Chitosan is a biodegradable natural polymer with many advantages such as nontoxicity, biocompatibility, and biodegradability. It can be applied in many fields, especially in medicine. As a delivery carrier, it has great potential and cannot be compared with other polymers. Chitosan is extremely difficult to solubilize in water, but it can be solubilized in acidic solution. Its insolubility in water is a major limitation for its use in medical applications. Chitosan derivatives can be obtained by chemical modification using such techniques as acylation, alkylation, sulfation, hydroxylation, quaternization, esterification, graft copolymerization, and etherification. Modified chitosan has chemical properties superior to unmodified chitosan. For example, nanoparticles produced from chitosan derivatives can be used to deliver drugs due to their stability and biocompatibility. This review mainly focuses on the properties of chitosan, chitosan derivatives, and the origin of chitosan-based nanoparticles. In addition, applications of chitosan-based nanoparticles in drug delivery, vaccine delivery, antimicrobial applications, and callus and tissue regeneration are also presented. In summary, nanoparticles based on chitosan have great potential for research and development of new nano vaccines and nano drugs in the future.

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R-spondin3 (RSPO3), an activator of Wnt/β-catenin signaling, plays a key role in tumorigenesis of various cancers, but its role in choriocarcinoma remains unknown. To investigate the effect of RSPO3 on the tumor growth of choriocarcinoma JEG-3 cells, the expression of RSPO3 in human term placenta was detected, and a stable RSPO3-overexpressing JEG-3 cell line was established via lentivirus-mediated transduction. The expression of biomarkers involved in tumorigenicity was detected in the RSPO3-overexpressing JEG-3 cells, and cell proliferation, invasion, migration, and apoptosis were investigated. Moreover, soft agar clonogenic assays and xenograft tumorigenicity assays were performed to assess the effect of RSPO3 on tumor growth in vitro and in vivo. The results showed that RSPO3 was widely expressed in human term placenta and overexpression of RSPO3 promoted the proliferation and inhibited the migration, invasion, and apoptosis of the JEG-3 cells. Meanwhile, RSPO3 overexpression promoted tumor growth both in vivo and in vitro. Further investigation showed that the phosphorylation levels of Akt, phosphatidylinositol 3-kinase (PI3K), and ERK as well the expression of β-catenin and proliferating cell nuclear antigen (PCNA) were increased in the RSPO3-overexpressing JEG-3 cells and tumor xenograft. Taken together, these data indicate that RSPO3 promotes the tumor growth of choriocarcinoma via Akt/PI3K/ERK signaling, which supports RSPO3 as an oncogenic driver promoting the progression of choriocarcinoma.

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Background There has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents. To elevate the potential of O-2ʹ-Hydroxypropyl trimethyl ammonium chloride chitosan (O-2ʹ-HACC) as an adjuvant and mucosal immune delivery carrier for DNA vaccine, we prepared the O-2ʹ-HACC loaded with Newcastle disease virus (NDV) F gene plasmid DNA and C3d6 molecular adjuvant (O-2ʹ-HACC/pFDNA microparticles). Results The O-2ʹ-HACC/pFDNA exhibited a regular spherical morphology with a particle size of 202.3 ± 0.52 nm, a zeta potential of 50.8 ± 8.21 mV, encapsulation efficiency of 90.74 ± 1.10%, and a loading capacity of 49.84 ± 1.20%. The plasmid DNA could be sustainably released from the O-2ʹ-HACC/pFDNA after an initial burst release. Intranasal vaccination of chickens immunized with O-2ʹ-HACC/pFDNA not only induced higher anti-NDV IgG and sIgA antibody titers but also significantly promoted lymphocyte proliferation and produced higher levels of IL-2, IL-4, IFN-γ, CD4+, and CD8 + T lymphocytes compared with the NDV commercial live attenuated vaccine. Intranasal delivery of the O-2ʹ-HACC/pFDNA enhanced humoral, cellular, and mucosal immune responses and protected chickens from the infection of highly virulent NDV compared with the intramuscular delivery. Conclusions Collectively, our findings indicated that the O-2ʹ-HACC could be used as a vaccine adjuvant and delivery system for mucosal immunity and have an immense application promise. Graphic Abstract

