Self-assembled Nanoparticles based on Folic Acid Modifi ed Carboxymethyl Chitosan Conjugated with Targeting Antibody

Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldrug and encapsulate within folic acid modified carboxymethylchitosan（FACMCS）nanoparticles through self-assembling.The chemicalstructure,morphology,release and targeting of nanoparticles were characterized by routine detection.It is demonstrated that the mean diameter is about 150 nm,the release rate increases with the decreasing of p H,the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5：2,and nanoparticles can effectively bind onto HL60 cells in vitro.The experimentalresults indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potentialp Hsensitive drug delivery system with leukemic targeting properties.

Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment

Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.

NOVEL pH-SENSITIVE DRUG DELIVERY SYSTEM BASED ON NATURAL POLYSACCHARIDE FOR DOXORUBICIN RELEASE

A novel pH-sensitive nanoparticle drug delivery system (DDS) derived fl om natural polysaccharide pullulan for doxorubicin (DOX) release was prepared.Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups.DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate.This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX.Trans...

Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth syndrome

Barth syndrome（BTHS） is a mitochondrial disorder characterized by cardiomyopathy and skeletal muscle weakness. Disease results from mutations in the tafazzin（TAZ） gene, encoding a phospholipid transacylase. Defective tafazzin activity results in an aberrant cardiolipin（CL） profile. The feasibility of restoring the intracellular CL profile was tested by in vivo administration of exogenous CL in nanodisk（ND） delivery particles. Ninety mg/kg CL（as ND）was administered to doxycycline-inducible taz shRNA knockdown（KD） mice once a week. After 10 weeks of CLND treatment, the mice were sacrificed and tissues harvested. Liquid chromatography-mass spectrometry of extracted lipids revealed that CL-ND administration failed to alter the CL profile of taz KD or WT mice. Thus, although CL-ND were previously shown to be an effective means of delivering CL to cultured cells, this effect does not extend to an in vivo setting. We conclude that CL-ND administration is not a suitable therapy option for BTHS.

Advances in the nanoparticle drug delivery systems of silymarin

The recent advances in nanoscience and nanotechnology have greatly facilitated the development of nanoparticle drug delivery system. A nanoparticle drug delivery system of silymarin will improve its poor solubility in water and oil, thus enhancing its bioavailability. A variety of nanoparticle formulations of silymarin such as solid lipid nanoparticles, microemulsion and self-emulsifying drug delivery system, and liposomes have been extensively investigated. This paper reviews the advances of these formulations on their preparation and characterization, absorption and bioavailability, as well as in vivo and in vitro studies, in order to provide an assessment of current research for further pharmaceutical studies of silymarin.

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.

Engineering of drug nanoparticles by HGCP for pharmaceutical applications

This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nanoparticles, which was carried out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxime Axetil (CFA) particles, 200–400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), and 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation and drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing and the ease of scaling-up.

Redox-responsive polymer prodrug/AgNPs hybrid nanoparticles for drug delivery

A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[（2-（（2-（（camptothecin）-oxy）ethyl）disulfanyl）ethylmethacrylate）-co-（2-（D-galactose）methylmethacryl-ate）]（P（MACPTS-co-MAGP）） and AgNPs is developed to deliver the anti-cancer drug camptothecin（CPT） and monitor the drug release by the recovery of the fluorescence of CPT. CPT is linked to the polymer sidechains via a redox-responsive disulfide bond, attaching on the surface of AgNPs and leading to the quenching of CPT fluorescence（ ＂off＂ state） due to the nanoparticle surface energy transfer（NSET） effect.Upon the exposure to glutathione（GSH）, the disulfide bond is cleaved to release CPT, resulting in the recovery of the fluorescence of CPT（＂on＂ state）. The system offers a platform to track the CPT delivery and releasing in real time

Editorial for biomimetic nanoparticles for drug delivery

The origins of controlled release drug delivery could be dated back to the 1950s.The Spansule technology was developed to deliver a drug for 12 h in 1952.Compared with taking a drug every 6 h or every8 h,twice-a-day formulation was revolutionary in improving the patients’compliance and convenience1.Since then,advances in drug delivery technologies have introduced numerous formulations

