A Spontaneous Assembling Lipopeptide Nanoconjugate Transporting the Anthracycline Drug N-Benzyladriamycin-14-valerate for Personalized Therapy of Ewing Sarcoma.

To meet the current need for a tumor-selective, targeted therapy regimen associated with reduced toxicity, our laboratory has developed a spontaneously assembled nanostructure that resembles high-density lipoproteins (HDLs). These myristoyl-5A (MYR-5A) nanotransporters are designed to safely transport lipophilic pharmaceuticals, including a novel anthracycline drug (N-benzyladriamycin-14-valerate (AD198)). This formulation has been found to enhance the therapeutic efficacy and reduced toxicity of drugs in preclinical studies of 2D and 3D models of Ewing sarcoma (EWS) and cardiomyocytes. Our findings indicate that the MYR-5A/AD198 nanocomplex delivers its payload selectively to cancer cells via the scavenger receptor type B1 (SR-B1), thus providing a solid proof of concept for the development of an improved and highly effective, potentially personalized therapy for EWS while protecting against treatment-associated cardiotoxicity.

Lipoproteins and the Tumor Microenvironment.

The tumor microenvironment (TME) plays a key role in enhancing the growth of malignant tumors and thus contributing to "aggressive phenotypes," supporting sustained tumor growth and metastasis. The precise interplay between the numerous components of the TME that contribute to the emergence of these aggressive phenotypes is yet to be elucidated and currently under intense investigation. The purpose of this article is to identify specific role(s) for lipoproteins as part of these processes that facilitate (or oppose) malignant growth as they interact with specific components of the TME during tumor development and treatment. Because of the scarcity of literature reports regarding the interaction of lipoproteins with the components of the tumor microenvironment, we were compelled to explore topics that were only tangentially related to this topic, to ensure that we have not missed any important concepts.

Reconstituted HDL: Drug Delivery Platform for Overcoming Biological Barriers to Cancer Therapy.

Drug delivery to malignant tumors is limited by several factors, including off-target toxicities and suboptimal benefits to cancer patient. Major research efforts have been directed toward developing novel technologies involving nanoparticles (NPs) to overcome these challenges. Major obstacles, however, including, opsonization, transport across cancer cell membranes, multidrug-resistant proteins, and endosomal sequestration of the therapeutic agent continue to limit the efficiency of cancer chemotherapy. Lipoprotein-based drug delivery technology, "nature's drug delivery system," while exhibits highly desirable characteristics, it still needs substantial investment from private/government stakeholders to promote its eventual advance to the bedside. Consequently, this review focuses specifically on the synthetic (reconstituted) high-density lipoprotein rHDL NPs, evaluating their potential to overcome specific biological barriers and the challenges of translation toward clinical utilization and commercialization. This highly robust drug transport system provides site-specific, tumor-selective delivery of anti-cancer agents while reducing harmful off-target effects. Utilizing rHDL NPs for anti-cancer therapeutics and tumor imaging revolutionizes the future strategy for the management of a broad range of cancers and other diseases.