DOI: 10.1073/pnas.0711714105. Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers

Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers

10.1073/pnas.0711714105

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

There has been progressively heightened interest in the development of targeted nanoparticles (NPs) for differential delivery and controlled release of drugs. Despite nearly three decades of research, approaches to reproducibly formulate targeted NPs with the optimal biophysicochemical properties have remained elusive. A central challenge has been defining the optimal interplay of parameters that confer molecular targeting, immune evasion, and drug release to overcome the physiological barriers in vivo . Here, we report a strategy for narrowly changing the biophysicochemical properties of NPs in a reproducible manner, thereby enabling systematic screening of optimally formulated drug-encapsulated targeted NPs. NPs were formulated by the self-assembly of an amphiphilic triblock copolymer composed of end-to-end linkage of poly(lactic-co-glycolic-acid) (PLGA), polyethyleneglycol (PEG), and the A10 aptamer (Apt), which binds to the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer (PCa) cells, enabling, respectively, controlled drug release, “stealth” properties for immune evasion, and cell-specific targeting. Fine-tuning of NP size and drug release kinetics was further accomplished by controlling the copolymer composition. By using distinct ratios of PLGA- b -PEG- b -Apt triblock copolymer with PLGA- b -PEG diblock copolymer lacking the A10 Apt, we developed a series of targeted NPs with increasing Apt densities that inversely affected the amount of PEG exposure on NP surface and identified the narrow range of Apt density when the NPs were maximally targeted and maximally stealth, resulting in most efficient PCa cell uptake in vitro and in vivo . This approach may contribute to further development of targeted NPs as highly selective and effective therapeutic modalities.

Bibliography

Gu, F., Zhang, L., Teply, B. A., Mann, N., Wang, A., Radovic-Moreno, A. F., Langer, R., & Farokhzad, O. C. (2008). Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proceedings of the National Academy of Sciences, 105(7), 2586â2591.

Authors 8

Frank Gu (first)
Liangfang Zhang (additional)
Benjamin A. Teply (additional)
Nina Mann (additional)
Andrew Wang (additional)
Aleksandar F. Radovic-Moreno (additional)
Robert Langer (additional)
Omid C. Farokhzad (additional)

References 27 Referenced 599

R Langer, Drug delivery and targeting. Nature 392, 5–10 (1998). / Nature / Drug delivery and targeting. by Langer R (1998)
10.1073/pnas.0601755103
M Ferrari, Cancer nanotechnology: Opportunities and challenges. Nature Rev 5, 161–171 (2005). / Nature Rev / Cancer nanotechnology: Opportunities and challenges. by Ferrari M (2005)
10.1016/S1748-0132(07)70083-X
10.1016/j.addr.2006.09.011
10.1126/science.7423203
10.1038/288602a0
L Zhang, et al., Nanoparticles in medicine: Therapeutic applications and developments. Clin Pharmacol Ther, 2007). / Clin Pharmacol Ther / Nanoparticles in medicine: Therapeutic applications and developments. by Zhang L (2007)
10.1021/bc020089t
10.1021/bc050113d
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SE Lupold, BJ Hicke, Y Lin, DS Coffey, Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res 62, 4029–4033 (2002). / Cancer Res / Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. by Lupold SE (2002)
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10.1038/nbt1223
10.1158/0008-5472.CAN-05-4583
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10.1126/science.8128245

Dates

Type	When
Created	17 years, 6 months ago (Feb. 13, 2008, 8:59 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:20 p.m.)
Indexed	1 day, 16 hours ago (Aug. 30, 2025, 12:20 p.m.)
Issued	17 years, 6 months ago (Feb. 19, 2008)
Published	17 years, 6 months ago (Feb. 19, 2008)
Published Online	17 years, 6 months ago (Feb. 19, 2008)
Published Print	17 years, 6 months ago (Feb. 19, 2008)

Funders 0

None

BibTeX

@article{Gu_2008, title={Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers}, volume={105}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0711714105}, DOI={10.1073/pnas.0711714105}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Gu, Frank and Zhang, Liangfang and Teply, Benjamin A. and Mann, Nina and Wang, Andrew and Radovic-Moreno, Aleksandar F. and Langer, Robert and Farokhzad, Omid C.}, year={2008}, month=feb, pages={2586–2591} }

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  "abstract": "<jats:p>\n            There has been progressively heightened interest in the development of targeted nanoparticles (NPs) for differential delivery and controlled release of drugs. Despite nearly three decades of research, approaches to reproducibly formulate targeted NPs with the optimal biophysicochemical properties have remained elusive. A central challenge has been defining the optimal interplay of parameters that confer molecular targeting, immune evasion, and drug release to overcome the physiological barriers\n            <jats:italic>in vivo</jats:italic>\n            . Here, we report a strategy for narrowly changing the biophysicochemical properties of NPs in a reproducible manner, thereby enabling systematic screening of optimally formulated drug-encapsulated targeted NPs. NPs were formulated by the self-assembly of an amphiphilic triblock copolymer composed of end-to-end linkage of poly(lactic-co-glycolic-acid) (PLGA), polyethyleneglycol (PEG), and the A10 aptamer (Apt), which binds to the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer (PCa) cells, enabling, respectively, controlled drug release, \u201cstealth\u201d properties for immune evasion, and cell-specific targeting. Fine-tuning of NP size and drug release kinetics was further accomplished by controlling the copolymer composition. By using distinct ratios of PLGA-\n            <jats:italic>b</jats:italic>\n            -PEG-\n            <jats:italic>b</jats:italic>\n            -Apt triblock copolymer with PLGA-\n            <jats:italic>b</jats:italic>\n            -PEG diblock copolymer lacking the A10 Apt, we developed a series of targeted NPs with increasing Apt densities that inversely affected the amount of PEG exposure on NP surface and identified the narrow range of Apt density when the NPs were maximally targeted and maximally stealth, resulting in most efficient PCa cell uptake\n            <jats:italic>in vitro</jats:italic>\n            and\n            <jats:italic>in vivo</jats:italic>\n            . This approach may contribute to further development of targeted NPs as highly selective and effective therapeutic modalities.\n          </jats:p>",
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