Molecular dynamics simulation of diffusion of nanoparticles in mucus

The rapid diffusion of nanoparticles （NPs） through mucus layer is critical for efficient transportation of NPs-loaded drug delivery system. To understand how the physical and surface properties of NPs affect their diffusion in mucus, we have developed a coarse-grained molecular dynamics model to study the diffusion of NPs in modeled mucus layer. Both steric obstruction and hydrodynamic interaction are included in the model capable of capturing the key characteristics of NPs＇ diffusion in mucus. The results show that both particle size and surface properties significantly affect the diffusivities of NPs in mucus. Furthermore, we find rodlike NPs can gain a higher diffusivity than spherical NPs with the same hydrodynamic diameter. In addition, the disturbed environment can enhance the diffusivity of NPs. Our findings can be utilized to design mucus penetrating NPs for targeted drug delivery system.

Editor Profile: Guest Editor of Special Issue on Biomimetic Nanoparticles for Drug Delivery

Dr.Jianxin Wang is a professor of pharmaceutics at Fudan University,School of Pharmacy.He received his Ph.D.in pharmaceutics from West China University of Medical Sciences in 1999.He worked for Shanghai Institute of Chinese Materia Medica from July 1999 to April 2005.Dr.Wang became a faculty member of School of Pharmacy,Fudan University in 2005.He worked as a visiting scholar in the College of Pharmacy,

Cisplatin-loaded Poly(L-glutamic acid)-g-Methoxy Poly(ethylene glycol) Nanoparticles as a Potential Chemotherapeutic Agent against Osteosarcoma

Herein, cisplatin-loaded poly（L-glutamic acid）-g-methoxy poly（ethylene glycol） nanoparticles were evaluated as a potential chemotherapeutic agent against osteosarcoma by using alone or with an i RGD（internalizing RGD, CRGDKDPDC）. The release rate of platinum from the cisplatin-loaded nanoparticles CDDP/PLG160-g-m PEG2K（CDDP-NPs） accelerated with the increase of the acidity of the environment. In vitro test demonstrated that CDDP-NPs could inhibit the proliferation of MNNG/Hos osteosarcoma cells with IC50（72 h） of 12.2 μg·mL^-1. In vivo test for MNNG/Hos osteosarcoma tumor bearing mice exhibited that CDDP-NPs had comparable or slightly higher efficacy but significantly lower side effects in comparison with free CDDP. The coadministration of i RGD could further enhance the anticancer efficacy of CDDP-NPs against MNNG/Hos osteosarcoma without bringing obvious side effects. Therefore, CDDP-NPs using alone or with iRGD have great potential for the treatment of osteosarcoma.

Amphiphilic poly(ethylene glycol)-b-poly(ethylene brassylate)copolymers: One-pot synthesis, self-assembly, and controlled drug release

A set of amphiphilic poly（ethylene glycol）-b-poly（ethylene brassylate）（PEG-b-PEB） copolymers based on the PEB hydrophobic block was first synthesized by ring-opening polymerization of ethylene brassylate with an organic catalyst. The EB/PEG molar ratios and reaction times were adjusted to achieve different chain lengths of PEB. Block copolymers that were characterized by1 H NMR and GPC could selfassemble into multimorphological aggregates in aqueous solution, which were characterized by DLS and TEM. The hydrophobic doxorubicin（DOX） was chosen as a drug model and successfully encapsulated into the nanoparticles. The release kinetics of DOX were investigated.

Effect of chirality on conformation and cellular uptake of poly(S-(o-nitrobenzyl)-L,D-cysteine) polypeptides

A series of poly（S-（o-nitrobenzyl）-L,D-cysteine） polypeptides with different chirality was synthesized and their molecular structures,secondary conformations,drug release and biological properties were thoroughly investigated.The chirality of the polypeptides had effect on secondary conformations and the cellular uptake behavior of the related nanoparticles.