Nanoparticles-Emerging Potential for Managing Leukemia and Lymphoma Cancers

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Abstract​

Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles (NPs) possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. In vivo, NPs enhance the therapeutic efficacy of anticancer agents when compared with conventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance. Nanomedicine has been mostly focused on solid cancers due to take advantage from the enhanced permeability and retention (EPR) effect experienced by tissues in the close vicinity of tumors, which enhance nanomedicine’s accumulation and, consequently, improve efficacy. Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are addressed differently from solid tumors. Nevertheless, NPs have provided innovative approaches to simple and non-invasive methodologies for diagnosis and treatment in liquid tumors. In this review, we consider the state of the art on different types of nanoconstructs for the management of liquid tumors, from preclinical studies to clinical trials. We also discuss the advantages of nanoplatforms for theranostics and the central role played by NPs in this combined strategy.

Keywords: nanoparticles, leukemia, lymphoma, diagnostics, therapeutics, nanotheranostics, nanomedicine

 

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Introduction​

Traditional approaches for cancer management rely on centralized diagnostic platforms that can be complex, time consuming and set for the wide spectrum of patients and malignancies (Friedman et al., 2015). These traditional approaches have been developed toward big data generation from pools of patients and for the identification of suitable biomarkers and profiles, which are the basis for standardization of chemotherapy protocols (Zaimy et al., 2017). Such strategies allowed for the development of precision oncology, in which profile data of the cancer cells enable a tailored treatment of individual patients, and have become a crucial trend for cancer management.

Nanoscale particles have been playing a central role in the detection of cancer biomarkers, which is essential for the personalized assessment at the basis of precision treatment. Versatile structural and functional properties of the nanoparticles (NPs) offer the possibility for rapid, specific, and sensitive diagnostics, toward decentralized assessment and/or ambulatory follow-up. In what therapeutics are concerned, the size range of these nanoconstructs allows them to cross biological barriers more effectively that may be further improved by functionalizing the nanoconstructs’ surface with specific ligands for precise delivery to the focus of disease (Lee et al., 2017). Moreover, NPs can work as therapeutic/imaging agents on their own or as carriers of multiple molecules that serve a specific function: tumor targeting, cancer cell ablation (via drug delivery or gene silencing), and real-time monitoring of cancer cells expansion or decay (Vinhas et al., 2015). This flexibility is crucial for theranostics, i.e., the simultaneous detection and therapy (Pedrosa et al., 2015). Most NP-based strategies have been directed at solid tumors, whereas the so-called non-solid tumors, such as lymphoma and leukemia, have not mobilized that much attention.

Conventional chemotherapy in hematological cancers is challenged by the poor selectivity, resulting in low therapeutic efficacy and pronounced adverse side effects. These issues may be overturned by innovative nanomedicine approaches. In this review, we shall focus on nanotechnology advances that support leukemia and lymphoma biomarker detection and targeted treatment. Hematological disorders are very good candidates for such targeting since the molecular basis of each subgroup of patients is very well defined by common chromosomal translocations, shared mutations in oncogenes, gene expression profiles, and immune phenotype. Moreover, a simple blood sample (liquid biopsy) provides access to the patient’s full tumor profile, giving insightful information to support more focused therapeutic regimens—Figure 1. Unlike solid tumors that require NPs to reach the site of action, liquid tumors are spread throughout the bloodstream. Most of the barriers that NPs face to reach solid tumors are not critical in liquid tumors since circulating tumor cells are freely exposed to these agents. However, while in circulation, NPs may still be opsonized by blood proteins followed by recognition by the mononuclear phagocyte system (Sriraman et al., 2014). As such, liquid tumors require slightly different diagnostic treatment and targeting strategies that shall be herein discussed.