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Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.

Woodman JL, Suh MS, Zhang J, Kondaveeti Y, Burgess DJ, White BA, Prestwich GD, Kuhn LT - Int J Cell Biol (2015)

Bottom Line: CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days.Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP.This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA ; Department of Reconstructive Sciences, UConn Health, Farmington, CT 06030, USA.

ABSTRACT
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(-/low) human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaP(CMHA)CDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaP(CMHA-AF488) was taken up by CD44(+)/CD24(-) BT-474EMT breast cancer cells within 18 hours. nCaP(CMHA)CDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP. This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

No MeSH data available.


Related in: MedlinePlus

Cytotoxicity examination of CMHA, nCaPCMHA, CDDP, Aq CDDP, Aq CDDP-CMHA and nCaPCMHACDDP evaluated against BT-474 and BT-474EMT cells using an MTS assay. (a) Evaluation of CMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (b) Evaluation of nCaPCMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (c) Cytotoxicity evaluation using BT-474 (CD44−) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted. (d) Cytotoxicity evaluation using BT-474EMT (CD44+) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted.
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fig7: Cytotoxicity examination of CMHA, nCaPCMHA, CDDP, Aq CDDP, Aq CDDP-CMHA and nCaPCMHACDDP evaluated against BT-474 and BT-474EMT cells using an MTS assay. (a) Evaluation of CMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (b) Evaluation of nCaPCMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (c) Cytotoxicity evaluation using BT-474 (CD44−) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted. (d) Cytotoxicity evaluation using BT-474EMT (CD44+) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted.

Mentions: The cytotoxicity of CMHA, nCaPCMHA, CDDP, Aq CDDP, Aq CDDP-CMHA, and nCaPCMHACDDP was examined against BT-474 (CD44 negative) and BT-474EMT (CD44 positive) cells. These studies confirmed that CMHA did not have any inherent toxicity to either cell type (Figure 7(a)). The CMHA stabilized nCaPCMHA also had no cytotoxicity when tested at the concentrations which matched the amount of nCaP in the nCaPCMHACDDP test groups (Figure 7(b)). The IC50 curves of CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP against BT-474 cells are shown in Figure 7(c). The IC50 curves of CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP against BT-474EMT cells are shown in Figure 7(d). The IC50 values calculated from these curve fits are shown in Table 2. nCaPCMHACDDP and Aq CDDP were significantly more cytotoxic than CDDP alone against BT-474 cells and Aq CDDP-CMHA was significantly less cytotoxic (P ≤ 0.001). nCaPCMHACDDP had comparable cytotoxicity to CDDP against BT-474EMT cells. Aq CDDP-CMHA was significantly less cytotoxic than CDDP (P ≤ 0.001) and Aq CDDP was significantly more cytotoxic (P ≤ 0.05) for BT-474EMT cells.


Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.

Woodman JL, Suh MS, Zhang J, Kondaveeti Y, Burgess DJ, White BA, Prestwich GD, Kuhn LT - Int J Cell Biol (2015)

Cytotoxicity examination of CMHA, nCaPCMHA, CDDP, Aq CDDP, Aq CDDP-CMHA and nCaPCMHACDDP evaluated against BT-474 and BT-474EMT cells using an MTS assay. (a) Evaluation of CMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (b) Evaluation of nCaPCMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (c) Cytotoxicity evaluation using BT-474 (CD44−) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted. (d) Cytotoxicity evaluation using BT-474EMT (CD44+) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig7: Cytotoxicity examination of CMHA, nCaPCMHA, CDDP, Aq CDDP, Aq CDDP-CMHA and nCaPCMHACDDP evaluated against BT-474 and BT-474EMT cells using an MTS assay. (a) Evaluation of CMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (b) Evaluation of nCaPCMHA alone against BT-474 and BT-474EMT cells, showing no cytotoxicity. (c) Cytotoxicity evaluation using BT-474 (CD44−) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted. (d) Cytotoxicity evaluation using BT-474EMT (CD44+) cells. CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP curves are plotted.
Mentions: The cytotoxicity of CMHA, nCaPCMHA, CDDP, Aq CDDP, Aq CDDP-CMHA, and nCaPCMHACDDP was examined against BT-474 (CD44 negative) and BT-474EMT (CD44 positive) cells. These studies confirmed that CMHA did not have any inherent toxicity to either cell type (Figure 7(a)). The CMHA stabilized nCaPCMHA also had no cytotoxicity when tested at the concentrations which matched the amount of nCaP in the nCaPCMHACDDP test groups (Figure 7(b)). The IC50 curves of CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP against BT-474 cells are shown in Figure 7(c). The IC50 curves of CDDP, Aq CDDP, and Aq CDDP reacted with CMHA (Aq CDDP-CMHA), and nCaPCMHACDDP against BT-474EMT cells are shown in Figure 7(d). The IC50 values calculated from these curve fits are shown in Table 2. nCaPCMHACDDP and Aq CDDP were significantly more cytotoxic than CDDP alone against BT-474 cells and Aq CDDP-CMHA was significantly less cytotoxic (P ≤ 0.001). nCaPCMHACDDP had comparable cytotoxicity to CDDP against BT-474EMT cells. Aq CDDP-CMHA was significantly less cytotoxic than CDDP (P ≤ 0.001) and Aq CDDP was significantly more cytotoxic (P ≤ 0.05) for BT-474EMT cells.

Bottom Line: CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days.Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP.This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA ; Department of Reconstructive Sciences, UConn Health, Farmington, CT 06030, USA.

ABSTRACT
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(-/low) human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaP(CMHA)CDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaP(CMHA-AF488) was taken up by CD44(+)/CD24(-) BT-474EMT breast cancer cells within 18 hours. nCaP(CMHA)CDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP. This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

No MeSH data available.


Related in: MedlinePlus