A new phenylboronic acid based gelator was developed to prepare low-molecular-weight organogel (LMOG), which could interact with several solvents to assemble into a three-dimensional nanofiber network. 1H NMR spectroscopy study suggests that the driving force for the gelation includes hydrogen bonding and π–π stacking. Evaluated by UV-spectroscopy, the gel showed a prompt initial response to glucose at low concentration of 0.012 mmol/mL, which is a critical concentration of venous plasma glucose for diabetes. Significantly, this organogel exhibits excellent sensitivity to glucose among seven sugars tested (i.e., mannitol, galactose, lactose, maltose, sucrose, and fructose). The proposed formation of hydrogen-bonded complexes during the glucose sensing was supported by our energy calculation. Meanwhile, this organogel exhibits pH-response. Importantly, this LMOG could be conveniently recycled and thus be reused.

With the aim of obtaining effective cancer therapy with simultaneous cellular imaging, dynamic drug-release monitoring, and chemotherapeutic treatment, a polymeric micelle with aggregation-induced emission (AIE) imaging and a Forster resonance energy transfer (FRET) effect was fabricated as the drug carrier. An amphiphilic conjugate of 1H-pyrrole-1-propanoicacid (MAL)–poly(ethylene glycol) (PEG)–Tripp-bearing AIE molecules were synthesized and self-assembled into micelles to load the anticancer drug doxorubicin (DOX). Spherical DOX-loaded micelles with the mean size of 106 nm were obtained with good physiological stability (CMC, 12.5 μg/mL), high drug-loading capacity (10.4%), and encapsulation efficiency (86%). The cellular uptake behavior of DOX-loaded MAL–PEG–Tripp micelles was visible for high-quality intracellular imaging due to the AIE property. The delivery of DOX from the drug-loaded micelles was dynamic monitored by the FRET effect between the DOX and MAL–PEG–Tripp. Both in vitro (IC50, 2.36 μg/mL) and in vivo anticancer activity tests revealed that the DOX-loaded MAL–PEG–Tripp micelles exhibited promising therapeutic efficacy to cancer with low systematic toxicity. In summary, this micelle provided an effective way to fabricate novel nanoplatform for intracellular imaging, drug-delivery tracing, and chemotherapy.

A novel low-molecular-weight hydrogel (LMWG) was fabricated by oligopeptide and phenylboronic acid to obtain a smart molecular hydrogel with dual glucose and pH response for long-term drug delivery in this study. Dual glucose and pH responsiveness of the blank molecular hydrogel was first evaluated by on-line tracking the dynamics curves using UV spectroscopy. Model drugs of phenformin for antidiabetes and doxorubicin for anticancer were selected to evaluate the drug carry and glucose/pH responsive drug release of the molecular hydrogel. The results showed the drug-loaded LMWG had good sustaining and long-lasting drug delivery in physiological or pathological environment.Download high-res image (296KB)Download full-size image

•Poly(pseudo)rotaxane micelle for anticancer drug delivery was fabricated.•The effect of α-cyclodextrin numbers on the drug loading properties was investigated.•The in vitro anticancer activity of the drug loaded micelles was studied.Poly(pseudo)rotaxane (PPR) nanoparticles was facilely prepared using poly(ethylene glycol) (PEG) modified with protoporphyrin (PpIX) and α-cyclodextrin (α-CD) via host-guest interaction, the effect of α-CD number on the nanoparticle properties was investigated. The PEG with protoporphyrin (PEG-PpIX) end capping was synthesized via coupling reaction and the poly(pseudo)rotaxane nanoparticles with different amount of α-CD were fabricated by host-guest interaction between mPEG-PpIX and α-CDs. The final product was characterized by nuclear magnetic spectrum (1H NMR), X-ray diffraction (XRD), atomic force microscope (AFM) and dynamic light scattering (DLS). The results showed that the poly(pseudo)rotaxane nanoparticles with uniform spherical shape was successfully prepared and doxorubicin (DOX) could be efficiently encapsulated in the nanoparticles. The amount of α-CDs in poly(pseudo)rotaxane nanoparticles was proportional to micellar size and drug release rate. The nanoparticles with higher α-CD number showed better anticancer efficacy in half maximal inhibitory concentration (IC50) test. The cell internalization efficiency of DOX-loaded poly(pseudo)rotaxane nanoparticles could be further improved by lowering the α-CD number to receive smaller nanoparticle size.

