Polycefin, a new prototype of a multifunctional nanoconjugate based on poly(beta-L-malic acid) for drug delivery.

  title={Polycefin, a new prototype of a multifunctional nanoconjugate based on poly(beta-L-malic acid) for drug delivery.},
  author={Bong-Seop Lee and Manabu Fujita and Natalya M. Khazenzon and Kolja A. Wawrowsky and Sebastian Wachsmann-Hogiu and Daniel L. Farkas and Keith L. Black and Julia Y. Ljubimova and Eggehard Holler},
  journal={Bioconjugate chemistry},
  volume={17 2},
A new prototype of nanoconjugate, Polycefin, was synthesized for targeted delivery of antisense oligonucleotides and monoclonal antibodies to brain tumors. The macromolecular carrier contains: 1. biodegradable, nonimmunogenic, nontoxic beta-poly(L-malic acid) of microbial origin; 2. Morpholino antisense oligonucleotides targeting laminin alpha4 and beta1 chains of laminin-8, which is specifically overexpressed in glial brain tumors; 3. monoclonal anti-transferrin receptor antibody for specific… 

Figures from this paper

Nanoconjugate based on polymalic acid for tumor targeting.
Preparation of poly(β-L-malic acid)-based charge-conversional nanoconjugates for tumor-specific uptake and cellular delivery
The electrostatic interaction between the positively charged HDPEPM nanoconjugates and the negatively charged cell membrane significantly enhanced their cellular uptake, resulting in the enhanced anticancer activity.
Poly(malic acid) nanoconjugates containing various antibodies and oligonucleotides for multitargeting drug delivery.
Delivery of antisense oligonucleotides to a tumor-specific angiogenic marker using Polycefin resulted in significant inhibition of tumor angiogenesis and increase of animal survival.
Functionalization of biodegradable hyperbranched poly(α,β-malic acid) as a nanocarrier platform for anticancer drug delivery
The nanoparticles exhibited an endosomal escape function to accelerate the release of DOX in cancer cells, which resulted in low IC50s to kill 4T1 breast cancer cells and HepG2 liver cancer cells in vitro.
Nanoconjugate Platforms Development Based in Poly(β,L-Malic Acid) Methyl Esters for Tumor Drug Delivery.
Viability of cultured brain and breast cancer cell lines indicated moderate toxicity that increased with methylation and partially methylated poly(β,L-malic acid) copolyesters are suitable as nanoconjugate platforms for drug delivery.
Preparation of Two Types of Polymeric Micelles Based on Poly(β-L-Malic Acid) for Antitumor Drug Delivery
It is suggested that the P2 (crew cut) micelles possess better stability than that of the P1 (star) mouselles and might be a potential drug delivery system for cancer therapy.
Temozolomide Delivery to Tumor Cells by a Multifunctional Nano Vehicle Based on Poly(β-L-malic acid)
TMZ-polymer nanoconjugates entered the tumor cells by receptor-mediated endocytosis, effectively reduced cancer cell viability, and can potentially be used for targeted tumor treatment.
Nanoconjugates of Poly(malic acid) with Functional Modules for Drug Delivery
The nanoconjugates were designed to inhibit tumor growth by preventing angiogenesis and were targeted on the basis of tumor tissue-inherent enhanced permeability and retention (EPR) and antibody recognition.
Design of smart HPMA copolymer-based nanomedicines.
  • Jiyuan Yang, J. Kopeček
  • Biology, Chemistry
    Journal of controlled release : official journal of the Controlled Release Society
  • 2016
Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid)
This work aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid, found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines.


Design of novel bioconjugates for targeted drug delivery.
Novel poly(ethylene glycol) derivatives for preparation of ribosome-inactivating protein conjugates.
Evaluation of the pharmacokinetic behavior of native and PEG-grafted gelonin showed a marked increase in plasma half-life after protein PEGylation; in particular, the circulating life of the conjugates increased with increased molecular weight of the polymer used.
Hemolytic activity of pH-responsive polymer-streptavidin bioconjugates.
The results demonstrate that the PPAAc-streptavidin complex retains the ability to lyse the RBC lipid bilayers at low pHs, such as those existing in endosomes, and the hemolytic ability of the PP AAc-Streptavid in complex is similar to that of the free PPAA c.
Nanogels for oligonucleotide delivery to the brain.
It is demonstrated that as a result of incorporation into nanogel 1 h after intravenous injection the accumulation of a phosphorothioate ODN in the brain increases by over 15 fold while in liver and spleen decreases by 2-fold compared to the free ODN.
A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels
The acid-degradable microgels developed in this article should find applications as delivery vehicles for vaccines targeted against viruses and tumors, where the activation of cytoxic T lymphocytes is required for the development of immunity.
A pH-sensitive polymer that enhances cationic lipid-mediated gene transfer.
The striking enhancement of transfection efficiency with cationic lipid/DNA/PPAA mixtures, along with the enhanced serum-stability, suggests that PPAA may provide significant improvements for the in vivo intracellular delivery of drugs such as DNA, oligonucleotides, proteins, and peptides.