Nanomedicine Tumor Targeting

Nanomedicines are extensively explored for cancer therapy. By delivering drug molecules more efficiently to pathological sites and by attenuating their accumulation in healthy organs and tissues, nanomedicine formulations aim to improve the balance between drug efficacy and toxicity. More than 20 cancer nanomedicines are approved for clinical use, and hundreds of formulations are in (pre)clinical development. Over the years, several key pitfalls have been identified as bottlenecks in nanomedicine tumor targeting and translation. These go beyond materials- and production-related issues, and particularly also encompass biological barriers and pathophysiological heterogeneity. In this manuscript, the author describes the most important principles, progress, and products in nanomedicine tumor targeting, delineates key current problems and challenges, and discusses the most promising future prospects to create clinical impact.

Introduction

Cancer therapy relies on (combinations of) surgery, radiotherapy, chemotherapy, molecularly targeted therapy, hormone therapy, and immunotherapy. The choice of treatment depends on tumor type, location, and stage, as well as on the general well-being of the patient. Complete tumor removal is the ultimate goal of therapeutic intervention and can – in case of early-stage disease – typically be achieved using surgery. In advanced stages, however, cancers invade healthy tissue and metastasize to distant sites, thereby compromising the success of surgery and calling for combination regimens involving systemic drug therapy.

Anticancer drug therapy is often only moderately effective. This is because the majority of drugs do not accumulate well in tumors and metastases. Moreover, anticancer drug treatment typically comes with severe side effects, as the agents have a large volume of distribution and therefore localize in healthy organs and tissues. It is important to note that this situation does not only apply to classical chemotherapeutics, but also to molecularly targeted drugs, like kinase inhibitors, which also present with suboptimal biodistribution and tumor targeting profiles, and which therefore also often show suboptimal therapeutic efficacy and significant off-target toxicity.

To improve the therapeutic index of anticancer drugs, many different drug delivery systems have been designed and evaluated over the years.[1-3] These include liposomes, polymers, proteins, and micelles, as well as nature-derived and inorganic nanomaterials (Figure 1). Besides such synthetic nanomedicine formulations, which often times originate from chemical engineering, materials science, and pharmaceutical technology laboratories, also biotechnologically produced delivery systems are evaluated for tumor targeting, represented most prominently by antibody-drug conjugates. The former are mostly used for standard chemotherapeutic drugs, like doxorubicin and paclitaxel, while the latter are traditionally employed for highly potent toxins, such as auristatin and emtansine.[4, 5] The former have furthermore been attracting a lot of attention for nucleic acid delivery, as exemplified by the successful clinical development of lipid nanoparticles for siRNA targeting hepatocytes and mRNA-based vaccination strategies.[6, 7]

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Twan Lammers, Nanomedicine Tumor Targeting, First published: 15 February 2024 https://doi.org/10.1002/adma.202312169