Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery

[摘要] Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44+/CD24−/lowhuman breast cancer cells (BT-474EMT).CMHA stabilized particles (nCaPCMHA) were loaded with the chemotherapy drugcis-diamminedichloroplatinum(II) (CDDP) to form nCaPCMHACDDP.nCaPCMHACDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a −43 mV zeta potential.nCaPCMHACDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days.Surface plasmon resonance showed that nCaPCMHACDDP binds to CD44, but less effectively than CMHA or hyaluronan.nCaPCMHA-AF488was taken up by CD44+/CD24−BT-474EMTbreast cancer cells within 18 hours.nCaPCMHACDDP was as cytotoxic as free CDDP against the BT-474EMTcells. Subcutaneous BT-474EMTtumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaPCMHACDDP.This was likely due to a lack of distribution of nCaPCMHACDDP throughout the dense tumor tissue that limited drug diffusion.

[学科分类] 分子生物学，细胞生物学和基因