Naturally Equipped Urinary Exosomes Coated Poly (2−ethyl−2−oxazoline)−Poly (D, L−lactide) Nanocarriers for the Pre−Clinical Translation of Breast Cancer

Abstract

Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this work, urinary exosomes (UEs) with high expression of CD9 and CD47 were extracted from breast cancer patients by a non−invasive method. Here, a nanotechnology approach is reported for tumor homologous targeting via CD9 and phagocytosis escape via CD47 through UE−coated poly (2−ethyl−2−oxazoline)−poly (D, L−lactide) (PEOz−PLA) nanoparticles (UEPP NPs). The cytotoxic agent doxorubicin (DOX)−loaded UEPP (UEPP−D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment. In vitro experiments revealed that UEPP−D NPs exhibited significantly improved cellular uptake, cytotoxicity, and apoptosis in MCF−7 cell lines as compared to DOX−loaded PEOz−PLA nanoparticles (PP−D NPs) and free DOX. More importantly, anti−phagocytosis and pharmacokinetic studies confirmed that UEPP−D NPs had superior immune escape ability and significantly prolonged the drug’s bloodstream circulation in vivo. Finally, UEPP−D NPs showed a markedly higher antitumor efficacy and lower side−toxicity in MCF−7 tumor bearing nude mice model. Thus, this versatile nano−system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment.

Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer

“…Thus, urinary EVs isolates were able to detect disease-specific molecules undetectable in urine, either because of their low concentration in the bulk fluid or because of their location on EVs [ 21 ]. In fact, EVs could serve as a more specific source for biomarker discovery than unfractionated urine, and provide precision diagnostic information without invasive [ 22 , 23 ]. Previous studies have shown that the biomolecules change at EVs level occurs earlier than that in body fluids [ 24 ].…”

Artificial and Naturally Derived Phospholipidic Bilayers as Smart Coatings of Solid-State Nanoparticles: Current Works and Perspectives in Cancer Therapy

“…Again, doxorubicin was exploited to prove the efficacy of a system aimed at tumor drug delivery for EV-coated polymeric NPs. In this case, as already cited in Section 2.2 for the in vitro tests, the in vivo experiments showed an increased tumor accumulation and tumor growth inhibition in mice, proving the efficacy of the therapy [ 76 ].…”

“…In this work, the idea was to exploit a body fluid that can be picked up by the patient without invasive processes to obtain tumor-targeting exosomes. In vitro results showed an enhanced rate of apoptosis when employing these nanoconstructs, which was attributed to the increased targeting ability of cancer patient-derived exosomes [ 76 ].…”

Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management

“…While loading DOX in SEVs reduces its cardiotoxicity [ 562 , 563 ], it also enhances its efficacy when compared to traditional administration [ 562 , 564 ]. Packaging DOX into SEVs increases its stability, thus allowing a better collection within the tumor [ 564 ] with more limited side toxicity [ 565 ]. It holds the same for PTX, SEVs being more efficient than free PTX and liposomal PTX in inhibiting cancer cell growth [ 566 ].…”