The surface/interface state of nanomaterials plays a key role on their biomedical applications. Nanotechnology offers a versatile means to develop nanoparticles with well-defined architecture. In this study, mesoporous silica nanoparticles were firstly loaded with an anticancer drug (doxorubicin, DOX), which were then decorated with a cationic oligomer (low molecular weight polyethyleneimine, LPEI) to acquire an increased surface charge. The resulting particles were further self-assembled with negative-charged bovine serum albumin (BSA) as natural protein nanoblocks to offer surface charge tunability. The resulting mesoporous nanohybrids (MDPB) acquired charge-reversal ability, which presented negative charge under biological conditions (beneficial to biocompatibility), while displaying a positive-charged state under acidic conditions mimicking the tumor extracellular microenvironment (favoring cell uptake or tumor penetration). Furthermore, the nanohybrids not only allowed for an effective loading of DOX drug, but also accelerated its release under acidic tumor microenvironments in a sustainable way. In vitro biological study indicated that the DOX-free nanoparticles were biocompatible, while MDPB exerted good cytotoxicity against cancer cells, suggesting their promise for therapeutic delivery application.

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.

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.

•MTC was used to promote the formation of raspberry-like NPs.•BA was incorporated to increase the film formability and film flexibility.•The relative ratio of SiO2 and BA affected physical properties of latex films.Raspberry-like P(St-BA)/SiO2 nanoparticle latexes were prepared via miniemulsion polymerization of styrene (St) and butyl acrylate (BA) in the presence of 20 nm glycerol-modified SiO2 sol as a Pickering emulsifier and octaphenyl polyoxyethylene (CA-897) as a nonionic surfactant, using 2,2-azobis (isobutyronitrile) (AIBN) as an initiator. 2-(Methacryloyl) ethyltrimethylammonium chloride (MTC) was introduced to act as an auxiliary monomer to enhance the attraction of SiO2 sol onto latex nanoparticles (NPs) via increasing their electrostatic interaction with negative-charged SiO2 sol. The average particle sizes of the latex particles can be well controlled from 200 to 360 nm by variation of the SiO2 sol content as well as soft monomer BA component. The latex NPs displayed a good colloidal stability with excellent resistance to both strong acidic and basic environment. Furthermore, the nanosized latexes exhibited good film formability. The influence of reaction parameters, e.g., the initial silica amount and soft monomer BA content was systematically investigated on the film performances, such as hardness, abrasive resistance, water absorption, gloss. The results indicated that the increase of SiO2 sol content can contribute to the increase of the film hardness and water absorption ability, while increasing BA component is beneficial to the improvement of the film gloss.

•β-TCP/PGS scaffold with robust mechanical property was developed for bone repair.•β-TCP/PGS scaffold was prepared by infiltration and in-situ crosslinking method.•The optimized β-TCP/PGS exhibited enhanced compressive strength and toughness.•PGS polymer could direct the biomineralization and balance the pH change.•β-TCP/PGS scaffolds favored for cell penetration and proliferation.Despite good biocompatibility and osteoconductivity, porous β-TCP scaffolds still lack the structural stability and mechanical robustness, which greatly limit their application in the field of bone regeneration. The hybridization of β-TCP with conventional synthetic biodegradable PLA and PCL only produced a limited toughening effect due to the plasticity of the polymers in nature. In this study, a β-TCP/poly(glycerol sebacate) scaffold (β-TCP/PGS) with well interconnected porous structure and robust mechanical property was prepared. Porous β-TCP scaffold was first prepared with polyurethane sponge as template and then impregnated into PGS pre-polymer solution with moderate viscosity, followed by in situ heat crosslinking and freezing–drying process. The results indicated that the freezing–drying under vacuum process could further facilitate crosslinking of PGS and formation of Ca2 +–COO− ionic complexing and thus synergistically improved the mechanical strength of the β-TCP/PGS with in situ heat crosslinking. Particularly, the β-TCP/PGS with 15% PGS content after heat crosslinking at 130 °C and freezing–drying at − 50 °C under vacuum exhibited an elongation at break of 375 ± 25% and a compressive strength of 1.73 MPa, 3.7-fold and 200-fold enhancement compared to the β-TCP, respectively. After the abrupt drop of compressive load, the β-TCP/PGS scaffolds exhibited a full recovery of their original shape. More importantly, the PGS polymer in the β-TCP/PGS scaffolds could direct the biomineralization of Ca/P from particulate shape into a nanofiber-interweaved structure. Furthermore, the β-TCP/PGS scaffolds allowed for cell penetration and proliferation, indicating a good cytobiocompatibility. It is believed that β-TCP/PGS scaffolds have great potential application in rigid tissue regeneration.Robust β-TCP/PGS porous scaffolds are developed by incorporation of poly(glycerol sebacate) (PGS, a flexible biodegradable polymer) into β-TCP scaffold. By impregnation of β-TCP scaffolds with low viscous PGS pre-polymer solution and further in situ crosslinking, the obtained β-TCP/PGS exhibited 3.7 time improvement in elongation at break and 200 time increase in strength as compared to pure β-TCP scaffolds, overcoming the brittleness of pure β-TCP scaffolds. Meanwhile, the β-TCP/PGS showed good pH auto-regulation ability and cytocompatibility.

