The Use of Biotinylated-Egf-Modified Gelatin Nanoparticle Carrier to Enhance Cisplatin Accumulation in Cancerous Lungs Via Inhalation
Resource
BIOMATERIALS v.30 n.20 pp.3476-3485
Journal
Biomaterials
Pages
3476-3485
Date Issued
2009
Date
2009
Author(s)
Abstract
To develop a polymer-anti cancer drug conjugate, we employed gelatin nanoparticles (GPs) as carriers of cisplatin (CDDP) with anticipated improved therapeutic effect and reduced side effects. The anticancer activities of CDDP-incorporated in GPs (GP-Pt) with biotinylated-EGF (bEGF ) modification ( GP-Pt-bEGF) were studied. GP-Pt-bEGF with EGFR affinity produced much higher Pt concentrations in A549 cells (high EGFR expression ) than in HFL1 cells (low EGFR expression). An in vitro anticancer study showed that GP-Pt-bEGF was more potent than free CDDP or GP-Pt because of its rapid effect on the cell cycle as well as a lower IC50 (1.2 mu g/ml) that inhibits A549 cell growth. PI staining showed that cells treated with GP-Pt-bEGF for only 4 h had the highest sub-G1 population. The CDDP formulations - free CDDP, GP-Pt, and GP -Pt-bEGF - were given by intratumorous injections to SCID mice in a subcutaneous model. This treatment showed that GP- Pt-bEGF had stronger anti-tumor activity and was less toxic than free CDDP in vivo. Mice treated with GP-Pt-bEGF showed slight body weight loss, whereas free CDDP treatment at the same dose caused a body weight loss of 20-30%. Furthermore, these formulations were given to mice with lung cancer via aerosol delivery. This treatment showed that inhaled GP-Pt- bEGF could target EGFR-overexpressing cells to achieve high cisplatin dosage in cancerous lungs. To summarize, gelatin nanoparticles loaded with CDDP and decorated with EGF tumor- specific ligand were successfully developed. Their in vitro and in vivo targeting ability and anticancer effect were confirmed. The aerosol delivery of the nanodrug carrier was demonstrated. Simple aerosol delivery of targeted drug carriers may prove useful for the clinical treatment of lung cancer patients.
Subjects
Gelatin nanoparticle (GPs)
Cisplatin (CDDP)
Lung cancer
Anticancer activity
Epidermal growth factor (EGF)
Inhalation
SDGs
Other Subjects
Anticancer activity; Cisplatin (CDDP); Epidermal growth factor (EGF); Gelatin nanoparticle (GPs); Inhalation; Lung cancer; Anthropometry; Atmospheric aerosols; Bioactivity; Biological organs; Cell growth; Cell membranes; Functional polymers; Growth kinetics; Nanoparticles; Peptides; Platinum compounds; Satellite navigation aids; Tumors; Platinum; antineoplastic agent; cisplatin; cisplatin plus epidermal growth factor plus gelatin nanoparticle conjugate; epidermal growth factor receptor; nanocarrier; unclassified drug; animal experiment; animal model; animal tissue; antineoplastic activity; article; biotinylation; cancer growth; cancer inhibition; cancer model; cell cycle arrest; cell cycle G1 phase; controlled study; drug conjugation; drug effect; drug formulation; drug potency; drug receptor binding; human; human cell; IC 50; in vitro study; in vivo culture; lung cancer; lung metastasis; male; mouse; nitroblue tetrazolium test; nonhuman; priority journal; receptor affinity; SCID mouse; target cell destruction; therapy effect; weight reduction; Administration, Inhalation; Animals; Antineoplastic Agents; Biocompatible Materials; Biotinylation; Cell Cycle; Cell Line, Tumor; Cisplatin; Drug Carriers; Drug Delivery Systems; Epidermal Growth Factor; Gelatin; Humans; Lung Neoplasms; Male; Materials Testing; Mice; Mice, SCID; Molecular Structure; Nanoparticles; Xenograft Model Antitumor Assays; Mus