Low molecular weight gels (LMWGs) have significant advantages in drug delivery such as high drug loading capacity, in situ delivery of drug to the lesion site, sustaining drug release with excellent bioavailability, and minimized side effects. Here, we synthesized a reactive oxygen species (ROS)-responsive gelator to prepare an injectable gel. An anticancer drug, doxorubicin hydrochloride (DOX), and a photosensitizer, Zn(II) phthalocyanine tetrasulfonic acid (ZnPCS4), were loaded into the gel for combined chemo-photodynamic therapy. The ROS-responsive gelator was characterized by proton nuclear magnetic resonance (1H NMR) and the morphology of gels was investigated by scanning electron microscopy (SEM). The rheological properties and destruction–recovery capability of both blank and drug-loaded gels were studied. The cytotoxicity of LMWGs against 3T3 fibroblasts and 4T1 breast cancer cells was tested. The in vitro drug release of both drugs was studied and the in vivo anticancer activities of DOX–ZnPCS4-coloaded LMWGs were investigated in tumor-bearing mice. The results revealed that the injectable ROS-responsive DOX–ZnPCS4-coloaded LMWGs exhibited excellent anti-tumor efficacy by a synergistic therapy.

Four low molecular weight gels (LMWGs) with different moduli were fabricated as scaffolds to investigate the differentiation of mesenchymal stem cells (MSCs). The MSCs differentiated to osteoblasts in rigid LMWGs and to chondrocytes in soft LMWGs. The critical modulus to induce the different differentiations was between 10 and 20 kPa.

•A dual pH and temperature responsive hydrogel was fabricated.•The swelling behavior of the hydrogel was investigated.•The release profiles of atorvastatin from the hydrogel were studied.•The solubility of atorvastatin was improved greatly in the hydrogel.2-Methylacrylic acid modified β-cyclodextrin was copolymerized with 2-methylacrylic acid and N,N′-methylene diacrylamide to fabricate dual pH and temperature responsive hydrogels for the controlled release of atorvastatin. The swelling behaviors, pH and temperature responsive atorvastatin release profiles of the hydrogels were investigated. The results indicated that the hydrogel prepared in DMSO exhibited the best swelling rate, which was 51 for 10 min and 252 for 16 h when immersed in medium of buffer solution with pH = 8.06. The media with low (pH ≤ 3.84) and high (pH ≥ 10.34) pH values would reduce the swelling rate of hydrogels. The swelling of the hydrogel was increased with increasing temperature from 30 °C to 45 °C. Atorvastatin was loaded in the hydrogel for drug release investigation. The cumulative release rate of atorvastatin was as high as 90.5% in pH = 8.06 buffer solution. The solubility of atorvastatin was improved from 0.13 to 1.2 mg/mL in the hydrogel.

A near infrared (NIR) light responsive chromophore 7-(diethylamino)-4-(hydroxymethyl)-2H-chromen-2-one (DEACM) was synthesized and incorporated to β-cyclodextrins with cRGD functionalized poly(ethylene glycol), the amphiphiles were coordinated with Au nanorods or nanoparticles to load anticancer drug doxorubicin (DOX) for fabricating hybrid nanoparticles. The π-π stacking interaction between DEACM and DOX was formed in the hybrid nanoparticles, which contributed to the high drug loading content. The Au nanorods or nanoparticles enhanced the photosolvolysis of DEACM under the irradiation of NIR with 808 nm wavelength and triggered the accelerated drug release from the nanoparticles. The drug loaded hybrid nanoparticles with NIR irradiation exhibited efficient inhibition effect on the proliferation of 4T1 breast cancer cells in vitro. The in vivo anticancer activity study on breast cancer bearing mice revealed that the hybrid nanoparticles containing Au nanorods exhibited excellent anticancer activity under the irradiation of 808 nm wavelength NIR with 800 mW.

