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Supramolecularly-Cross-Linked Nanogel Assemblies for On-Demand, Ultrasound-Triggered Chemotherapy.
Campea, Matthew A; Macdonald, Cameron; Hoare, Todd.
Afiliação
  • Campea MA; Department of Chemical Engineering, McMaster University, Hamilton, ON L8S 4L8, Canada.
  • Macdonald C; Department of Chemical Engineering, McMaster University, Hamilton, ON L8S 4L8, Canada.
  • Hoare T; Department of Chemical Engineering, McMaster University, Hamilton, ON L8S 4L8, Canada.
Biomacromolecules ; 25(8): 4697-4714, 2024 Aug 12.
Article em En | MEDLINE | ID: mdl-38995854
ABSTRACT
Stimulating the release of small nanoparticles (NPs) from a larger NP via the application of an exogenous stimulus offers the potential to address the different size requirements for circulation versus penetration that hinder chemotherapeutic drug delivery. Herein, we report a size-switching nanoassembly-based drug delivery system comprised of ultrasmall starch nanoparticles (SNPs, ∼20-50 nm major size fraction) encapsulated in a poly(oligo(ethylene glycol) methyl ether methacrylate) nanogel (POEGMA, ∼150 nm major size fraction) cross-linked via supramolecular PEG/α-cyclodextrin (α-CD) interactions. Upon heating the nanogel using a non-invasive, high-intensity focused ultrasound (HIFU) trigger, the thermoresponsive POEGMA-CD nanoassemblies are locally de-cross-linked, inducing in situ release of the highly penetrative drug-loaded SNPs. HIFU triggering increased the release of nanoassembly-loaded DOX from 17 to 37% after 3 h, a result correlated with significantly more effective tumor killing relative to nanoassemblies in the absence of HIFU or drug alone. Furthermore, 1.5× more total fluorescence was observed inside a tumor spheroid when nanoassemblies prepared with fluorophore-labeled SNPs were triggered with HIFU relative to the absence of HIFU. We anticipate this strategy holds promise for delivering tunable doses of chemotherapeutic drugs both at and within a tumor site using a non-invasive triggering approach.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article