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.
Cancer is a dynamic disease characterized by its heterogeneous nature. This heterogeneity results in critical problems that interfere with the eradication of cancer tumors such as multidrug resistance, drug efflux capacity, narrow therapeutic window, and undesired side effects. Nanomedicine has introduced new platforms for drug delivery to enhance therapeutic efficiency of anticancer drugs. In addition to drug delivery, nanocarriers such as liposomes, carbon nanotubes, quantum dots, polymeric nanoparticles, dendrimers, and metallic nanoparticles can be designed for detection, diagnosis, and treatment. Recent studies support the idea that a combination of two or more nanoparticle‐mediated therapies can result in a synergistic therapeutic outcome to improve current cancer treatments. In this progress report, recent advances in nanoparticles‐based combination therapies are discussed. A brief overview of the complexity of cancer tumor's microenvironment is presented, followed by discussion of combinatorial therapies categorized based on chemotherapeutic agents, nucleic acid or therapeutic proteins, energy‐based therapies and imaging techniques for theranostic application. Different nanotechnological platforms are developed for combination therapy as tools with a great potential to tackle the most critical issues of current cancer treatments. A deeper understanding of these nanotechnologies and their possible long‐term effects in biological systems is needed for further clinical translation.
more » « less- NSF-PAR ID:
- 10372258
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Therapeutics
- Volume:
- 2
- Issue:
- 11
- ISSN:
- 2366-3987
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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