Search for: All records

Ovarian cancer is especially deadly, challenging to treat, and has proven refractory to known immunotherapies. Cytokine therapy is an attractive strategy to drive a proinflammatory immune response in immunologically cold tumors such as many high grade ovarian cancers; however, this strategy has been limited in the past due to severe toxicity. We previously demonstrated the use of a layer‐by‐layer (LbL) nanoparticle (NP) delivery vehicle in subcutaneous flank tumors to reduce the toxicity of interleukin‐12 (IL‐12) therapy upon intratumoral injection. However, ovarian cancer cannot be treated by local injection as it presents as dispersed metastases. Herein, we demonstrate the use of systemically delivered LbL NPs using a cancer cell membrane‐binding outer layer to effectively target and engage the adaptive immune system as a treatment in multiple orthotopic ovarian tumor models, including immunologically cold tumors. IL‐12 therapy from systemically delivered LbL NPs shows reduced severe toxicity and maintained anti‐tumor efficacy compared to carrier‐free IL‐12 or layer‐free liposomal NPs leading to a 30% complete survival rate.

Zwitterionic surfaces are increasingly explored as antifouling coatings due to their propensity to resist protein, bacterial, and cell adhesion and are typically applied as polymeric systems. Here, the self‐assembly of strongly interacting small molecule amphiphiles is reported to produce nanoribbons for antifouling applications. Synthesized amphiphiles spontaneously form micrometers‐long nanoribbons with nanometer‐scale cross‐sections and intrinsically display a dense coating of zwitterionic moieties on their surfaces. Substrates coated with nanoribbons demonstrate concentration‐dependent thicknesses and near superhydrophilicity. These surface coatings are then probed for antifouling properties and substantial reductions are demonstrated in protein adsorption, bacterial biofilm formation, and cell adhesion relative to uncoated controls. Harnessing cohesive small molecule self‐assembling nanomaterials for surface coatings offers a facile route to effective antifouling surfaces.

Advanced staged high‐grade serous ovarian cancer (HGSOC) is the leading cause of gynecological cancer death in the developed world, with 5‐year survival rates of only 25–30% due to late‐stage diagnosis and the shortcomings of platinum‐based therapies. A Phase I clinical trial of a combination of free cisplatin and poly(ADP‐ribose) polymerase inhibitors (PARPis) showed therapeutic benefit for HGSOC. In this study, we address the challenge of resistance to platinum‐based therapy by developing a targeted delivery approach. Novel electrostatic layer‐by‐layer (LbL) liposomal nanoparticles (NPs) with a terminal hyaluronic acid layer that facilitates CD44 receptor targeting are designed for selective targeting of HGSOC cells; the liposomes can be formulated to contain both cisplatin and the PARPi drug within the liposomal core and bilayer. The therapeutic effectiveness of LbL NP‐encapsulated cisplatin and PARPi alone and in combination was compared with the corresponding free drugs in luciferase and CD44‐expressing OVCAR8 orthotopic xenografts in female nude mice. The NPs exhibited prolonged blood circulation half‐life, mechanistic staged drug release and targeted codelivery of the therapeutic agents to HGSOC cells. Moreover, compared to the free drugs, the NPs resulted in significantly reduced tumor metastasis, extended survival, and moderated systemic toxicity.