Exploiting Nanomaterial‐Mediated Autophagy for Cancer Therapy

Abstract

Autophagy is a conserved process that is critical for sequestering and degrading proteins, damaged or aged organelles, and for maintaining cellular homeostasis under stress conditions. Despite its dichotomous role in health and diseases, autophagy usually promotes growth and progression of advanced cancers. In this context, clinical trials using chloroquine and hydroxychloroquine as autophagy inhibitors have suggested that autophagy inhibition is a promising approach for treating advanced malignancies and/or overcoming drug resistance of small molecule therapeutics (i.e., chemotherapy and molecularly targeted therapy). Efficient delivery of autophagy inhibitors may further enhance the therapeutic effect, reduce systemic toxicity, and prevent drug resistance. As such, nanocarrier‐based drug delivery systems have several distinct advantages over free autophagy inhibitors that include increased circulation of the drugs, reduced off‐target systemic toxicity, increased drug delivery efficiency, and increased solubility and stability of the encapsulated drugs. With their versatile drug encapsulation and surface‐functionalization capabilities, nanocarriers can be engineered to deliver autophagy inhibitors to tumor sites in a context‐specific and/or tissue‐specific manner. This review focuses on the role of nanomaterials utilizing autophagy inhibitors for cancer therapy, with a focus on their applications in different cancer types.

Selective Autophagy Pathway of Nanoparticles and Nanodrugs: Drug Delivery and Pathophysiological Effects

“…Notably, many of the aforementioned nanoparticles or nanodrugs elicit autophagic response in cancer cells, elucidating the possibility of exploiting nanoparticles or nanodrugs for cancer therapy. [153,[249][250][251] Several nanoparticles such as copper, [120] gold, [165] silver, [132] silica, [127,166] polymeric materials, [105][106][107]111] were used to induced autophagy for cancer therapy. Besides, nanoparticles or nanodrugs that have a therapeutic effect directly or in combination with various drug molecules and antibodies have been employed for the modulating autophagy for cancer therapy.…”

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems

“…Despite the usefulness of utilizing more common carriers included liposomes, micelles, and polymeric nanoparticles for autophagy medication (Figure 3), some researchers suggest that employing metal nanoparticles like silver, gold, and iron oxide either alone, in combination with autophagy drug suppressors or with an external inducer (like laser exposure) can result in excessive autophagy inhibition. Moreover, a few studies focused on other nanomaterials like nanogels, molybdenum disulfide (2D nanosheets), and lipid calcium phosphate nanoparticles on cancer therapy [34].…”

“…Additionally, non-targeted delivery is another pitfall associated with autophagy modulators. On the other hand, nanocarriers have demonstrated great potential in delivery of autophagy modulators [34]. To date, several nanocarriers such as liposomes [35,36], niosomes [37], micelles [38,39], carbon dots (CDs) [40] and polymeric ones [41,42] have been applied for delivery of drugs.…”

Targeting autophagy in thyroid cancers

“…In contrast, miR-30d negatively regulated cisplatin-activated autophagic response by downregulating BECN1, as a result, sensitizing ATC cells to cisplatin treatment both in vitro and in vivo . Considering these promising yet controversial results, we would like to advocate the use of comprehensive detection and intervention methods when examining the role of autophagy in mediating the treatment outcome of small-molecular therapeutics in thyroid cancers (Wei et al 2018a).…”