Lipid Droplets in Cancer: From Composition and Role to Imaging and Therapeutics

Abstract

Cancer is the second most common cause of death worldwide, having its origin in the abnormal growth of cells. Available chemotherapeutics still present major drawbacks, usually associated with high toxicity and poor distribution, with only a small fraction of drugs reaching the tumour sites. Thus, it is urgent to develop novel therapeutic strategies. Cancer cells can reprogram their lipid metabolism to sustain uncontrolled proliferation, and, therefore, accumulate a higher amount of lipid droplets (LDs). LDs are cytoplasmic organelles that store neutral lipids and are hypothesized to sequester anti-cancer drugs, leading to reduced efficacy. Thus, the increased biogenesis of LDs in neoplastic conditions makes them suitable targets for anticancer therapy and for the development of new dyes for cancer cells imaging. In recent years, cancer nanotherapeutics offered some exciting possibilities, including improvement tumour detection and eradication. In this review we summarize LDs biogenesis, structure and composition, and highlight their role in cancer theranostics.

Lung Adenocarcinoma Cell Sensitivity to Chemotherapies: A Spotlight on Lipid Droplets and SREBF1 Gene

“…In general, the mechanisms underlying LD biogenesis and formation remain not well understood. One cannot exclude that LD’s size, composition, and localization rather than the LD area will determine their role in anticancer drug resistance [ 48 ].…”

Cellular communication through extracellular vesicles and lipid droplets

“…Of these, the greatest overlap (96.84%) was observed in the LD proteome of cells infected with Hepatitis C virus (HCV) (Rösch et al, 2016) compared to EVs isolated from human metastatic melanoma (Crescitelli et al, 2020) (Table 2). We found this particularly interesting for two reasons: firstly, LDs are commonly increased in cancerous cells, and accumulate during virus infection (Antunes et al, 2022;Monson, Crosse, et al, 2021;Monson, Trenerry, et al, 2021). This high abundance of LDs in tissue samples increase the difficultly of successful isolation of pure EVs particularly in small, low density • Involved in Exosome biogenesis (Baietti et al, 2012) • Used as exosome marker (Duijvesz et al, 2013) LD: (human (Bersuker & Olzmann, 2017), mouse (Bosch et al, 2020;Wang et al, 2015) • unknown AnxA* EV: (mouse, human, rat)…”

A Glimpse into Dendrimers Integration in Cancer Imaging and Theranostics

“…Thus, LDs can be viewed as future cancer hallmarks. Intracellular targeting of lipid droplets is also now becoming an imaging tool to monitor cancer cells and the targets of innovative therapeutic approaches [ 112 ]. Using “click” chemistry, multivalent niacin–polymeric (including dendrimer) conjugates were shown to target LDs [ 113 ].…”

“…Using “click” chemistry, multivalent niacin–polymeric (including dendrimer) conjugates were shown to target LDs [ 113 ]. The production of nitric oxide (NO) following treatment was significantly increased and a reduction in a LD relevant enzyme (diacylglycerol acyltransferase, DGAT2) involved in triglyceride biosynthesis was observed [ 112 ]. This strategy can be applied in the future for the treatment of cancer and other diseases that involve the accumulation of triglycerides/LDs.…”