Aim: To demonstrate that exosomes (exo) could increase the therapeutic index of doxorubicin (DOX). Materials & methods: Exosomes were characterized by nanoparticle tracking analysis and western blot. Tissue toxicity was evaluated by histopathological analysis and drug efficacy by measuring tumor volume. DOX biodistribution was analyzed by MS. Results: Exosomal doxorubicin (exoDOX) avoids heart toxicity by partially limiting the crossing of DOX through the myocardial endothelial cells. For this reason, mice can be treated with higher concentration of exoDOX thus increasing the efficacy of DOX as demonstrated in breast and ovarian mouse tumors. Conclusion: ExoDOX is safer and more effective than free DOX. Importantly, the first spontaneous transformed syngeneic model of high-grade serous ovarian cancer was utilized for providing a new therapeutic opportunity.
Inorganic nanoparticles (NPs) including those derived from metals (e.g., gold, silver), semiconductors (e.g., quantum dots), carbon dots, carbon nanotubes, or oxides (e.g., iron oxide), have been deeply investigated recently for diagnostic and therapeutic purposes in oncology. Compared to organic nanomaterials, inorganic NPs have advanced advantages and unique characteristics for better imaging and drug delivery. Still, only a limited number of inorganic NPs are translated into clinical practice. In this review, we discuss the progression of inorganic NPs for cancer therapy and imaging, focusing our attention on opportunities, limitations and challenges for the main constituting nanomaterials, including metallic and magnetic NPs. In particular, the pre-clinical and clinical trials from the bench toward clinic are here investigated.
The application of nanotechnology in the medical field is called nanomedicine. Nowadays, this new branch of science is a point of interest for many investigators due to the important advances in which we assisted in the lasts decades, in particular for cancer treatment. Cancer nanomedicine has been applied in different fields such as drug delivery, nanoformulation and nanoanalytical contrast reagents. The application of nanotechnology to pharmaceutical science allowed to build up nanosystems based on at least two stage vectors (drug/nanomaterial), which often shown a better pharmacokinetics (PK), bioavailability and biodistribution. As result of these advantages, the nanomaterials accumulate passively in the tumor (enhanced permeability and retention, EPR) decreasing side effects of free drug. In the last decades, many new drug formulations have been translated from the bench to the bedside. In this review, we describe the main drug nanoformulations based on different types of organic nanoparticles (NPs), the advantages that the new formulations have over to their free drug counterparts and how nanodrugs have improved the clinical care.
Aim: To test the efficacy and toxicity of exosomal doxorubicin (exoDOX) compared with free doxorubicin. Materials & methods: The cytotoxic effects of exoDOX were tested in vitro and in nude mice by measuring the tumor volume. The toxic effects were evaluated by measuring the bodyweight and through histopathologic analyses. The biodistribution of DOX was assessed by MS. Results: In vitro and in vivo studies showed that exosomes did not decrease the efficacy of DOX. Surprisingly, exoDOX showed no cardiotoxicity as observed in DOX-treated mice and MS studies confirmed that the accumulation of exoDOX in the heart was reduced by approximately 40%. Conclusion: We demonstrated that exoDOX was less toxic than DOX through its altered biodistribution.
DNA origami systems could be important candidates for clinical applications. Unfortunately, their intrinsic properties such as the activation of non-specific immune system responses leading to inflammation, instability in physiological solutions, and a short in vivo lifetime are the major challenges for real world applications. A compact short tube DNA origami (STDO) of 30 nm in length and 10 nm in width was designed to fit inside the core of a stealth liposome (LSTDO) of about 150 nm to remote load doxorubicin. Biocompatibility was tested in three-dimensional (3D) organoid cultures and in vivo. Efficacy was evaluated in different cell lines and in a xenograft breast cancer mouse model. As described in a previous work, LSTDO is highly stable and biocompatible, escaping the recognition of the immune system. Here we show that LSTDO have an increased toleration in mouse liver organoids used as an ex vivo model that recapitulate the tissue of origin. This innovative drug delivery system (DDS) improves the antitumoral efficacy and biodistribution of doxorubicin in tumor-bearing mice and decreases bone marrow toxicity. Our application is an attractive system for the remote loading of other drugs able to interact with DNA for the preparation of liposomal formulations.