Macrophage-hitchhiked arsenic/AB bionic preparations for liver cancer.

Macrophage-hitchhiked arsenic/AB bionic preparations were developed to improve the therapeutic effect on liver cancer by means of the tumor-targeting ability of macrophages in vivo. In vitro and in vivo cellular uptake assays demonstrated that arsenic/AB, with negatively charged particles of around 100-200 nm size, could hitchhike to macrophages. Dissolution experiments of arsenic/AB showed that arsenic/AB could delay the release of arsenic and ensure the safety of macrophages during its transport. Histological examination confirmed the safety of the preparations for major organs. In vivo distribution experiment showed that the arsenic/AB bionic preparations could rapidly accumulate in tumors, and in vivo treatment experiment showed a significant tumor inhibition of arsenic/AB. The therapeutic mechanism of liver cancer might be that the arsenic/AB bionic preparations could inhibit tumor growth by reducing inflammatory response and inhibiting CSF1 secretion to block CSF1R activation to induce more differentiation of tumor-associated macrophages (TAMs) towards the anti-tumor M1 phenotype. Therefore, we concluded that the arsenic/AB bionic preparations could improve the distribution of arsenic in vivo by hitchhiking on macrophages as well as make it have tumor targeting and deep penetration abilities, thus increasing the therapeutic effect of arsenic on liver cancer with reduced side effects.

Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells.

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

[Preparation and in vitro evaluation of arsenic trioxide glioma targeting drug delivery system loaded by PAMAM dendrimers co-modified with RGDyC and PEG].

Arsenic trioxide (ATO) is an effective component of traditional Chinese medicine arsenic. The existing studies have shown its good inhibition and apoptosis ability on a variety of tumours. However, its toxicity and difficulties in the permeability into the blood brain barrier (BBB) has the limitation in the application of glioma treatment. Polyamide-amine dendrimer (PAMAM) is a synthetic polymer with many advantages, such as a good permeability, stability and biocompatibility. Additionally, the 5th generation of PAMAM is an ideal drug carrier due to its three-dimensional structure. In this study, the 5th generation of PAMAM co-modified with RGDyC and PEG, then confirmed by ¹H-NMR. The average particle size of nanoparticles was about 20 nm according to the nanoparticle size-potential analyser and transmission electron microscopy. in vitro release showed that the nanocarrier not only has the sustained release effect, but also some pH-sensitive properties. The cell results showed that PAMAM co-modified with RGDyC and PEGAM has a lower cytotoxicity than the non-modified group in vitro. Accordingly, the drug delivery system has a better anti-tumour effect across the blood brain barrier (BBB) in vitro, which further proves the tumour targeting of RGDyC.

Targeted drug delivery for tumor therapy inside the bone marrow.

Bone marrow is the primary hematopoietic organ, which is involved in multiple malignant diseases including acute and chronic leukemia, multiple myeloma, myelodysplastic syndromes, and bone metastases from solid tumors. These malignancies affect normal homeostasis and reshape the bone marrow microenvironment. There are limited treatment options for them because of their inevitable aggravation. The current systemic administration of anticancer agents is difficult to achieve ideal therapeutic dose to suppress tumor growth at bone marrow diseased sites, and is always associated with a high incidence of relapse and severe side effects. The limitations of current treatments urge scientists to develop bone marrow targeted drug delivery systems intended for the treatment of diseased bone marrow, which can improve the efficacy of therapeutic agents and reduce their dose-limiting systemic side effects on healthy tissues. In this review we first present the current opinions on bone marrow vasculature, as well as the molecular and structural interactions between tumor cells and the diseased bone marrow. In the second part, we highlight the different design rationales and strategies of bone marrow delivery systems and their therapeutic applications for the treatment of malignancies inside the bone marrow.