Regorafenib (REGO) is a synthetic oral multi-kinase inhibitor with potent antitumor activity. In this study, we investigate the molecular mechanisms by which REGO induces apoptosis. REGO induced cytotoxicity, inhibited the proliferation and migration ability of cells, and induced nuclear condensation, and reactive oxygen species (ROS)-dependent apoptosis in cancer cells. REGO downregulated PI3K and p-AKT level, and prevented FOXO3a nuclear export. Most importantly, AKT agonist (SC79) not only inhibited REGO-induced FOXO3a nuclear localization and apoptosis but also restored the proliferation and migration ability of cancer cells, further demonstrating that REGO prevented FOXO3a nuclear export by deactivating PI3K/AKT. REGO treatment promotes Bim expression via the FOXO3a nuclear localization pathway following PI3K/AKT inactivation. REGO induced Bim upregulation and translocation into mitochondria as well as Bim-mediated Bax translocation into mitochondria. Fluorescence resonance energy transfer (FRET) analysis showed that REGO enhanced the binding of Bim to Bak/Bax. Knockdown of Bim, Bak and Bax respectively almost completely inhibited REGO-induced apoptosis, demonstrating the key role of Bim by directly activating Bax/Bak. Knockdown of Bax but not Bak inhibited REGO-induced Drp1 oligomerization in mitochondria. In conclusion, our data demonstrate that REGO promotes apoptosis via the PI3K/AKT/FOXO3a/Bim-mediated intrinsic pathway.

Different natural and synthetic biodegradable polymers have been used in vaccine formulations as adjuvant and delivery system but have faced various limitations. Chitosan is a new delivery system with the potential to improve development of nano vaccines and drugs. However, chitosan is only soluble in acidic solutions of low concentration inorganic acids such as dilute acetic acid and dilute hydrochloric acid and in pure organic solvents, which greatly limits its application. Chemical modification of chitosan is an important way to improve its weak solubility. Quaternized chitosan not only retains the excellent properties of chitosan, but also improves its water solubility for a wider application. Recently, quaternized chitosan nanoparticles have been widely used in biomedical field. This review focuses on some quaternized chitosan nanoparticles, and points out the advantages and research direction of quaternized chitosan nanoparticles. As shown by the applications of quaternized chitosan nanoparticles as adjuvant and delivery carrier in vaccines, quaternized chitosan nanoparticles have promising potential in application for the development of nano vaccines in the future.

Nasal administration for vaccine delivery is a novel non-invasive vaccine administration approach that can induce local or systemic immune responses and overcome the disadvantages caused by traditional injectable administration. However, mucosal vaccine and adjuvant delivery systems with sustained-release ability and enhanced immune effects at mucosal sites have still been highly demanded. In this work, N-2-hydroxypropyl trimethyl ammonium chloride chitosan/N,O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) with excellent mucosal absorption, high drug loading capacity, and enhanced immune responses were prepared by the ionic cross-linking method. To evaluate the potential capacity of the N-2-HACC/CMCS NPs as a vaccine adjuvant and the molecular mechanism for the induction of enhanced mucosal and systemic immune responses, bovine serum albumin (BSA) was employed as a general model antigen and loaded into the N-2-HACC/CMCS NPs to prepare a BSA-loaded N-2-HACC/CMCS adjuvant vaccine (N-2-HACC/CMCS/BSA NPs). It was well demonstrated that the N-2-HACC/CMCS/BSA NPs with great biostability and mucosal absorption could effectively promote the proliferation of lymphocytes and the secretion of related pro-inflammatory factors, resulting in the stimulation of specific mucosal and systemic immune responses. This study revealed that the chitosan-based nano-delivery system can act as the mucosal vaccine adjuvant and possesses great promise in viral infectious diseases and immunization therapy.