Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Aug 18;53(34):8975-9.
doi: 10.1002/anie.201404766. Epub 2014 Jul 2.

Development of multinuclear polymeric nanoparticles as robust protein nanocarriers

Jun Wu  1 , Nazila Kamaly, Jinjun Shi, Lili Zhao, Zeyu Xiao, Geoffrey Hollett, Rohit John, Shaunak Ray, Xiaoyang Xu, Xueqing Zhang, Philip W Kantoff, Omid C Farokhzad
Affiliations

Development of multinuclear polymeric nanoparticles as robust protein nanocarriers

Jun Wu et al. Angew Chem Int Ed Engl. .

Abstract

One limitation of current biodegradable polymeric nanoparticles is their inability to effectively encapsulate and sustainably release proteins while maintaining protein bioactivity. Here we report the engineering of PLGA-polycation nanoparticles with a core-shell structure that act as a robust vector for the encapsulation and delivery of proteins and peptides. The optimized nanoparticles can load high amounts of proteins (>20 % of nanoparticles by weight) in aqueous solution without organic solvents through electrostatic interactions by simple mixing, thereby forming nanospheres in seconds with diameters <200 nm. The relationship between nanosphere size, surface charge, PLGA-polycation composition, and protein loading is also investigated. The stable nanosphere complexes contain multiple PLGA-polycation nanoparticles, surrounded by large amounts of protein. This study highlights a novel strategy for the delivery of proteins and other relevant molecules.

Keywords: nanoparticles; polycations; polymers; protein delivery; structure-function relationships.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Illustration of the synthesis of PLGA-b-polycation (PC) copolymer, PLGA-PC NP, PLGA-PC/Protein NP, PLGA-PC/Protein/Lipid-PEG NP, and the multinuclear structure of NP.
Figure 2
Figure 2
Synthesis of L-arginine–based PC (1) and PLGA-b-PC copolymer (2)
Figure 3
Figure 3
TEM images of PLGA-PC NPs (a)PLGA2-PC16; (b) PLGA1-PC16; (c) illustration of PLGA-PC composition effect (by changing PLGA portion) on nanoparticle size; (d) Particle size of PLGA-PC and PLGA NPs from DLS.
Figure 4
Figure 4
TEM images of PLGA-PC/Protein nanoparticles (a-d): (a) PLGA2-PC 16 with 2 wt% BSA loading; (b-d) PLGA2-PC16 with 25 wt% BSA loading. Structure-function relationship among the zeta potential, particle size, and weight ratio of PLGA-PC/BSA complex particle (e-f)
Figure 5
Figure 5
(A) and (B), TEM image and release profile of PLGA2-PC16 NP/BSA/DSPE–PEG3000; (C) and (D), the cellular uptake of fluorescence BSA (c) and PLGA2-PC16 NP/fluorescence BSA / DSPE–PEG3000 (d) after 4 hours.
See this image and copyright information in PMC

References

    1. Langer R, Tirrell DA. Nature. 2004;428:487. - PubMed
    1. Gu Z, Biswas A, Zhao M, Tang Y. Chemical Society Reviews. 2011;40:3638. - PubMed
    1. Vermonden T, Censi R, Hennink WE. Chemical Reviews. 2012;112:2853. - PubMed
    1. Kamaly N, Fredman G, Subramanian M, Gadde S, Pesic A, Cheung L, Fayad ZA, Langer R, Tabas I, Cameron Farokhzad O. Proceedings of the National Academy of Sciences. 2013;110:6506. - PMC - PubMed
    1. Yan M, Du J, Gu Z, Liang M, Hu Y, Zhang W, Priceman S, Wu L, Zhou ZH, Liu Z, Segura T, Tang Y, Lu Y. Nat Nano. 2010;5:48. - PubMed

Publication types