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Lipid-coated Cisplatin nanoparticles induce neighboring effect and exhibit enhanced anticancer efficacy.
- Source :
-
ACS nano [ACS Nano] 2013 Nov 26; Vol. 7 (11), pp. 9896-904. Date of Electronic Publication: 2013 Oct 03. - Publication Year :
- 2013
-
Abstract
- Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading and encapsulation efficiency has been difficult due to the poor solubility of CDDP. However, this barrier has been overcome with a reverse microemulsion method appropriating CDDP's poor solubility to our advantage promoting the synthesis of a pure cisplatin nanoparticle with a high drug loading capacity (approximately 80.8 wt %). Actively targeted CDDP NPs exhibited significant accumulation in human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent antitumor efficacy through the neighboring effect at a dose of 1 mg/kg when injected weekly via iv without inducing nephrotoxicity. The neighboring effect regards an observation made in vivo when the tumor cells that took up CDDP NPs released active drug following apoptosis. Via diffusion, surrounding cells that were previously unaffected showed intake of the released drug and their apoptosis soon followed. This observation was also made in vitro when A375M melanoma tumor cells incubated with CDDP NPs exhibited release of active drug and induced apoptosis on untreated neighboring cells. However, the neighboring effect was unique to rapidly proliferating tumor cells. Liver functional parameters and H&E staining of liver tissue in vivo failed to detect any difference between CDDP NP treated and control groups in terms of tissue health. By simultaneously promoting an increase in cytotoxicity and a lesser degree of side effects over free CDDP, CDDP NPs show great therapeutic potential with lower doses of drug while enhancing anticancer effectiveness.
- Subjects :
- Animals
Apoptosis
Cell Line, Tumor
Diffusion
Drug Carriers chemistry
Female
Green Fluorescent Proteins metabolism
Humans
Inhibitory Concentration 50
Liver pathology
Mice
Mice, Nude
Nanomedicine methods
Neoplasm Transplantation
Neoplasms, Experimental drug therapy
Solubility
Antineoplastic Agents administration & dosage
Cisplatin administration & dosage
Coated Materials, Biocompatible chemistry
Lipids chemistry
Nanoparticles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1936-086X
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- ACS nano
- Publication Type :
- Academic Journal
- Accession number :
- 24083505
- Full Text :
- https://doi.org/10.1021/nn403606m