Biomimetic nanomedicine cocktail enables selective cell targeting to enhance ovarian Cancer chemo- and immunotherapy.

Ovarian cancer is one of the deadliest cancers, and combined chemo- and immunotherapies are potential strategies to combat it. However, the anti-cancer efficacy of the combined therapies may be limited by the non-selective co-delivery of chemotherapy and immunotherapy. Herein, a combined chemo- and immunotherapy is designed to selectively target ovarian tumor (ID8) cells and dendritic cells (DCs) using ID8 cell membrane (IM) and bacterial outer membrane vesicles (OMVs), respectively. Doxorubicin (DOX) and Ovalbumin (OVA) peptide (OVA257-264) are chosen as model chemotherapy and immunotherapy agents, respectively. A DNA nanocube capable of easily loading DOX or OVA257-264 is chosen as the carrier. Firstly, the DNA nanocube is used to load DOX or OVA257-264 to prepare cube-DOX or cube-OVA. This nanocube was then encapsulated with IM to form IM@Cube-DOX and with OMV to form OMV@Cube-OVA. IM@Cube-DOX can be selectively taken up by ID8 cells, leading to effective cell killing, while OMV@Cube-OVA targets and activates DC2.4 cells in vitro. Both IM@Cube-DOX and OMV@Cube-OVA show increased accumulation at ID8 tumors in C57BL/6 mice. Combined IM@Cube-DOX + OMV@Cube-OVA therapy demonstrates better anti-tumor efficacy than non-selective delivery methods such as OMV@(Cube-DOX + Cube-OVA) or IM@(Cube-DOX + Cube-OVA) in ID8-OVA tumor-bearing mice. In conclusion, this study demonstrates a biomimetic delivery strategy that enables selective drug delivery to tumor cells and DCs, thereby enhancing the anti-tumor efficacy of combined chemo- and immunotherapy through the selective delivery strategy.

A macrophage plasma membrane-coated and DNA structured nanomedicine targets to alleviate rheumatoid arthritis via dual inhibition to TNF-α and NF-κB.

High heterogenicity of rheumatoid arthritis (RA) leads to poor response in many patients. Combined therapies that simultaneously inhibit multiple proinflammatory targets may improve anti-RA efficacy. However, which monotherapies to combine and how to achieve the combination are critical issues. Here, we design a macrophage plasma membrane-coated and DNA structured nanomedicine to achieve a dual inhibitory therapy to Tumor necrosis factor alpha (TNF-α) and NF-κB. An anti-NF-κB decoy oligodeoxynucleotides (dODN) is first conjugated to a DNA cage with precise numbers and locations (Cage-dODN). Meanwhile, an anti-TNF-α siRNA is anchored to extracted macrophage plasma membrane (siRNA@M). Subsequently, siRNA@M is used to encapsulate Cage-dODN to fabricate siRNA@M(Cage-dODN) (siMCO). The size and zeta potential of siMCO are 63.1 ± 15.7 nm and -20.7 ± 3.8 mV respectively. siMCO shows increased intracellular uptake by inflamed macrophages and enhanced accumulation in inflamed mouse paws. siMCO also reduces pro-inflammatory factors at genetic and protein levels, alleviates arthritic symptoms, and shows no influence to major blood components. These results show that siMCO is a potential targeted, efficient, and safe dual inhibitory therapy for the treatment of inflammatory arthritis. The macrophage plasma membrane can be utilized to improve the targeting, stability, and efficacy of DNA structured nanomedicines.