Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression.
Animals
Antineoplastic Agents
/ administration & dosage
Drug Delivery Systems
/ methods
Female
Gold
Hydrophobic and Hydrophilic Interactions
Mice
Mice, Nude
Microfluidic Analytical Techniques
Nanomedicine
Nanotubes
/ chemistry
Neoplasms, Experimental
/ drug therapy
Photochemical Processes
Porosity
Silicon
cancer therapy
drug delivery
microfluidics
nanomaterials
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
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
7744-7749Subventions
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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