Guanghui Ma

Preparation of Hierarchical Hollow CaCO3 Particles and the Application as Anticancer Drug Carrier

One-pot approach to couple the crystallization of CaCO(3) nanoparticles and the in situ symmetry-breaking assembly of these crystallites into hollow spherical shells was developed under the templating effect of a soluble starch. Further functional study using HP-a as an anticancer drug carrier (DOX) demonstrated its advantages for localizing drug release by the pH value-sensitive structure and enhancing cytotoxicity by increasing cellular uptake, perinuclear accumulation, and nuclear entry.

Surface Charge Affects Cellular Uptake and Intracellular Trafficking of Chitosan-Based Nanoparticles

Chitosan-based nanoparticles (NPs) are widely used in drug delivery, device-based therapy, tissue engineering, and medical imaging. In this aspect, a clear understanding of how physicochemical properties of these NPs affect the cytological response is in high demand. The objective of this study is to evaluate the effect of surface charge on cellular uptake profiles (rate and amount) and intracellular trafficking. We fabricate three kinds of NPs (∼ 215 nm) with different surface charge via SPG membrane emulsification technique and deposition method. They possess uniform size as well as identical other physicochemical properties, minimizing any differences between the NPs except for surface charge. Moreover, we extend our research to eight cell lines, which could help to obtain a representative conclusion. Results show that the cellular uptake rate and amount are both positively correlated with the surface charge in all cell line. Subsequent intracellular trafficking indicates that some of positively charged NPs could escape from lysosome after being internalized and exhibit perinuclear localization, whereas the negatively and neutrally charged NPs prefer to colocalize with lysosome. These results are critical in building the knowledge base required to design chitosan-based NPs to be used efficiently and specifically.

Simple Peptide-Tuned Self-Assembly of Photosensitizers towards Anticancer Photodynamic Therapy

Peptide-tuned self-assembly of functional components offers a strategy towards improved properties and unique functions of materials, but the requirement of many different functions and a lack of understanding of complex structures present a high barrier for applications. Herein, we report a photosensitive drug delivery system for photodynamic therapy (PDT) by a simple dipeptide- or amphiphilic amino-acid-tuned self-assembly of photosensitizers (PSs). The assembled nanodrugs exhibit multiple favorable therapeutic features, including tunable size, high loading efficiency, and on-demand drug release responding to pH, surfactant, and enzyme stimuli, as well as preferable cellular uptake and biodistribution. These features result in greatly enhanced PDT efficacy in vitro and in vivo, leading to almost complete tumor eradication in mice receiving a single drug dose and a single exposure to light.

An Injectable Self‐Assembling Collagen–Gold Hybrid Hydrogel for Combinatorial Antitumor Photothermal/Photodynamic Therapy

An injectable and self-healing collagen-gold hybrid hydrogel is spontaneously formed by electrostatic self-assembly and subsequent biomineralization. It is demonstrated that such collagen-based hydrogels may be used as an injectable material for local delivery of therapeutic agents, showing enhanced antitumor efficacy.

The role of the lateral dimension of graphene oxide in the regulation of cellular responses

The nanomaterial graphene oxide (GO) has attracted explosive interests in various areas. However, its performance in biological environments is still largely unknown, particularly with regard to cellular response to GO. Here we separated the GO sheets in different size and systematically investigated size effect of the GO in response to different types of cells. In terms of abilities to internalize GO, enormous discrepancies were observed in the six cell types, with only two phagocytes were found to be capable of internalizing GO. The 2 μm and 350 nm GO greatly differed in lateral dimensions, but equally contributed to the uptake amount in macrophages. Similar amounts of antibody opsonization and active Fcγ receptor-mediated phagocytosis were demonstrated the cause of this behavior. In comparison with the nanosized GO, the GO in micro-size showed divergent intracellular locations and induced much stronger inflammation responses. Present study provided insight into selective internalization, size-independent uptake, and several other biological behaviors undergone by GO. These findings might help build necessary knowledge for potential incorporation of the unique two-dimensional nanomaterial as a biomedical tool, and for avoiding potential hazards.

Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin

The alginate-chitosan microspheres with narrow size distribution were prepared by membrane emulsification technique in combination with ion (Ca(2+)) and polymer (chitosan) solidification. The preparation procedure was observed, and the physical properties (particle size distribution, surface morphology, chitosan distribution, zeta potential) of the microspheres were characterized. Subsequently, the microspheres were employed to load model peptide of insulin. The effect of loading ways on the loading efficiency and immunological activity of insulin were investigated. It was shown that the higher loading efficiency (56.7%) and remarkable activity maintenance (99.4%) were obtained when the insulin was loaded during the chitosan solidification process (Method B). Afterward, the release profile in vitro for the optimal insulin-loaded microspheres was investigated. Under the pH conditions of gastrointestinal environment, only 32% of insulin released during the simulated transit time of drug (2 h in the stomach and 4 h in the intestinal). While under the pH condition of blood environment, insulin release was stable and sustained for a long time (14 days). Furthermore, the chemical stability of insulin released from the microspheres was well preserved after they were treated with the simulated gastric fluid containing pepsin for 2 h. Finally, the blood glucose level of diabetic rats could be effectively reduced and stably kept for a long time (∼60 h) after oral administration of the insulin-loaded alginate-chitosan microspheres. Therefore, the alginate-chitosan microspheres were found to be promising vectors showing a good efficiency in oral administration of protein or peptide drugs.

