Journal
ACS NANO
Volume 6, Issue 2, Pages 1795-1805Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn2048526
Keywords
dual-targeted nanomedicine; PSMA; anti-PSMA; magnetic targeting; prostate cancer therapy
Categories
Funding
- National Science Council of the Republic of China
- Chang Gung Memorial Hospital
- Industrial Technology Research Institute [NSC 100-2221-E-182-005, NSC 99-2221-E-182-068, NSC 98-2221-E-182-045-MY3, CMRPD140041, CMRPD140061, CMRPG391781, CMRPG-391782, NMRPD1A1271, AF51RQ3000]
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A key issue in cancer therapy Is how to enhance the tumor-targeting efficacy of chemotherapeutic agents. In this study, we developed a cooperative dual-targeted delivery platform for paclitaxel (PTX) that has potential application as a powerful prostate cancer treatment. The nanomedicine was prepared by first conjugating PTX to nontoxic high-magnetization nanocarriers which can be actively guided and targeted by an external magnet. Next, the surface was functionalized with carboxylated o-(2-aminoethyl)polyethyleneglycol (NH2-EPEG-COOH) to enable uptake by the reticuloendothelial system. Antiprostate-specific membrane antigen antibodies (APSMAs) were then conjugated onto the carrier to recognize the extracellular domain of the prostate-cancer specific membrane antigen (MA), thus binding to cancer cells as a secondary active targeting mechanism. We found a significant enhancement of PTX concentration at the tumor site by nearly 20-fold. In addition, the drug half-life was prolonged more than 4.1-fold (from 24 to 99 h) at 37 degrees C. Low-dose (4.5 mg/kg) injection of the dual-targeted therapeutic nanomedicine in the presence of magnetic targeting significantly prolonged the median survival of nude mice from 35 to 58 days compared to mice that received a high dose (6 mg/kg) of free PTX. This report demonstrates the potential utility of targeted nanomedicine in the clinical treatment of cancer.
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