Limits...
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.

Show MeSH

Related in: MedlinePlus

Synthesis of glycine Boc-hydrazide. Reagents and conditions: (i) N,N′-Dicyclohexylcarbodiimide (DCC), Ethyl acetate, 0 °C 2 h, RT 4 h, yield 78%; (ii) H2/Pd-C, MeOH, RT 16 h, yield 80%.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-ijms-13-11681: Synthesis of glycine Boc-hydrazide. Reagents and conditions: (i) N,N′-Dicyclohexylcarbodiimide (DCC), Ethyl acetate, 0 °C 2 h, RT 4 h, yield 78%; (ii) H2/Pd-C, MeOH, RT 16 h, yield 80%.

Mentions: In order to conjugate DOX to a PMLA backbone, the spacer glycine Boc-hydrazide (GBH) was synthesized as illustrated in Scheme I with minor modifications of a method described elsewhere [30]. GBH was obtained by hydrogenolysis of intermediate 3 at atmospheric pressure in the presence of 10% Pd-C in MeOH at room temperature (RT) and recrystallized from ethyl acetate and petroleum ether mixture.


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)

Synthesis of glycine Boc-hydrazide. Reagents and conditions: (i) N,N′-Dicyclohexylcarbodiimide (DCC), Ethyl acetate, 0 °C 2 h, RT 4 h, yield 78%; (ii) H2/Pd-C, MeOH, RT 16 h, yield 80%.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-ijms-13-11681: Synthesis of glycine Boc-hydrazide. Reagents and conditions: (i) N,N′-Dicyclohexylcarbodiimide (DCC), Ethyl acetate, 0 °C 2 h, RT 4 h, yield 78%; (ii) H2/Pd-C, MeOH, RT 16 h, yield 80%.
Mentions: In order to conjugate DOX to a PMLA backbone, the spacer glycine Boc-hydrazide (GBH) was synthesized as illustrated in Scheme I with minor modifications of a method described elsewhere [30]. GBH was obtained by hydrogenolysis of intermediate 3 at atmospheric pressure in the presence of 10% Pd-C in MeOH at room temperature (RT) and recrystallized from ethyl acetate and petroleum ether mixture.

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