Targeting tumor metastases: Drug delivery mechanisms and technologies

Abstract

Primary sites of tumor are the focal triggers of cancers, yet it is the subsequent metastasis events that cause the majority of the morbidity and mortality. Metastatic tumor cells exhibit a phenotype that differs from that of the parent cells, as they represent a resistant, invasive subpopulation of the original tumor, may have acquired additional genetic or epigenetic alterations under exposure to prior chemotherapeutic or radiotherapeutic treatments, and reside in a microenvironment differing from that of its origin. This combination of resistant phenotype and distal location make tracking and treating metastases particularly challenging. In this review, we highlight some of the unique biological traits of metastasis, which in turn, inspire emerging strategies for targeted imaging of metastasized tumors and metastasis-directed delivery of therapeutics.

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors

“…It is important to mention that AuNP-PEG-FA are subject to passive targeting through the EPR effect and active targeting do to the presence of the folic acid receptor in tumor cells. The poor degree of initial accumulation in the lung tumors may be because early-stage tumor metastases are usually poorly vascularized which reduces accumulation due to the EPR effect [62]. This would also explain why the accumulation of B16-EVs in tumors (0.8% of injected dose) is lower than what is usually observed in xenograft models that generate well-vascularized tumors.…”

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy – an illustration with firsthand examples

“…However, the EPR effect may not occur in metastatic tumors, especially when they are at an early stage and present as micron-sized lesions [86,87] . Moreover, owing to the highly selective biological barriers presented in Figure 1, including the predominant hepatic removal of foreign particles and the blood brain barrier (BBB), off-target accumulation of NPs in unintended organs occurs frequently [88] . Therefore, it is challenging to transport NPs to metastatic tumors by simple passive and/or active targeting approaches.…”

From Composition to Cure: A Systems Engineering Approach to Anticancer Drug Carriers

“…Active targeting may permit the identification of and homing to sites of systemic disease, provided the metastatic niche has a targetable feature. [41] …”