A series of phenylboronic acid (PBA)-based low-molecular-weight gelators with different hydrocarbon chain lengths (C2–C11) were designed and synthesized. These gelators gelated five solvents efficiently at relatively low concentration with interesting aggregates of nanofibers, thin films, spherical thin shells, and microspheres piled with nanofibers. The gelation ability increased with the chain length increasing up to C11, which has the lowest critical gelation concentration (CGC) of 0.19 wt %. FTIR and 1H NMR measurements suggested that van der Waals of alkyl chains, H-bonding, and π–π stacking interactions had an important contribution in gelation process and self-assembly. For all the gelators, their glucose-response increased along with the increasing concentration of glucose solution. However, the recognition and responsive rate to glucose were weakened gradually with the alkyl chain length increasing for the gelators. Therefore, glucose-sensitivity of these PBA-based organogels could be modulated through alkyl chain length.

•A novel dextran–rosuvastatin conjugate (DRC) was synthesized.•Multiple microparticles of DRC could be controlled self-assembled.•DRC microparticles had the characteristics of sustained-release in vitro.•The release manner could be adjusted by the morphology of DRC microparticles.A novel conjugate for rosuvastatin has been prepared by a coupling reaction between rosuvastatin and dextran. The dextran–rosuvastatin conjugates (DRC) were characterized by FT-IR, NMR, and XRD. And the resulting DRC self-assembled into microparticles by controlled slow exchange of solvents applying dialysis. The size and morphology of DRC microparticles could be controlled through the solvents and pH selection. Particles with different shape and size of microspheres, micro-blocks, micro-flakes or three-dimensional network structure were obtained by adjusting the pH from 9.0 to 13.0. Multiple morphologies of nano- or microparticles were collected in different organic solvents. In vitro release studies suggested that these DRC microparticles had a sustained release manner and the release behavior could be controlled by adjusting their morphology.

A new phenylboronic acid based gelator was developed to prepare low-molecular-weight organogel (LMOG), which could interact with several solvents to assemble into a three-dimensional nanofiber network. 1H NMR spectroscopy study suggests that the driving force for the gelation includes hydrogen bonding and π–π stacking. Evaluated by UV-spectroscopy, the gel showed a prompt initial response to glucose at low concentration of 0.012 mmol/mL, which is a critical concentration of venous plasma glucose for diabetes. Significantly, this organogel exhibits excellent sensitivity to glucose among seven sugars tested (i.e., mannitol, galactose, lactose, maltose, sucrose, and fructose). The proposed formation of hydrogen-bonded complexes during the glucose sensing was supported by our energy calculation. Meanwhile, this organogel exhibits pH-response. Importantly, this LMOG could be conveniently recycled and thus be reused.

Dextran propionate tryptophanate ester (DPT) was synthesized by two-step esterification to self-assemble into regular hollow nanospheres during a dialysis process. Hollow nanospheres self-assembled in the dimethylacetamide (DMAc) exchange against polymer solution, with a size in the range of 80–500 nm outside diameter and 15–110 nm shell thickness. The organic solvent had a great influence on the morphology and the size of these nanospheres. No hollow nanospheres but only nanoparticles with no cavum could self-assemble in furfuryl alcohol with the range of 57–257 nm, in DMSO with the range of 61–292 nm, in N-methyl-2-pyrrolidone with the range of 82–348 nm and in DMF with the range of 262–670 nm. The stability of these hollow nanospheres was also influenced by storage time. They were relatively stable in 2 months in deionized water stored at 25 °C or 37 °C, which can be verified by SEM and pH value variation.

Four low molecular weight gels (LMWGs) with different moduli were fabricated as scaffolds to investigate the differentiation of mesenchymal stem cells (MSCs). The MSCs differentiated to osteoblasts in rigid LMWGs and to chondrocytes in soft LMWGs. The critical modulus to induce the different differentiations was between 10 and 20 kPa.