One Dimensional CuInS2-ZnS Heterostructured Nanomaterials as Low-Cost and High-Performance Counter Electrodes of Dye-Sensitized Solar Cells

Wurtzite CuInS2-ZnS heterostructured nanorods are synthesized via a seed-assisted synthetic route. Cu1.94S-ZnS heterostructured nanorods are transformed into CuInS2-ZnS by reacting with indium ions to convert copper sulfide to wurtzite CuInS2. The shapes of the CuInS2-ZnS heterostructured nanorods can be tuned from burning torch-like to longer rod-like by varying the concentration of added indium. Dye-sensitized solar cells (DSSCs) using these heterostructured nanocrystals as counter electrodes had a power conversion efficiency (7.5%) superior to DSSCs made with conventional platinum electrode (7.1%) under the same device configuration.

W/O/W double emulsion technique using ethyl acetate as organic solvent: effects of its diffusion rate on the characteristics of microparticles.

Monomethoxypoly(ethylene glycol)-b-poly(DL-lactide) copolymer (PELA) microparticles loading lysozyme were prepared through a modified W/O/W double emulsion-solvent diffusion method using ethyl acetate (EA) as organic solvent. The modified process was divided into five steps: (1) primary emulsification (W1/O), (2) re-emulsification (W1/O/W2), (3) pre-solidification, (4) solidification and (5) purification. The pre-solidification step was carried out in the modified process to control the diffusion rate of EA from oil phase into outer aqueous phase, in order to prevent the wall polymer from precipitation, which usually occurred when the diffusion rate was too fast. The adequately rapid solidification of microparticle caused by controlled fast diffusion of EA and the use of amphiphilic copolymer PELA as wall material, facilitated a high protein entrapment (always above 94%) and full preservation of bioactivity of entrapped lysozyme. It was found that the volume of the outer aqueous phase in the re-emulsification step and the shear stress in the pre-solidification step had a significant effect on the diffusion rate of EA from the droplets into outer aqueous solution, and thereby on the characteristics of the resultant microparticles. With the volume or the shear stress increasing, the removal rate of EA increased, resulting in rapid solidification of the microparticles. This result led to a lower burst effect and a slower lysozyme release from the microparticles. This study suggests that the modified W/O/W double emulsion-solvent diffusion method with EA as organic solvent is a prospective technique to prepare biodegradable microparticles containing water-soluble sensitive agents.

Particle size affects the cellular response in macrophages

A deeper understanding of how the physical properties of particles regulate specific biological responses is becoming a crucial requirement for their successful biomedical application. To provide insights on their design and application, J774A.1 cells are exposed to particles with different diameters (430 nm, 1.9 μm and 4.8 μm), and the size effects on a series of cellular responses in macrophages are evaluated. Cellular uptake study demonstrates that nanosized particles accumulate in the cells at a faster rate, and with a higher surface area. Once the data are converted into the expression of particle volume, the maximum value is found with 1.9 μm particles instead of nanoparticles. Moreover, the uptake intermediates are also trapped, and the steps of particle internalization include filopodia sensing, skeleton rearrangement, and morphology change. Subsequent cellular trafficking reveals that only nanosized particles transport via lysosomal pathway, which is consistent with their uptake mechanisms. Furthermore, nanosized particles prefer to promote the secretion of Th1-specific molecule signals (e.g. IFN, IL-12) rather than immune suppressors. All these results, along with a couple of surprises, are discussed in the view of clinical practice. They are expected, in principle, to establish the basis of new design concepts for particle-based biomedical applications.

Carrier-Free, Chemophotodynamic Dual Nanodrugs via Self-Assembly for Synergistic Antitumor Therapy

There are tremendous challenges from both tumor and its therapeutic formulations affecting the effective treatment of tumor, including tumor recurrence, and complex multistep preparations of formulation. To address these issues, herein a simple and green approach based on the self-assembly of therapeutic agents including a photosensitizer (chlorine e6, Ce6) and a chemotherapeutic agent (doxorubicin, DOX) was developed to prepare carrier-free nanoparticles (NPs) with the ability to inhibit tumor recurrence. The designed NPs were formed by self-assembly of Ce6 and DOX associated with electrostatic, π-π stacking and hydrophobic interactions. They have a relatively uniform size of average 70 nm, surface charge of -20 mV and high drug encapsulation efficiency, which benefits the favorable accumulation of drugs at the tumor region through a potential enhanced permeability and retention (EPR) effect as compared to their counterpart of free Ce6 solution. In addition, they could eradiate tumors without recurrence in a synergistic way following one treatment cycle. Furthermore, the NPs are safe without any activation of inflammation or immune response in separated organs. Taken together, the rationale of these pure nanodrugs via the self-assembly approach might open an alternative avenue and give inspiration to fabricate new carrier-free nanodrugs for tumor theranostics, especially for two small molecular antitumor drugs with the aim of combinational antitumor therapy in a synergistic way.