The development of pH-sensitive drug delivery nanosystems that present a low drug release at the physiological pH and are able to increase the extent of the release at a lower pH value (like those existent in the interstitial space of solid tumors (pH 6.5) and in the intracellular endolysosomal compartments (pH 5.0)) is very important for an efficient and safe cancer therapy. Laponite (LP) is a synthetic silicate nanoparticle with a nanodisk structure (25 nm in diameter and 0.92 nm in thickness) and negative-charged surface, which can be used for the encapsulation of doxorubicin (DOX, a cationic drug) through electrostatic interactions and exhibit good pH sensitivity in drug delivery. However, the colloidal instability of LP still limits its potential clinical applications. In this study, we demonstrate an elegant strategy to develop stable Laponite-based nanohybrids through the functionalization of its surface with an amphiphile PEG–PLA copolymer by a self-assembly process. The hydrophobic block of PEG–PLA acts as an anchor that binds to the surface of drug-loaded LP nanodisks, maintaining the core structure, whereas the hydrophilic PEG part serves as a protective stealth shell that improves the whole stability of the nanohybrids under physiological conditions. The resulting nanocarriers can effectively load the DOX drug (the encapsulation efficiency is 85%), and display a pH-enhanced drug release behavior in a sustained way. In vitro biological evaluation indicated that the DOX-loaded nanocarriers can be effectively internalized by CAL-72 cells (an osteosarcoma cell line), and exhibit a remarkable higher anticancer cytotoxicity than free DOX. The merits of Laponite/PEG–PLA nanohybrids, such as good cytocompatibility, excellent physiological stability, sustained pH-responsive release properties, and improved anticancer activity, make them a promising platform for the delivery of other therapeutic agents beyond DOX.Keywords: amphiphilic polymer; anticancer; doxorubicin; Laponite; pH sensitive

•MTC was used to promote the formation of raspberry-like NPs.•BA was incorporated to increase the film formability and film flexibility.•The relative ratio of SiO2 and BA affected physical properties of latex films.Raspberry-like P(St-BA)/SiO2 nanoparticle latexes were prepared via miniemulsion polymerization of styrene (St) and butyl acrylate (BA) in the presence of 20 nm glycerol-modified SiO2 sol as a Pickering emulsifier and octaphenyl polyoxyethylene (CA-897) as a nonionic surfactant, using 2,2-azobis (isobutyronitrile) (AIBN) as an initiator. 2-(Methacryloyl) ethyltrimethylammonium chloride (MTC) was introduced to act as an auxiliary monomer to enhance the attraction of SiO2 sol onto latex nanoparticles (NPs) via increasing their electrostatic interaction with negative-charged SiO2 sol. The average particle sizes of the latex particles can be well controlled from 200 to 360 nm by variation of the SiO2 sol content as well as soft monomer BA component. The latex NPs displayed a good colloidal stability with excellent resistance to both strong acidic and basic environment. Furthermore, the nanosized latexes exhibited good film formability. The influence of reaction parameters, e.g., the initial silica amount and soft monomer BA content was systematically investigated on the film performances, such as hardness, abrasive resistance, water absorption, gloss. The results indicated that the increase of SiO2 sol content can contribute to the increase of the film hardness and water absorption ability, while increasing BA component is beneficial to the improvement of the film gloss.

•Decorating MSN with cationic oligmer (LPEI) affords charge-reversal ability.•LPEI shell is crosslinked to form nanogate with redox-degradability.•The obtained nanohybrids display a pH/redox-sensitive anticancer drug delivery.Although layer-by-layer assembly using anionic and cationic polymer has been a popular way to develop core-shell nanoparticles, the strong electrostatic interactions may limit shell degradability, thus hampering their application as a platform for controlled therapeutic delivery. In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-drug loading (using doxorubicin (DOX) as a model drug) into mesoporous silica nanoparticles (MSN), followed by surface functionalization with a kind of cationic oligomer (low molecular weight polyethylene imine, LPEI) and in situ crosslinking by degradable N,N′-bis(acryloyl)cystamine (BAC). The presence of LPEI shell affords the nanohybrids with charge-reversal ability, which means that the acidic tumor extracellular microenvironment can transform the negative surface charge at neutral conditions into positive-charged ones. The nanohybrids displayed a pH- and redox-dual sensitivity in DOX release under conditions that mimic intracellular reductive conditions and acidic tumor microenvironments. The nanohybrids can be effectively internalized into A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their high potential as a new platform for therapeutic delivery.