Preparation and characterization of β-cyclodextrin grafted N-maleoyl chitosan nanoparticles for drug delivery

β-cyclodextrin (CD) grafted N-maleoyl chitosan (CD-g-NMCS) with two different degrees of substitution (DS) of N-maleoyl (DS = 21.2% and 30.5%) were synthesized from maleic anhydride and chitosan bearing pendant cyclodextrin (CD-g-CS). CD-g-NMCS based nanoparticles were prepared via an ionic gelation method together with chitosan and CD-g-CS nanoparticles.The size and zeta potential of prepared CD-g-NMCS nanoparticles were 179.2~274.0 nm and 36.2~42.4 m V, respectively. In vitro stability test indicated that CD-g-NMCS nanoparticles were more stable in phosphate-buffered saline compared with chitosan nanoparticles. Moreover, a poorly water-soluble drug, ketoprofen (KTP), was selected as a model drug to study the obtained nanoparticle’s potentials as drug delivery carriers. The drug loading efficiency of CD-g-NMCS20 nanoparticles were 14.8% for KTP. MTT assay showed that KTP loaded CD-g-NMCS nanoparticles were safe drug carriers. Notably, in vitro drug release studies showed that KTP was released in a sustained-release manner for the nanoparticles. The pharmacokinetic of drug loaded CD-g-NMCS20 nanoparticles were evaluated in rats after intravenous administration. The results of studies revealed that, compared with free KTP, KTP loaded CD-g-NMCS20 nanoparticles exhibited a significant increase in AUC0→24h and mean residence time by 6.6-fold and 2.9-fold, respectively. Therefore, CD-g-NMCS nanoparticles could be used as a novel promising nanoparticle-based drug delivery system for sustained release of poorly water-soluble drugs. The carboxylic acid groups of the CD-g-NMCS molecule provide convenient sites for further structural modifications including introduction of tissue-or disease-specific targeting groups.

Regulating photothermal properties of near-infrared croconaine dyes by supramolecular assembly

The photochemical and photophysical properties of near-infrared(NIR)dyes are significantly influenced by their aggregation state and mesoscopic morphology.However,beyond chemical synthesis,the regulation mechanisms for the properties of NIR dyes,particularly with respect to photothermal properties of the aggregates,are not yet fully understood.Here,we investigate the photothermal behaviors of croconaine-based(CroA)NIR dyes containing dipeptide or amino acids moieties.The introduction of hydrogen bonding promotesπ-πstacking of croconaine center,which can efficiently regulate aggregation states and assembly structures in isopropanol.Under laser irradiation,CroA aggregates undergo aggregation-dissociation transition,the in-situ monomer generation process regulates two parameters of photothermal performance:heating rates and plateau photothermal temperatures.This study reveals the regulation effect of non-covalent bonding interactions on CroA aggregates,highlighting supramolecular assembly strategy not only facilitates to construct of photothermal nanomaterials with well-defined structures,but also provides an alternative and effective method for regulating photothermal performance of NIR dyes.

A combination of Light On gene expression system and tumor microenvironment-responsive nanoparticle delivery system for targeted breast cancer therapy

A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light,and have great potential for spatiotemporally controllable gene expression.We developed a nanoparticle drug delivery system(NDDS)to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A(DTA)fragment-encoded plasmids to tumor sites.The expression of DTA was induced by exposure to blue light.Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond,and PEGylated hyaluronic acid modified with RGD peptide,accumulated in tumor tissues and were actively internalized into 4 T1 cells via dual targeting to CD44 andαvβ3 receptors.The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure.In vitro studies showed that lisht-induced DTA expression reduced 4 T1 cell viability and induced apoptosis.Furthermore,the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4 T1 tumor xenogratt model,which resulted in excellent antitumor effects,reduced tumor angiogenesis,and no systemic toxicity.The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.

Range and similarity of hollow cathode discharge in argon

Hollow cathode discharge and micro-hollow cathode discharge have numerous applications in the fields of industry,medical treatment,environmental protection,and analytical chemistry.However,many of them lack the typical features of hollow cathode mode,especially the applications at atmospheric pressure.In order to investigate the underlying basic science of hollow cathode discharge,the hollow cathode discharge in argon was studied by experiments.The range for the operation of the hollow cathode mode in the argon-aluminum device was quantitatively determined to be from 0.8 to 4 Torr cm,no matter how small the cathode cavity is.The atmospheric pressure operation of the hollow cathode mode was realised with the aluminum cathode of a 50μm cavity.The hollow cathode discharges were consistent with Townsend similarity law when the anode was very close to the cathode and the value of p·D was chosen at the lower limit of the range for hollow cathode mode.In contrast,if the anode was moved a little bit far from the cathode and the value of p D was significantly increased,the results followed Allis-White scaling law.The reason for the deviation of Allis-White scaling law from Townsend similarity law was given.

Nanoparticle structure transformation of mPEG grafted chitosan with rigid backbone induced by a-cyclodextrin

This paper presented an interesting nanoparticle-based drug delivery system with morphology transition behavior depending on the content of exposed PEG chain on the particle surface, which is adjustable by addition of different amount of cyclodextrin(α-CD). The effect of α-CD inclusion to the self-assembly behavior of methoxy polyethylene glycol(mPEG) grafted chitosan(CS) was studied. The results showed that the mPEG grafted chitosan(mPEG-g-CS) forms self-assembled nanoparticles with either micelle or hollow sphere morphology depending on the ratio of α-CD to mPEG, as characterized by atomic force microscopy(AFM), transmission electron microscopy(TEM), and X-ray diffraction(XRD). Their sizes and zeta potential increased from 257.6 nmto 768.2 nm and from +4.5 mV to +11.6 mV, respectively, with the increasing amount of α-CD. The correlation between zeta potential and particle size of α-CD/mPEG-g-CS nanoparticles indicated varied PEG density on surface of nanoparticles. Based on the above experimental observations, a likely mechanism for the morphological transition of the rod-coil graft copolymer mPEG-g-CS was proposed.

Redox-responsive self-assembly polymeric micelles based on mPEG-β-cyclodextrin and a camptothecin prodrug as drug release carriers

Stimuli-responsive drug delivery systems based on polymeric micelles can achieve controlled drug release to improve the therapeutic outcome and reduce unwanted systematic toxicity and side effects of the cytotoxic drug in chemotherapy but often face challenging synthesis and purification of functionalized biocompatible polymer materials and low drug loading efficiency. In the present study, we reported a novel redox-responsive self-assembly polymeric micelle system, mPEG-β-CD/Ad-SS-CPT, to achieve high loading efficiency and selective delivery of camptothecin(CPT) in a reductive environment inside cancer cells. The host-guest supramolecular micelles utilized a simple β-CD modified PEG, mPEG-β-cyclodextrin(mPEG-β-CD), as the polymeric host with the ease of synthesis and purification. The guest prodrug Ad-SS-CPT contained the disulfide bond as the redox sensitivity group. The selective cleavage of disulfide bond and subsequent drug release in a reductive environment could potentially reduce system toxicity and improve the therapeutic outcome of CPT. In vitro studies showed that the micelles exhibited excellent cytotoxicity against He La cells comparable to the free drug. The host-guest polymeric micelles also showed great potentials for multi-drug co-delivery. Collectively, our current findings provided a general and convenient approach to design drug delivery systems based on stimuli-responsive polymeric micelles for disease treatment.