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Cellular delivery of doxorubicin via pH-controlled hydrazone linkage using multifunctional nano vehicle based on poly(β-l-malic acid).

Patil R, Portilla-Arias J, Ding H, Konda B, Rekechenetskiy A, Inoue S, Black KL, Holler E, Ljubimova JY - Int J Mol Sci (2012)

Bottom Line: Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems.This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid.DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.

View Article: PubMed Central - PubMed

Affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA; E-Mails: portillaj@cshs.org (J.P.-A.); dinghx@cshs.org (H.D.); kondab@cshs.org (B.K.); rekechenetskiya@cshs.org (A.R.); inoues@cshs.org (S.I.); blackk@cshs.org (K.L.B.); ljubimovaj@cshs.org (J.Y.L.).

ABSTRACT
Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β-l-malic acid) (PMLA). DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.

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Related in: MedlinePlus

Effect of nanoconjugate P/PEG(5%)/GH-DOX(5%), P/PEG(5%)/GH(5%) and free DOX on cell viability of human breast cancer cell lines MDA-MB-231, MDA-MB-468 and human glioma cell lines U87MG, U251. The concentrations refer to DOX content.
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f4-ijms-13-11681: Effect of nanoconjugate P/PEG(5%)/GH-DOX(5%), P/PEG(5%)/GH(5%) and free DOX on cell viability of human breast cancer cell lines MDA-MB-231, MDA-MB-468 and human glioma cell lines U87MG, U251. The concentrations refer to DOX content.

Mentions: The effects of nanoconjugate P/PEG(5%)/GH-DOX(5%) on cell viability of invasive breast carcinoma cells MDA-MB-231 and MDA-MB-468, and on human glioma cells U87MG and U251 was measured. The degree of inhibition of cell viability was compared with that of free DOX and of the carrier nanoconjugate P/PEG(5%)/GH(5%) without DOX (Figure 4). IC50 values are summarized in Table 2. The results indicated that the inhibition by nanoconjugate P/PEG(5%)/GH-DOX(5%) followed a dose dependant response similarly to that of free DOX, but was shifted towards 2 to 3 fold higher concentrations in the case of cell lines MDAMB-231, MDAMB-468 and U87MG, and was shifted towards lower concentrations in the case of DOX-resistant glioma cell line U251.


Cellular delivery of doxorubicin via pH-controlled hydrazone linkage using multifunctional nano vehicle based on poly(β-l-malic acid).

Patil R, Portilla-Arias J, Ding H, Konda B, Rekechenetskiy A, Inoue S, Black KL, Holler E, Ljubimova JY - Int J Mol Sci (2012)

Effect of nanoconjugate P/PEG(5%)/GH-DOX(5%), P/PEG(5%)/GH(5%) and free DOX on cell viability of human breast cancer cell lines MDA-MB-231, MDA-MB-468 and human glioma cell lines U87MG, U251. The concentrations refer to DOX content.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472769&req=5

f4-ijms-13-11681: Effect of nanoconjugate P/PEG(5%)/GH-DOX(5%), P/PEG(5%)/GH(5%) and free DOX on cell viability of human breast cancer cell lines MDA-MB-231, MDA-MB-468 and human glioma cell lines U87MG, U251. The concentrations refer to DOX content.
Mentions: The effects of nanoconjugate P/PEG(5%)/GH-DOX(5%) on cell viability of invasive breast carcinoma cells MDA-MB-231 and MDA-MB-468, and on human glioma cells U87MG and U251 was measured. The degree of inhibition of cell viability was compared with that of free DOX and of the carrier nanoconjugate P/PEG(5%)/GH(5%) without DOX (Figure 4). IC50 values are summarized in Table 2. The results indicated that the inhibition by nanoconjugate P/PEG(5%)/GH-DOX(5%) followed a dose dependant response similarly to that of free DOX, but was shifted towards 2 to 3 fold higher concentrations in the case of cell lines MDAMB-231, MDAMB-468 and U87MG, and was shifted towards lower concentrations in the case of DOX-resistant glioma cell line U251.

Bottom Line: Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems.This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid.DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.

View Article: PubMed Central - PubMed

Affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA; E-Mails: portillaj@cshs.org (J.P.-A.); dinghx@cshs.org (H.D.); kondab@cshs.org (B.K.); rekechenetskiya@cshs.org (A.R.); inoues@cshs.org (S.I.); blackk@cshs.org (K.L.B.); ljubimovaj@cshs.org (J.Y.L.).

ABSTRACT
Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β-l-malic acid) (PMLA). DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.

Show MeSH
Related in: MedlinePlus