Delivery of chemotherapeutic drugs in tumour cell-derived microparticles

Abstract

Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

“…Previously, we have shown that drug-packaging MPs can enter and induce tumor cell apoptosis. 15 Here, we also found that Cis-MPs were cytotoxic to H22, CT26 and Lewis lung cancer cells (Fig. 5B), which, however, was enhanced by LDI (Fig.…”

“…After 18-20 h, supernatants were used for MPs isolation as described previously. 15 Briefly, supernatants were centrifuged at 1,300 rpm for 10 min to remove whole cells and then centrifuged at 5,000 rpm for 10 min and 14,000 g for 2 min to remove debris. The supernatants were further centrifuged at 14,000 g for 60 min to pellet MPs.…”

“…14 Such specialized subcellular vesicles with 0.1-1 mm sizes are called microparticles (MPs). Recently, we have demonstrated that tumor cell-derived MPs (T-MPs) are capable of delivering chemotherapeutic drugs or oncolytic adenoviruses to nuclei of TRCs and disrupting them through a lysosomemediated pathway, [15][16][17][18][19] suggesting that drug-packaging MPs might be a potential means to improve antitumor immunity by abrogating TRCs. However, whether such drug-packaging MP-based approach of targeting TRCs can be strengthened by other means is not clear.…”

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

“…Recent studies have highlighted that after treatment with chemotherapeutic drugs, apoptotic tumor cells can release microparticles, which may contain DAMPs that stimulate DCs and can be used to effectively kill tumor cells. 33,34 Therefore, when appropriate antigenic transfer to DCs occurs, the acute release of DAMPs may help to elicit immune responses in cancer-bearing patients. Maturation and activation of DCs is required for DC migration to T-cell regions within the lymph node.…”

Switch of glycolysis to gluconeogenesis by dexamethasone for treatment of hepatocarcinoma

“…However, the administration of Dex may induce stomach and duodenum ulceration in hepatocarcinoma patients 54 . Recently, we demonstrated that tumour cell-derived micro- * * * * particles can deliver drugs to tumour cells in vivo without side effect 55 . This new delivery technology may be helpful in overcoming the limitations of Dex in hepatocarcinoma patients.…”