Jine Wang

Charge-Reversal APTES-Modified Mesoporous Silica Nanoparticles with High Drug Loading and Release Controllability

In this study, we demonstrate a facile strategy (DL-SF) for developing MSN-based nanosystems through drug loading (DL, using doxorubicin as a model drug) followed by surface functionalization (SF) of mesoporous silica nanoparticles (MSNs) via aqueous (3-aminopropyl)triethoxysilane (APTES) silylation. For comparison, a reverse functionalization process (i.e., SF-DL) was also studied. The pre-DL process allows for an efficient encapsulation (encapsulation efficiency of ∼75%) of an anticancer drug [doxorubicin (DOX)] inside MSNs, and post-SF allows in situ formation of an APTES outer layer to restrict DOX leakage under physiological conditions. This method makes it possible to tune the DOX release rate by increasing the APTES decoration density through variation of the APTES concentration. However, the SF-DL approach results in a rapid decrease in drug loading capacity with an increase in APTES concentration because of the formation of the APTES outer layer hampers the inner permeability of the DOX drug, resulting in a burst release similar to that of undecorated MSNs. The resulting DOX-loaded DL-SF MSNs present a slightly negatively charged surface under physiological conditions and become positively charged in and extracellular microenvironment of solid tumor due to the protonation effect under acidic conditions. These merits aid their maintenance of long-term stability in blood circulation, high cellular uptake by a kind of skin carcinoma cells, and an enhanced intracellular drug release behavior, showing their potential in the delivery of many drugs beyond anticancer chemotherapeutics.

Formation of graphene oxide-hybridized nanogels for combinative anticancer therapy

The low efficacy and high toxicity of chemotherapy have been driving increasing attention on development of combined anticancer therapy technique. In the current work, graphene oxide (GO)-hybridized nanogels (AGD) were developed for delivery of an anticancer drug (doxorubicin (DOX)), which simultaneously presented photothermal therapeutic effects against cancer cells. AGD nanogels were fabricated by in situ incorporating GO nanoplatelets into a biodegradable polymer (alginate) via a double emulsion approach using a disulfide molecule as crosslinker, followed by DOX encapsulation via electrostatic interactions. The nanogels released DOX drug in an accelerated way under both acidic and reducible conditions mimicking extracellular tumor microenvironments and intracellular compartments. The stimulative release controllability of the nanogels improved the DOX internalization and long-term drug accumulation inside A549 cells (an adenocarcinoma human alveolar basal epithelial cell line), which, together with their photothermal effect, resulted in a good anticancer cytotoxicity, indicating their promising potential for combinative anticancer therapy.

Drug-mediation formation of nanohybrids for sequential therapeutic delivery in cancer cells

In order to overcome the multidrug resistance (MDR) of tumor cells, it is very important to develop nanocarriers which can effectively load drugs while releasing them in a sequential way. Herein, nanohybrids with such properties have been fabricated by a first loading of one anticancer drug onto a silicate nanodisk (Laponite (LP), 25 nm in diameter and 0.92 nm in thickness) and a subsequent assembly with a pH sensitive poly(N-vinylpyrrolidone) (PVP) as a protective layer, followed by a loading of with another anticancer drug. The resulting nanohybrids (LDPM) present a high drug encapsulation efficiency and long-term colloidal stability. However, if the two drugs are loaded onto LP before PVP decoration, the formed particles tend to form microsized aggregates with poor colloidal stability. In vitro release study indicates that LDPM can deliver the anticancer drugs in a sequential way, which can be further accelerated under acidic microenvironments mimicking both solid tumor and endo-lysosomal compartments, exerting synergistic anticancer cytotoxicity. The drug-mediated formation of nanocarriers may enlighten a design of novel nanoplatform for co-delivery of therapeutic agents, beyond anticancer drugs, in a combinative way for drug delivery applications.

In Situ formation of pH-/thermo-sensitive nanohybrids via friendly-assembly of poly(N-vinylpyrrolidone) onto LAPONITE®

The development of delivery nanosystems with a high payload, desirable release controllability, and cell responsiveness is important for an efficient and safe cancer therapy. In this study, multifunctional nanohybrids are successfully constructed by self-assembling a pH sensitive poly(N-vinylpyrrolidone) (PVP) onto LAPONITE® with a nanodisk structure (25 nm in diameter and 0.92 nm in thickness) in the absence of any organic solvent. The nanohybrids can effectively encapsulate a cationic anticancer drug, doxorubicin (DOX) through its electrostatic interactions with negatively-charged LAPONITE®. The hydrophobic component (alkane polymeric chain) of PVP can bind to the surface of LAPONITE®, with its hydrophilic components (ketone and tertiary amine residues) as a protective stealth shell for stabilization of the whole system. The deprotonation/protonation switchability of PVP endows the nanohybrids with good pH- and thermo-dual sensitivity in delivery of DOX drug, as compared to that modified with the polyethylene glycol (PEG, a common hydrophilic polymer for improving the stability of nanoparticles). In vitro biological evaluation indicated that the DOX-loaded nanocarriers can be effectively taken up by KB cells (a human epithelial carcinoma cell line), and exhibit uncompromising anticancer cytotoxicity as compared to free DOX, indicating their potential therapeutic delivery application.

Development of bioabsorbable polylactide membrane with controllable hydrophilicity for adjustment of cell behaviours

Cell functions can be mediated through their interactions with the microenvironments, which highly depend on the surface state of the substrate. However, how to finely adjust the surface of biomaterials is still very challenging. In this study, poly(d,l-lactide) (PDLLA) with high molecular weight was synthesized via ring opening polymerization, which was hot-pressed into PDLLA membrane. In order to modify the hydrophobicity of the membrane (a limiting factor for its biomedical application), an amphiphilic monomethoxyl poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PDLLA) was selected to improve its surface hydrophilicity through a simple self-assembly approach. It was found that the contact angles of the modified membrane can be well controlled by variation of PEG-PDLLA concentrations. In vitro cell biological study indicates that optimized cell adhesion can be achieved on the modified membrane with a contact angle of around 50° via its self-assembly with an ethanol/water solution of PEG-PDLA (35 mg ml−1). The surface modification of the membrane also changed its biodegradation property in the process of its incubation period up to 240 days. The surface modification method may afford an effective way for adjustment of the surface (interface) of membrane (scaffolds) of different biomaterials, beyond polylactide.