An Injectable Composite Co-Assembled Dehydropeptide-Based Magnetic/Plasmonic Lipogel for Multimodal Cancer Therapy

abstract

Advancing therapeutic effectiveness through the strategic co-delivery of drugs in a sequential manner represents a compelling strategy. However, achieving precise and selective release of chemotherapeutic agents remains a formidable challenge. In this study, a co-assembled Arginine-Glycine-Aspartate (RGD)-functionalized dehydropeptide-based gel loaded with magnetic liposomes and mesoporous silica-coated gold nanorods is introduced. This composite system serves as a sophisticated tool to independently modulate the release of doxorubicin and methotrexate. The gel's properties are intricately tuned by the incorporation of liposomes or nanorods and/or the co-assembly with an RGD-functionalized peptide. Furthermore, the combined effects of sequential drug release, photothermia, and magnetic hyperthermia synergistically enhance therapeutic efficacy against 3D cancer cell cultures. Noteworthy attributes of the gel include its ability to orthogonally trigger loaded drugs, along with features such as injectability, rapid gelation, self-healing, and mechanical properties suitable for drug delivery. Consequently, this versatile multimodal platform emerges as a promising option for therapeutic applications, particularly in the context of cancer therapy. A composite co-assembled dehydropeptide-based gel is designed for the orthogonal triggered release of doxorubicin and methotrexate. The incorporation of mesoporous silica-coated gold nanorods and magnetic liposomes within the gel allows for the combined effects of sequential drug release through photothermia and magnetic hyperthermia, resulting in superior therapeutic efficacy against 3D cancer cell cultures. image

keywords

DRUG-DELIVERY; SUPRAMOLECULAR HYDROGELS; RESPONSIVE HYDROGELS; SHORT PEPTIDE; DOXORUBICIN; METHOTREXATE; PACLITAXEL; RELEASE; PH; LIGHT

subject category

Chemistry; Science & Technology - Other Topics; Materials Science; Physics

authors

Veloso, SRS; Vázquez-González, M; Spuch, C; Freiría-Martínez, L; Comís-Tuche, M; Iglesias-Martínez-Almeida, M; Rivera-Baltanás, T; Hilliou, L; Amorim, CO; Amaral, VS; Coutinho, PJG; Ferreira, PMT; Castanheira, EMS; Correa-Duarte, MA

our authors

acknowledgements

This work was funded by Ministerio de Ciencia e Innovacion de Espana (PID2020-113704RB-I00/AEI/10.13039/501100011033; TED2021-132101B-I00/AEI/10.13039/501100011033 and Union Europea "NextGenerationEU"/PRTR), HORIZON-EIC-2022-PATHFINDERCHALLENGES-01-06 and HORIZON-HLTH-2022-DISEASE-06-TWO-STAGE, Xunta de Galicia (Centro Singular de Investigacion de Galicia - Accreditation 2019-2022 ED431G 2019/06 and IN607A 2018/5), Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UIDB/04650/2020), CQUM (UIDB/00686/2020) and CEECINST/00156/2018/CP1642/CT0012. FCT, FEDER, PORTUGAL2020, and COMPETE2020 are also acknowledged for funding under research projects PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020) and PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015). S.R.S.V. acknowledges FCT for a PhD grant (SFRH/BD/144017/2019). Support from the MAP-Fis Doctoral Programme is also acknowledged. M.V.-G. acknowledges support from the Spanish Ministerio de Ciencia e Innovacion under grant IJC2019-040291-I. Funding for open access charge: Universidade de Vigo/CRUE-CISUG.

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