Thermosensitive Exosome–Liposome Hybrid Nanoparticle‐Mediated Chemoimmunotherapy for Improved Treatment of Metastatic Peritoneal Cancer

Abstract

Metastatic peritoneal carcinoma (mPC) is a deadly disease without effective treatment. To improve treatment of this disease, a recently developed hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as the standard of care. However, the efficacy of this approach is limited by inefficient drug penetration and rapidly developed drug resistance. Herein, a nanotechnology approach is reported that is designed to improve drug delivery to mPC and to augment the efficacy of HIPEC through delivery of chemoimmunotherapy. First, the drug delivery efficiency of HIPEC is determined and it is found that chemotherapy agents cannot be efficiently delivered to large tumors nodules. To overcome the delivery hurdle, genetically engineered exosomes‐thermosensitive liposomes hybrid NPs, or gETL NPs, are then synthesized, and it is demonstrated that the NPs after intravenous administration efficiently penetrates into mPC tumors and releases payloads at the hypothermia condition of HIPEC. Last, it is shown that, when granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and docetaxel are co‐delivered, gETL NPs effectively inhibit tumor development and the efficacy is enhanced when HIPEC is co‐administered. The study provides a strategy to improve drug delivery to mPCs and offers a promising approach to improve treatment of the disease through combination of locoregional delivery of HIPEC and systemic delivery of chemoimmunotherapy via gETL NPs.

Advances in Lipid-Based Nanoparticles for Cancer Chemoimmunotherapy

“…The contemporaneous administration of OXA and CLANs IDO1 could achieve synergetic antitumor effects via promoting DC maturation, increasing tumor-infiltrating T lymphocytes as well as decreasing the number of regulatory T cells in a subcutaneous colorectal tumor model. Recently, a novel hybrid nanoparticle was designed and used for the codelivery of GM-CSF and DTX in metastatic peritoneal carcinoma (mPC) therapy [ 143 ]. This hybrid nanoparticle was formed by genetically engineered exosomes and thermosensitive liposomes (gETL NPs), as shown in Figure 8 .…”

“… Schematic of the synthesis and application of genetically engineered exosomes and thermosensitive liposomes for the treatment of metastatic peritoneal carcinoma. Adapted from [ 143 ], Advanced Science, 2020. gETL NPs, genetically engineered exosomes-thermosensitive liposomes hybrid nanoparticles; HIPEC, hyperthermic intraperitoneal chemotherapy; TAMs, tumor-associated macrophages; gExos, gExos, genetically engineered exosomes; TLs, thermosensitive liposomes; MPS, mononuclear phagocytic system. …”

Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets

“…Emerging bio-nanotechnologies offer promising advances in diagnostics and therapy 215 . For example, hybrid nanosystems based on genetically engineered exosomes and thermosensitive liposomes are a novel strategy to improve delivery efficacy 216 . Additionally, drug loading and delivery efficiency can be improved through the design of exosome-like nanovesicles and membrane-camouflaged nanoparticles 217 .…”

Nanoparticle-mediated synergistic chemoimmunotherapy for tailoring cancer therapy: recent advances and perspectives

“…The application and manipulation of biomimetic NPs indicate promising role in CIT such as cellular or molecular agents including high-density lipoproteins (HDL), low-density lipoproteins (LDL) [ 137 ], albumin [ 138 ], and exosome [ 139 ], therefore they can emerge predominant potential in CIT perspective. Likewise, some factors, such as biocompatibility, biodegradability, stability in favor of long-term storage, and intended release profile of payloads and delivery of them to target and administration route, should be considered when choosing a good nanocarrier [ 140 , 141 ].…”