Intracellular and extracellular targets as mechanisms of cancer therapy by nanomaterials in relation to their physicochemical properties.

Charlene Andraos,Mary Gulumian

doi:10.1002/wnan.1680

Abstract

Cancer nanomedicine has evolved in recent years and is only expected to increase due to the ease with which nanomaterials (NMs) may be manipulated to the advantage of the cancer patient. The success of nanomedicine is dependent on the cell death mechanism, which in turn is dependent on the organelle initially targeted. The success of cancer nanomedicine is also dependent on other cellular mechanisms such as the induction of autophagy dysfunction, manipulation of the tumor microenvironment (TME) and secretome or induction of host immune responses. Current cancer phototherapies for example, photothermal‐ or photodynamic therapies as well as radio enhancement also form a major part of cancer nanomedicine. In general, cancer nanomedicine may be grouped into those NMs exhibiting inherent anti‐cancer properties that is, self‐therapeutic NMs (Group 1), NMs leading to localization of phototherapies or radio‐enhancement (Group 2), and NMs as nanocarriers in the absence or presence of external radiation (Group 3). The recent advances of these three groups, together with their advantages and disadvantages as well as their cellular mechanisms and ultimate outcomes are summarized in this review. By exploiting these different intracellular mechanisms involved in initiating cell death pathways, it is possible to synthesize NMs that may have the desirable characteristics to maximize their efficacy in cancer therapy. Therefore, a summary of these important physicochemical characteristics is also presented that need to be considered for optimal cancer cell targeting and initiation of mechanisms that will lead to cancerous cell death.This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseToxicology and Regulatory Issues in Nanomedicine > Toxicology of NanomaterialsToxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

Highlights

The advances in nanomedicine have gained much attention in the last two decades based on the benefits of nanomaterials (NMs) over those of traditional chemotherapeutics
Once at the tumor site, the NM may initiate cell killing through the assistance of an externally applied radiation source that results in heat production, reactive oxygen species (ROS) production, or radio enhancement
Moosavi et al (2016) showed that nitrogendoped TiO2 NPs enhanced PDT in K562 leukemia cells through ROS generation and autophagy induction during which LC3 was cleaved by autophagy-related protein 4 (Atg4) and subsequently conjugated to phosphatidylethanolamine (LC3-II) by Atg3, which allowed LC3-II to insert into autophagosomes membranes

Summary

Introduction

The advances in nanomedicine have gained much attention in the last two decades based on the benefits of nanomaterials (NMs) over those of traditional chemotherapeutics. Gao et al (2014) could demonstrate the successful induction of LMP and apoptosis via ROS generation by Au-zinc oxide (ZnO) nanohybrids, targeted to the lysosomes of human liver HepG2 cancer cells.

Results

Conclusion