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Engineering Nanoparticles for Gynecologic Cancer Therapy
Amanda M Murray1, Kelsey L Swingle1, Michael J Mitchell1,2,3,4,5,6,7
1Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 S 33rd Street, Philadelphia, Pennsylvania 19104, United States.
Abstract:
The significant morbidity and mortality of gynecologic cancers places a substantial burden on global healthcare and creates an urgent need for new treatment modalities. Here, we explore the emerging role of nanoparticles in treating gynecologic cancers, specifically ovarian, cervical, and endometrial cancers. These diseases are often diagnosed after they have metastasized, developed multidrug resistance, and formed immunosuppressive tumor microenvironments, hampering the effectiveness of traditional debulking surgery and chemotherapy. We first discuss the gynecologic cancer-specific barriers to nanoparticle drug delivery, including systemic and off-target toxicity, peritoneal fluid shear and convective forces, stromal fibrosis, and immunosuppressive tumor microenvironments. We then comprehensively analyze how various nanoparticle drug delivery platforms, such as liposomes, ionizable lipid nanoparticles, and layer-by-layer nanoparticles, have been engineered preclinically to selectively target tumor cells and increase retention within tumor lesions. Additionally, we examine the application of nanoparticles in delivering nucleic acids and immunotherapies, which can heat up immunologically cold tumors and tumor microenvironments to restore antitumor immune function. Despite promising preclinical results, additional efforts are needed to optimize nanoparticle design and ensure safe and effective translation into the clinic for all gynecologic cancers, and we conclude by discussing potential solutions to these barriers. Overall, this review explores the latest preclinical studies and emerging frontiers in nanoparticle therapies for gynecologic cancers, with a focus on efforts to overcome the disease-specific delivery challenges to effectively treat these lethal diseases.
Insights
Nanoparticles offer promising new treatments for gynecologic cancers like ovarian, cervical, and endometrial cancers. This review details nanoparticle delivery strategies and challenges for overcoming drug resistance and improving patient outcomes.
Area of Science:
- Oncology
- Nanotechnology
- Biomedical Engineering
Background:
- Gynecologic cancers (ovarian, cervical, endometrial) present significant global health challenges due to high morbidity and mortality.
- Late-stage diagnosis, metastasis, multidrug resistance, and immunosuppressive tumor microenvironments limit traditional treatments.
Purpose of the Study:
- To explore the potential of nanoparticles as a novel therapeutic modality for gynecologic cancers.
- To analyze nanoparticle drug delivery challenges and engineered solutions specific to gynecologic malignancies.
Main Methods:
- Review of preclinical studies on nanoparticle drug delivery platforms (liposomes, ionizable lipid nanoparticles, layer-by-layer nanoparticles).
- Analysis of nanoparticle applications in delivering nucleic acids and immunotherapies.
- Examination of strategies to overcome gynecologic cancer-specific delivery barriers.
Main Results:
- Engineered nanoparticles demonstrate preclinical efficacy in targeting tumor cells and enhancing retention.
- Nanoparticle-delivered nucleic acids and immunotherapies show potential to re-activate antitumor immune responses.
- Strategies are being developed to address toxicity, peritoneal fluid dynamics, fibrosis, and immunosuppression.
Conclusions:
- Nanoparticle-based therapies hold significant promise for treating gynecologic cancers, particularly in overcoming drug resistance and immune evasion.
- Further optimization of nanoparticle design and rigorous clinical translation are crucial for widespread application.
- Addressing disease-specific delivery challenges is key to realizing the full therapeutic potential of nanomedicine in gynecologic oncology.
