Optimized Cationic Lipid-assisted Nanoparticle for Delivering CpG Oligodeoxynucleotides to Treat Hepatitis B Virus Infection.

PURPOSE: Hepatitis B virus (HBV) infection is such a global health problem that hundreds of millions of people are HBV carriers. Current anti-viral agents can inhibit HBV replication, but can hardly eradicate HBV. Cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are an adjuvant that can activate plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) to induce therapeutic immunity for HBV eradication. However, efficient delivery of CpG ODNs into pDCs and cDCs remains a challenge. In this study, we constructed a series of cationic lipid-assisted nanoparticles (CLANs) using different cationic lipids to screen an optimal nanoparticle for delivering CpG ODNs into pDCs and cDCs. METHODS: We constructed different CLANCpG using six cationic lipids and analyzed the cellular uptake of different CLANCpG by pDCs and cDCs in vitro and in vivo, and further analyzed the efficiency of different CLANCpG for activating pDCs and cDCs in both wild type mice and HBV-carrier mice. RESULTS: We found that CLAN fabricated with 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP) showed the highest efficiency for delivering CpG ODNs into pDCs and cDCs, resulting in strong therapeutic immunity in HBV-carrier mice. By using CLANCpG as an immune adjuvant in combination with the injection of recombinant hepatitis B surface antigen (rHBsAg), HBV was successfully eradicated and the chronic liver inflammation in HBV-carrier mice was reduced. CONCLUSION: We screened an optimized CLAN fabricated with DOTAP for efficient delivery of CpG ODNs to pDCs and cDCs, which can act as a therapeutic vaccine adjuvant for treating HBV infection.

Polyphosphoester-Based Nanocarrier for Combined Radio-Photothermal Therapy of Breast Cancer.

Recently, clinical research on tumor therapy has gradually shifted from traditional monotherapy toward combination therapy as tumors are complex, diverse, and heterogeneous. Combination therapy may be essential for achieving the optimized treatment efficacy of tumors through distinct tumor-inhibiting mechanisms. At the same time, nanocarriers are emerging as an excellent strategy for delivering both drugs simultaneously. This work presents utilization of a polyphosphoester-based nanocarrier (NPIR/Cur) to achieve the codelivery of hydrophobic photothermal agent IR-780 and radiosensitizer curcumin (Cur). The IR-780 and curcumin coencapsulated NPIR/Cur exhibited adequate drug loading, a prolonged blood half-life, enhanced passive tumor homing, and improved curcumin bioavailability as well as combined therapeutic functions. Briefly, NPIR/Cur could not only achieve effective thermal ablation through the conversion of near-infrared light to heat, but also give rise to a significant boosted local radiation dose to trigger promoted radiation damages, thus resulting in enhanced tumor cell growth inhibition. In conclusion, the as-prepared NPIR/Cur manifested excellent performance in facilitating combined photothermal and radiation therapy, thus expanding the application range of PPE-based carriers in nanomedicine, and also prompting exploration of their potential for other effective combination therapies.