lipid monolayers. The DOPC molecules, in liquid phase, probably spread over the rGO surface with their tails associating closely with the hydrophobic aromatic plane, and accumulate to form circles of high area surrounding the defect holes on rGO sheets. However, the DPPC molecules, in gel phase, prefer to form a layer of continuous membrane covering the whole rGO sheet including defect holes. The strong association between rGO sheets and lipid tails further influences the melting behavior of lipids. This work reveals a dramatic effect of the local structure and surface property of rGO sheets on the substrate-directed assembly and subsequent phase behavior of the supported lipid membranes.

Encapsulation of Hydrophobic Phthalocyanine with Poly(N-isopropylacrylamide)/Lipid Composite Microspheres for Thermo-Responsive Release and Photodynamic Therapy

Phthalocyanine (Pc) is a type of promising sensitizer molecules for photodynamic therapy (PDT), but its hydrophobicity substantially prevents its applications. In this study, we efficiently encapsulate Pc into poly(N-isopropylacrylamide) (pNIPAM) microgel particles, without or with lipid decoration (i.e., Pc@pNIPAM or Pc@pNIPAM/lipid), to improve its water solubility and prevent aggregation in aqueous medium. The incorporation of lipid molecules significantly enhances the Pc loading efficiency of pNIPAM. These Pc@pNIPAM and Pc@pNIPAM/lipid composite microspheres show thermo-triggered release of Pc and/or lipid due to the phase transition of pNIPAM. Furthermore, in the in vitro experiments, these composite particles work as drug carriers for the hydrophobic Pc to be internalized into HeLa cells. After internalization, the particles show efficient fluorescent imaging and PDT effect. Our work demonstrates promising candidates in promoting the use of hydrophobic drugs including photosensitizers in tumor therapies.

Silicon quantum dots delivered phthalocyanine for fluorescence guided photodynamic therapy of tumor

Imaging-guided cancer therapy provides a simultaneous tumor imaging and treatment, which helps to eliminate the excessive toxicity to the healthy tissues. For this purpose, multifunctional probes capable of both imaging and curing are needed. In this work, we synthesize water-soluble silicon quantum dots (Si QDs) smaller than 5 nm. Such Si QDs are used for delivering the hydrophobic drug phthalocyanine (Pc). The as-prepared Si/Pc nanocomposite particles show efficient transmembrane delivery into cells and feasible biocompatibility. Moreover, these composite particles emit dual-channel fluorescence signals even after cellular internalization and demonstrate robust photostability in the Si channel. More interestingly, the Si/Pc composite particles show efficient photodynamic therapy effects against tumors both in vitro and in vivo.

Manipulation of cellular orientation and migration by internalized magnetic particles

The quick response of magnetic nanoparticles (MNPs) to an external field provides a unique way for cellular manipulation in a remote and non-contact mode. In this work, we demonstrate the modulation of cellular behaviors including orientation and migration based on internalized Fe3O4 nanoparticles in a particle-concentration dependent manner. After being treated with MNPs at low concentrations (e.g. 0.277 μg mL−1), the internalized particles separately distributed around the nuclei, and somewhat influenced the orientation of the cells along the direction of the external magnetic field. In contrast, when the concentration of MNPs was high enough (e.g. 2.770 μg mL−1), the particles formed clusters within the cells and moved towards the edges of the cell in the direction of the magnetic field, leading to an obvious morphological change and subsequently a directed migration of the cells. This result shows a facile way to manipulate cell behaviors with excellent biocompatibility and its potential application in the biomedical field such as in tissue engineering.

Photoluminescence modulation of silicon nanoparticles via highly ordered arrangement with phospholipid membranes

Highly ordered self-assembly of nanoparticles (NPs) in a large scale promises attractive potential in optical modulation of the NPs for illuminating, imaging and sensing applications. In this work, a type of multi-lamellar nanocomposite membranes composed of phospholipid multilayers and Si NPs sandwiched between each adjacent lipid layers was fabricated via a facile co-assembly method. X-ray reflectivity (XRR), grazing incident X-ray diffraction (GIXRD) and TEM measurements verified the highly ordered arrangement of NPs within the multilayers with a controlled in-plane inter-particle separation from ∼7 nm to ∼14 nm. Due to such an arrangement, the photoluminescence (PL) properties of the Si NPs were effectively modulated. Compared to the NPs in suspension or its pure film, the PL of the NPs in the membranes blue-shifted and remarkably narrowed, with the full-width-at-half-maximum (FWHM) value reduced from >110 nm of the pure Si NP film to below 43 nm. The radiative lifetime of the NPs was also significantly reduced from ∼16.7 ns to ∼3.3 ns depending on the inter-particle distance in the membrane. Meanwhile, the Si NPs within membranes maintained robust photostability under UV irradiation.

Molecular details on the intermediate states of melittin action on a cell membrane

Antimicrobial peptides (AMPs) provide a promising solution to the serious threat of multidrug-resistant bacteria or superbugs to public healthcare, due to their unique disruption to bacterial membrane such as perforation. Unfortunately, the underlying action mechanism of AMPs, especially the possible transition between the membrane binding and perforation states of peptides (i.e., the classical two-state model), is still largely unknown. Herein, by combining experimental techniques with pertinent membrane models and molecular dynamic (MD) simulations, new insights into the intermediate states of the AMP melittin-membrane interaction process are obtained. Specifically, it is demonstrated that, after the initial binding, the accumulated melittin on the bilayer triggers vigorous fluctuation of the membrane and even extracts some lipid molecules exclusively from the deformed outer leaflet of the bilayer. Such a distinctive mass removal manner and the resultant local asymmetry in lipid number between the two leaflets change the mechanical status of the membrane and in turn reduce the free energy barrier for the melittin insertion. Finally, the formation of the transmembrane pores is facilitated significantly. These findings provide new insights into the complicated antimicrobial mechanisms of AMPs.

Self-assembly of monolayered lipid membranes for surface-coating of a nanoconfined Bombyx mori silk fibroin film

Regenerated Bombyx mori (B. mori) silk fibroin is a type of widely used biomaterial. The β-sheet structure of it after methanol treatment provides water-insolubility and mechanical stability while on the other side leads to a hydrophobic surface which is less preferred by biological systems. In this work we prepare a novel type of nanoconfined silk fibroin film with a thickness below 100 nm. The film has a flat while hydrophobic surface because of its β-sheet structure due to the z-direction confinement during formation. Different types of lipid monolayers, DOPC, DPPC and MO, are assembled on the silk film surface. The lipid coating, especially the DPPC membrane, provides a much smoother and more hydrophilic surface due to the gel phase tails of the lipids, in comparison with the DOPC and MO ones which are in a liquid phase and have a much stronger interfacial association between silk film surface and lipid tails. Such a lipid coating preserves the biocompatibility and cellular affinity of the silk film which promises potential applications as surface coatings for materials for biological use.