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Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo.

ABSTRACT: The cell surface glycoprotein CD44 is expressed in cancer cells and has been used as a therapeutic target in preclinical studies. However, the ubiquitous expression of CD44 in numerous cell types, including hematopoietic cells, has hindered its application in targeted therapy. Here, we demonstrated that CD44 was activated on breast cancer cells but was inactive on normal cells in vitro and in vivo. We analyzed 34 clinical primary tumor and normal breast tissues and demonstrated that CD44 was in an active state on breast cancer cells but in an inactive state on normal cells. Furthermore, based on the binding property of CD44 with its ligand hyaluronan (HA), we self-assembled HA-coated nanoparticles and studied their selective targeting efficacy. Our results indicate that HA-coated nanoparticles bearing the CD44 ligand selectively targeted cancer cells both in vitro and in vivo, killing breast cancer cells while sparing normal cells. Our study suggested that the active state of CD44 plays a crucial role in the selective targeting of breast cancer cells by avoiding nonspecific toxicity to CD44-quiescent normal cells. These findings may provide a new idea for the selective targeting of cancer cells in other human cancers.

SUBMITTER: Yang C

PROVIDER: S-EPMC4558151 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo.

Yang Cuixia C He Yiqing Y Zhang Huizhen H Liu Yiwen Y Wang Wenjuan W Du Yan Y Gao Feng F

Oncotarget 20150601 17

The cell surface glycoprotein CD44 is expressed in cancer cells and has been used as a therapeutic target in preclinical studies. However, the ubiquitous expression of CD44 in numerous cell types, including hematopoietic cells, has hindered its application in targeted therapy. Here, we demonstrated that CD44 was activated on breast cancer cells but was inactive on normal cells in vitro and in vivo. We analyzed 34 clinical primary tumor and normal breast tissues and demonstrated that CD44 was in ...[more]

PMID: 25909172

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Project description:This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU). Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. The drug encapsulation and loading were determined by the indirect method using HPLC. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 ± 5.8%, and drug loading capacity of 5.2 ± 1.2%. NMR spectra confirmed the coating of AMSN with the CMC layer. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. AMSN-CMC-FU gel and AMSN-FU gel were "minimally irritating" to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.

Dataset Information

Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo.

Publications

Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo.

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