Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
16 04 2019
Historique:
pubmed: 31 3 2019
medline: 9 4 2020
entrez: 31 3 2019
Statut: ppublish

Résumé

Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at sustained therapeutic levels. Here, we report synthesis of porous silicon nanoparticles conjugated with gold nanorods [composite nanoparticles (cNPs)] and encapsulate them within a hybrid polymersome using double-emulsion templates on a microfluidic chip to create a versatile nanovehicle. This nanovehicle has high loading capacities for both hydrophobic and hydrophilic drugs, and improves drug delivery efficiency by accumulating at the tumor after i.v. injection in mice. Importantly, a triple-drug combination suppresses breast tumors by 94% and 87% at total dosages of 5 and 2.5 mg/kg, respectively, through synergy. Moreover, the cNPs retain their photothermal properties, which can be used to significantly inhibit multidrug resistance upon near-infrared laser irradiation. Overall, this work shows that our nanovehicle has great potential as a drug codelivery nanoplatform for effective combination therapy that is adaptable to other cancer types and to molecular targets associated with disease progression.

Identifiants

pubmed: 30926671
pii: 1817251116
doi: 10.1073/pnas.1817251116
pmc: PMC6475426
doi:

Substances chimiques

Antineoplastic Agents 0
Gold 7440-57-5
Silicon Z4152N8IUI

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

7744-7749

Subventions

Organisme : NIBIB NIH HHS
ID : R01 EB023287
Pays : United States

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Hongbo Zhang (H)

Beijing Key Laboratory of Function Materials for Molecule and Structure Construction, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, People's Republic of China.
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Department of Pharmaceutical Sciences Laboratory, Åbo Akademi University, FI-20520 Turku, Finland.
Turku Center for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.

Wenguo Cui (W)

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.

Xiangmeng Qu (X)

Beijing Key Laboratory of Function Materials for Molecule and Structure Construction, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, People's Republic of China.
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Huayin Wu (H)

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Liangliang Qu (L)

Beijing Key Laboratory of Function Materials for Molecule and Structure Construction, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, People's Republic of China.
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Xu Zhang (X)

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Ermei Mäkilä (E)

Laboratory of Industrial Physics, Department of Physics, University of Turku, FI-20014 Turku, Finland.

Jarno Salonen (J)

Laboratory of Industrial Physics, Department of Physics, University of Turku, FI-20014 Turku, Finland.

Yueqi Zhu (Y)

Department of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China; zhuyueqi@hotmail.com mingtanhai@mater.ustb.edu.cn weitz@seas.harvard.edu.

Zhou Yang (Z)

Beijing Key Laboratory of Function Materials for Molecule and Structure Construction, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, People's Republic of China.

Dong Chen (D)

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Hélder A Santos (HA)

Division of Pharmaceutical Chemistry and Technology, Helsinki Institute of Life Science, University of Helsinki, FI-00014 Helsinki, Finland.

Mingtan Hai (M)

Beijing Key Laboratory of Function Materials for Molecule and Structure Construction, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, People's Republic of China; zhuyueqi@hotmail.com mingtanhai@mater.ustb.edu.cn weitz@seas.harvard.edu.
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

David A Weitz (DA)

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; zhuyueqi@hotmail.com mingtanhai@mater.ustb.edu.cn weitz@seas.harvard.edu.
Department of Physics, Harvard University, Cambridge, MA 02138.

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