Helicobacter pylori infection is
one of the leading causes of several gastroduodenal diseases, such
as gastritis, peptic ulcer, and gastric cancer. In fact, H. pylori eradication provides a preventive effect
against the incidence of gastric cancer. Amoxicillin is a commonly
used antibiotic for H. pylori eradication.
However, due to its easy degradation by gastric acid, it is necessary
to administer it in a large dosage and to combine it with other antibiotics.
This complexity and the strong side effects of H. pylori eradication therapy often lead to treatment failure. In this study,
the chitosan/poly (acrylic acid) particles co-loaded with superparamagnetic
iron oxide nanoparticles and amoxicillin (SPIO/AMO@PAA/CHI) are used
as drug nano-carriers for H. pylori eradication therapy. In vitro and in vivo results show that the designed SPIO/AMO@PAA/CHI nanoparticles are
biocompatible and could retain the biofilm inhibition and the bactericidal
effect of amoxicillin against H. pylori. Moreover, the mucoadhesive property of chitosan allows SPIO/AMO@PAA/CHI
nanoparticles to adhere to the gastric mucus layer and rapidly pass
through the mucus layer after exposure to a magnetic field. When PAA
is added, it competes with amoxicillin for chitosan, so that amoxicillin
is quickly and continuously released between the mucus layer and the
gastric epithelium and directly acts on H. pylori. Consequently, the use of this nano-carrier can extend the drug
residence time in the stomach, reducing the drug dose and treatment
period of H. pylori eradication therapy.
Despite aggressive multimodality therapy, most neuroblastoma-bearing patients relapse and survival rate remains poor. Exploration of alternative therapeutic modalities is needed. Carbon nanotubes (CNTs), revealing optical absorbance in the near-infrared region, warrant their merits in photothermal therapy. In order to specifically target disialoganglioside (GD2) overexpressed on the surface of neuroblastoma stNB-V1 cells, GD2 monoclonal antibody (anti-GD2) was conjugated to acidified CNTs. To examine the fate of anti-GD2 bound CNTs after incubation with stNB-V1 cells, rhodamine B was labeled on carboxylated CNTs functionalized with and without anti-GD2. Our results illustrated that anti-GD2-linked CNTs were extensively internalized by neuroblastoma cells via GD2-mediated endocytosis. In addition, we showed that anti-GD2 bound CNTs were not ingested by PC12 cells without GD2 expression. After anti-GD2 conjugated CNTs were incubated with neuroblastoma cells for 6 h and endocytosed by the cells, CNT-laden neuroblastoma cells were further irradiated with an 808 nm near-infrared (NIR) laser with intensity ramping from 0.6 to 6 W cm(-2) for 10 min which was then maintained at 6 W cm(-2) for an additional 5 min. Post-NIR laser exposure, and after being examined by calcein-AM dye, stNB-V1 cells were all found to undergo necrosis, while non-GD2 expressing PC12 cells all remained viable. Based on the in vitro study, CNTs bound with anti-GD2 have the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure.
Background
Lung cancer is the leading cause of cancer patient death in the world. There are many treatment options for lung cancer, including surgery, radiation therapy, chemotherapy, targeted therapy, and combined therapy. Despite significant progress has been made in the diagnosis and treatment of lung cancer during the past few decades, the prognosis is still unsatisfactory.
Purpose
To resolve the problem of chemotherapy failure, we developed a magnetite-based nanomedicine for chemotherapy acting synergistically with loco-regional hyperthermia.
Methods
The targeting carrier consisted of a complex of superparamagnetic iron oxide (SPIO) and poly(sodium styrene sulfonate) (PSS) at the core and a layer-by-layer shell with cisplatin (CDDP), together with methotrexate – human serum albumin conjugate (MTX−HSA conjugate) for lung cancer-specific targeting, referred to hereafter as SPIO@PSS/CDDP/HSA−MTX nanoparticles (NPs).
Results
SPIO@PSS/CDDP/HSA−MTX NPs had good biocompatibility and stability in physiological solutions. Furthermore, SPIO@PSS/CDDP/HSA−MTX NPs exhibited a higher temperature increase rate than SPIO nanoparticles under irradiation by a radiofrequency (RF) generator. Therefore, SPIO@PSS/CDDP/HSA−MTX NPs could be used as a hyperthermia inducer under RF exposure after nanoparticles preferentially targeted and then accumulated at tumor sites. In addition, SPIO@PSS/CDDP/HSA−MTX NPs were developed to be used during combined chemotherapy and hyperthermia therapy, exhibiting a synergistic anticancer effect better than the effect of monotherapy.
Conclusion
Both in vitro and in vivo results suggest that the designed SPIO@PSS/CDDP/HSA−MTX NPs are a powerful candidate nanoplatform for future antitumor treatment strategies.
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