A comparison study between lycobetaine-loaded nanoemulsion and liposome using nRGD as therapeutic adjuvant for lung cancer therapy.

To achieve tumor-selective drug delivery, various nanocarriers have been explored using either passive or active targeting strategies. Despite the great number of studies published annually in the field, only nanocarriers using approved excipients reach the clinical stage. In our study, two classic nanoscale formulations, nanoemulsion (NE) and liposome (Lipo) were selected for the encapsulation of lycobetaine (LBT). To improve the lipid solubility of LBT, oleic acid (OA) was used to complex (LBT-OA) with lycobetaine (LBT). Besides, PEGylated lecithin was used to enhance the circulation time. The release behaviors of LBT from non-PEGylated and PEGylated NE and Lipo were compared. PEGylated LBT-OA loaded Lipo (LBT-OA-PEG-Lipo) exhibited a sustained release rate pattern, and in vivo pharmacokinetic profiles showed the extended circulation compared nanoemlusions. Besides, LBT-OA-PEG-Lipo showed an enhanced anti-tumor effect in the mice xenograft lung carcinoma model. Moreover, a multi-target peptide nRGD was co-administered as a therapeutic adjuvant with LBT-OA loaded formulations, which demonstrated improved tumor penetration and enhanced extravasation of formulations. Also, co-administration of nRGD significantly improved the in vivo antitumor efficacy of different formulations, likely due to the depletion of tumor-associated macrophages (TAMs). Thus, LBT-OA-PEG-Lipo+nRGD may represent a promising strategy for cancer chemotherapy against lung carcinoma.

Development a hyaluronic acid ion-pairing liposomal nanoparticle for enhancing anti-glioma efficacy by modulating glioma microenvironment.

Glioma, one of the most common brain tumors, remains a challenge worldwide. Due to the specific biological barriers such as blood-brain barrier (BBB), cancer stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then, these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which showed near-spherical morphology with an average size of 155.8 nm and uniform distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor, which is over-expressed on the surface of tumor cells, other associated cells (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma efficacy and mechanisms in vivo and in vitro. The strong anti-glioma efficacy could attribute to the accumulation in glioma site and the regulation of tumor microenvironment with depletion of TAMs, inhibition of VMs, and elimination of CSCs.

A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus.

A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N-terminal myristoylated preS1/21-47 (preS1/21-47(myr)) of hepatitis B virus was successfully developed. The study aimed to elucidate the cellular uptake mechanism of preS1/21-47(myr) modified PEG-Lip (preS1/21-47(myr)-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47(myr)-PEG-Lip in Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47(myr)-PEG-Lip was effectively taken up by hepatogenic cells (including primary hepatocytes and liver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing mice, preS1/21-47(myr)-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47(myr)-PEG-Lip in hepatic tumor. Furthermore, the antitumor effect of preS1/21-47(myr)-PEG-Lip loaded with paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation, no acute systemic toxicity and immunotoxicity were observed after intravenous injection of preS1/21-47(myr)-PEG-Lip. No liver toxicity was observed despite the dramatic increase of preS1/21-47(myr)-PEG-Lip in liver. Taken together, preS1/21-47(myr)-PEG-Lip represents a promising carrier system for targeted liver disease therapy and imaging.