Dual-Crosslinked Dynamic Hydrogel Incorporating {Mo-154} with pH and NIR Responsiveness for Chemo-Photothermal Therapy

abstract

Polyoxometalates are an emerging class of molecular clusters, with well-defined structures and chemical compositions that are produced through simple, low-cost, and highly reproducible methods. In particular, the wheel-shaped cluster {Mo-154} is a promising photothermal agent due to its intervalence charge transfer transitions. However, its toxicity hinders its systemic administration, being the development of a localized delivery system still incipient. Herein, an injectable and self-healing hydrogel of easy preparation and administration is developed, incorporating both {Mo-154} and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel is composed of benzylaldehyde functionalized polyethylene glycol, poly(N-isopropylacrylamide) functionalized chitosan and {Mo-154}. The gelation occurs within 60 s at room temperature, and the dual crosslinking by Schiff base and electrostatic interactions generates a dynamic network, which enables self-healing after injection. Moreover, the hydrogel delivers chemotherapeutic drugs, with a release triggered by dual near infra-red (NIR) radiation and pH changes. This stimuli-responsive release system along with the photothermal conversion ability of the hydrogel allows the simultaneous combination of photothermal and chemotherapy. This synergic system efficiently ablates the cancer tumor in vivo with no systemic toxicity. Overall, this work paves the way for the development of novel {Mo-154}-based systems, incorporated in self-healing and injectable hydrogels for dual chemo-photothermal therapy.

keywords

DRUG-DELIVERY; POLYOXOMETALATE CLUSTER; INJECTABLE HYDROGELS; THERMO-CHEMOTHERAPY; CANCER; NANOCOMPOSITE; CHITOSAN

subject category

Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter

authors

Guedes, G; Wang, SQ; Fontana, F; Figueiredo, P; Linden, J; Correia, A; Pinto, RJB; Hietala, S; Sousa, FL; Santos, HA

Groups

G2 - Photonic, Electronic and Magnetic Materials
G4 - Renewable Materials and Circular Economy

Projects

Multidimensional thermal rectifiers based on assembly of anisotropic polyoxometalates (THERMOPOMs)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

acknowledgements

G.G., S.W., and F.F. contributed equally to this work. Dr. Shiqi Wang acknowledges the financial support from Finnish Culture Foundation (grant no. 00201144) and from Academy of Finland (decision no. 331106). Prof. Santos acknowledges the financial support from the HiLIFE Research Funds, the Sigrid Juselius Foundation, the Academy of Finland (grant nos. 317042 and 331151), and the European Research Council Proof-of-Concept Research Grant (grant no. 825020). The authors thank JoAo Pedro Martins for making the video in the Supporting Information. The authors also thank Jiachen Li and Heikki Raikkonen for the support of setting up the laser. The work performed in Aveiro was developed within the scope of the projects ThermoPOMs P2020-PTDC-QEQ-QIN-5975-2014 and CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. F.L.S. acknowledges FCT for the IF/01533/2015 grant.