Nanotechnology-Assisted Co-Delivery of Immunotherapeutic Agents for Targeting Ovarian Cancer: Prospects and Challenges

Background: Ovarian cancer is one of the most lethal gynecologic malignancies, mainly due to late diagnoses and chemoresistance. The immune checkpoint inhibitors and other immunotherapies achieve very low response rates in ovarian cancer. Nanotechnology-assisted co-delivery can helpful by simultaneously delivering multiple therapeutic agents together with their collective advantages. Methods: This review documents recent advances in nanocarrier-based co-delivery of immunotherapeutics for ovarian cancer, including organic (liposomes, Polymeric nanoparticles, dendrimers), inorganic (gold nanoparticles, mesoporous silica nanoparticles, and metal-organic frameworks), and hybrid (polymer-drug conjugates combined with gene vectors, polymer-lipid nanoparticles) nanocarrier systems. Early clinical trial data show that such systems can reprogram the myeloid cells in ovarian cancer. Key co-delivery strategies covered include combinations of chemotherapy with checkpoint inhibitors, cytokines with adjuvants, and gene therapies with conventional drugs. Results: Nanocarrier-based co-delivery enables synergistic therapy by simultaneously targeting tumor cells and the immune microenvironment. The co-delivery of chemotherapeutics with immune checkpoint inhibitors promotes antigen expression by relieving immune suppression within the tumor microenvironment, hence improving the subsequent immune activation while increasing the infiltration of T-cells. Similarly, nanoparticle delivery of immunostimulatory cytokines produces local immune activation with reduced systemic toxicity, and gene-editing nanotherapies have also emerged. Conclusion: Nanotechnology-assisted co-delivery strategies overcome the immunotherapy limitations in ovarian cancer. Preclinical and early clinical outcomes are encouraging, with some challenges in safety, synthesis, and regulatory concerns. Continued innovation in biodegradable nanocarriers and rigorous clinical evaluation are crucial to fully realize the clinical impact in ovarian cancer. Keywords: ovarian cancer, co-delivery, nanotechnology, nanocarriers, immunotherapy