Host-guest complexation-mediated codelivery of anticancer drug and photosensitizer for cancer photochemotherapy.
Animals
Antineoplastic Agents
/ chemical synthesis
Cell Line, Tumor
Click Chemistry
Humans
Mice
Mice, Nude
Nanoparticles
/ chemistry
Neoplasms, Experimental
/ drug therapy
Organoplatinum Compounds
/ chemical synthesis
Photochemotherapy
Photosensitizing Agents
/ chemistry
Porphyrins
/ chemistry
Xenograft Model Antitumor Assays
drug delivery
metallacage
photodynamic therapy
supramolecular coordination complex
theranostic
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:
02 04 2019
02 04 2019
Historique:
pubmed:
22
3
2019
medline:
22
5
2019
entrez:
22
3
2019
Statut:
ppublish
Résumé
Although platinum-based anticancer drugs prevail in cancer treatment, their clinical applications are limited by the severe side effects as well as their ineffectiveness against drug resistant cancers. A precise combination of photodynamic therapy (PDT) and chemotherapy can synergistically improve the therapeutic outcome and thereby may overcome drug resistance through a multipronged assault. Herein, we employ the well-defined cavity of a discrete organoplatinum(II) metallacage (M) to encapsulate octaethylporphine (OEP), a photosensitizer, forming a dual-functionalized system M⊃OEP that is wrapped into the hydrophobic core of the nanoparticles (MNPs) self-assembled from an amphiphilic diblock copolymer. Using a copper-free click reaction, a targeting ligand is conjugated on the surface of the MNPs, aiming to specifically deliver a chemotherapeutic drug and a photosensitizer to cancer cells. Benefiting from the enhanced permeability and retention effect and active targeting capability, high tumor accumulation of MNPs is achieved, leading to an improved therapeutic outcome and reduced side effects. In vivo studies demonstrate that the combination of chemotherapy and PDT exhibits a superior antitumor performance against a drug-resistant tumor model attributed to their synergistic anticancer efficacy.
Identifiants
pubmed: 30894484
pii: 1902029116
doi: 10.1073/pnas.1902029116
pmc: PMC6452736
doi:
Substances chimiques
Antineoplastic Agents
0
Organoplatinum Compounds
0
Photosensitizing Agents
0
Porphyrins
0
octaethylporphyrin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6618-6623Subventions
Organisme : NCI NIH HHS
ID : R01 CA215157
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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