TY - JOUR
T1 - Delivery of cytotoxic drugs from carrier cells to tumour cells by apoptosis
AU - Ma, J.
AU - Gallo, J. M.
N1 - Funding Information:
Supported in part by grant CA 06927 from the NIH. Thanks to Jonathan Boyd for confocal microscopy.
PY - 1998
Y1 - 1998
N2 - A new drug delivery approach, apoptotic-induced drug delivery (AIDD), is presented that is based on apoptosis as a mechanism to trigger delivery of drugs from carrier cells. It was investigated whether apoptotic drug-loaded carrier cells could deliver drugs to tumour cells by various mechanisms, including drug release through a more permeable apoptotic cell membrane, and by phagocytosis of drug-loaded apoptotic cells by tumour cells. The feasibility of this novel concept was evaluated in an in vitro carrier cell model that consisted of S49 mouse lymphoma cells that apoptose upon exposure to dexamethasone (DX). Membrane permeability was evaluated by measurement of release of a fluorescent dye (calcein-AM, C-AM) from C-AM-loaded S49 cells. Phagocytotsis of fluorescent PKH-26-labeled S49 cells was determined in co-culture studies with rat glioma (RG-2) cells using fluorescence microscopy and flow cytometry. Cytotoxicity of RG-2 cells due to temozolomide (TMZ)-loaded S49 cells was evaluated by a colony formation assay following co-culture of these cells for up to 8 h. Calcein release from S49 cells was enhanced by approximately 30% at 48 h following treatment with DX compared to control S49 cells. Based on both flow cytometric and microscopic analyses, RG2 phagocytized apoptotic S49 cells to a four- to sevenfold greater extent than control S49 cells at co-incubation times from 4-48 h. The TMZ-loaded apoptotic S49 cells caused the largest degree of toxicity, about 50% cell kill, whereas TMZ-loaded control S49 caused 30% cell kill. The preliminary data suggest that AIDD should be further explored.
AB - A new drug delivery approach, apoptotic-induced drug delivery (AIDD), is presented that is based on apoptosis as a mechanism to trigger delivery of drugs from carrier cells. It was investigated whether apoptotic drug-loaded carrier cells could deliver drugs to tumour cells by various mechanisms, including drug release through a more permeable apoptotic cell membrane, and by phagocytosis of drug-loaded apoptotic cells by tumour cells. The feasibility of this novel concept was evaluated in an in vitro carrier cell model that consisted of S49 mouse lymphoma cells that apoptose upon exposure to dexamethasone (DX). Membrane permeability was evaluated by measurement of release of a fluorescent dye (calcein-AM, C-AM) from C-AM-loaded S49 cells. Phagocytotsis of fluorescent PKH-26-labeled S49 cells was determined in co-culture studies with rat glioma (RG-2) cells using fluorescence microscopy and flow cytometry. Cytotoxicity of RG-2 cells due to temozolomide (TMZ)-loaded S49 cells was evaluated by a colony formation assay following co-culture of these cells for up to 8 h. Calcein release from S49 cells was enhanced by approximately 30% at 48 h following treatment with DX compared to control S49 cells. Based on both flow cytometric and microscopic analyses, RG2 phagocytized apoptotic S49 cells to a four- to sevenfold greater extent than control S49 cells at co-incubation times from 4-48 h. The TMZ-loaded apoptotic S49 cells caused the largest degree of toxicity, about 50% cell kill, whereas TMZ-loaded control S49 caused 30% cell kill. The preliminary data suggest that AIDD should be further explored.
KW - Apoptosis
KW - Drug delivery
KW - Membrane permeability
KW - Phagocytosis
UR - http://www.scopus.com/inward/record.url?scp=0006186870&partnerID=8YFLogxK
U2 - 10.1023/A:1009603023214
DO - 10.1023/A:1009603023214
M3 - Article
AN - SCOPUS:0006186870
SN - 1360-8185
VL - 3
SP - 195
EP - 202
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
IS - 3
ER -