Dataset Information

Dual Aptamer-Functionalized in Situ Injectable Fibrin Hydrogel for Promotion of Angiogenesis via Codelivery of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor-BB.

ABSTRACT: In situ injectable hydrogels hold great potential for in vivo applications such as drug delivery and regenerative medicine. However, it is challenging to ensure stable sequestration and sustained release of loaded biomolecules in these hydrogels. As aptamers have high binding affinities and specificities against target biomolecules, we studied the capability of aptamers in functionalizing in situ injectable fibrin (Fn) hydrogels for in vivo delivery of two growth factors including vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB). The results show that aptamer-functionalized fibrinogen (Fg) could form in situ injectable Fn hydrogels with porous structures. The aptamer-functionalized Fn hydrogels could sequester more VEGF and PDGF-BB than the native Fn and release these growth factors in a sustained manner with high bioactivity. After the aptamer-functionalized Fn hydrogels were subcutaneously injected into mice, the codelivery of VEGF and PDGF-BB could promote the growth of mature blood vessels. Therefore, this study has successfully demonstrated that aptamer-functionalized in situ injectable hydrogels hold great potential for in vivo codelivery of multiple growth factors and promotion of angiogenesis .

SUBMITTER: Zhao N

PROVIDER: S-EPMC6542593 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Dual Aptamer-Functionalized in Situ Injectable Fibrin Hydrogel for Promotion of Angiogenesis via Codelivery of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor-BB.

Zhao Nan N Suzuki Akiho A Zhang Xiaolong X Shi Peng P Abune Lidya L Coyne James J Jia Huizhen H Xiong Na N Zhang Ge G Wang Yong Y

ACS applied materials & interfaces 20190507 20

In situ injectable hydrogels hold great potential for in vivo applications such as drug delivery and regenerative medicine. However, it is challenging to ensure stable sequestration and sustained release of loaded biomolecules in these hydrogels. As aptamers have high binding affinities and specificities against target biomolecules, we studied the capability of aptamers in functionalizing in situ injectable fibrin (Fn) hydrogels for in vivo delivery of two growth factors including vascular endot ...[more]

PMID: 31026135

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Project description:Nanodiamonds (NDs) represent an emerging class of carbon nanomaterials that possess favorable physical and chemical properties to be used as multifunctional carriers for a variety of bioactive molecules. Here we report the synthesis and characterization of a new injectable ND-based nanocomposite hydrogel which facilitates a controlled release of therapeutic molecules for regenerative applications. In particular, we have formulated a thermosensitive hydrogel using gelatin, chitosan and NDs that provides a sustained release of exogenous human vascular endothelial growth factor (VEGF) for wound healing applications. Addition of NDs improved the mechanical properties of the injectable hydrogels without affecting its thermosensitive gelation properties. Biocompatibility of the generated hydrogel was verified by in vitro assessment of apoptotic gene expressions and anti-inflammatory interleukin productions. NDs were complexed with VEGF and the inclusion of this complex in the hydrogel network enabled the sustained release of the angiogenic growth factor. These results suggest for the first time that NDs can be used to formulate a biocompatible, thermosensitive and multifunctional hydrogel platform that can function both as a filling agent to modulate hydrogel properties, as well as a delivery platform for the controlled release of bioactive molecules and growth factors. STATEMENT OF SIGNIFICANCE:One of the major drawbacks associated with the use of conventional hydrogels as carriers of growth factors is their inability to control the release kinetics of the loaded molecules. In fact, in most cases, a burst release is inevitable leading to diminished therapeutic effects and unsuccessful therapies. As a potential solution to this issue, we hereby propose a strategy of incorporating ND complexes within an injectable hydrogel matrix. The functional groups on the surface of the NDs can establish interactions with the model growth factor VEGF and promote a prolonged release from the polymer network, therefore, providing a longer therapeutic effect. Our strategy demonstrates the efficacy of using NDs as an essential component for the design of a novel injectable nanocomposite system with improved release capabilities.

Project description:Despite advances in laparoscopic surgery combined with neoadjuvant and adjuvant therapy, colon cancer management remains challenging in oncology. Recurrence of cancerous tissue locally or in distant organs (metastasis) is the major problem in colon cancer management. Vaccines and immunotherapies hold promise in preventing cancer recurrence through stimulation of the immune system. We and others have shown that nanoparticles from plant viruses, such as cowpea mosaic virus (CPMV) nanoparticles, are potent immune adjuvants for cancer vaccines and serve as immunostimulatory agents in the treatment or prevention of tumors. While being noninfectious toward mammals, CPMV activates the innate immune system through recognition by pattern recognition receptors (PRRs). While the particulate structure of CPMV is essential for prominent immune activation, the proteinaceous architecture makes CPMV subject to degradation in vivo; thus, CPMV immunotherapy requires repeated injections for optimal outcome. Frequent intraperitoneal (IP) injections however are not optimal from a clinical point of view and can worsen the patient's quality of life due to the hospitalization required for IP administration. To overcome the need for repeated IP injections, we loaded CPMV nanoparticles in injectable chitosan/glycerophosphate (GP) hydrogel formulations, characterized their slow-release potential, and assessed the antitumor preventative efficacy of CPMV-in-hydrogel single dose versus soluble CPMV (single and prime-boost administration). Using fluorescently labeled CPMV-in-hydrogel formulations, in vivo release data indicated that single IP injection of the hydrogel formulation yielded a gel depot that supplied intact CPMV over the study period of 3 weeks, while soluble CPMV lasted only for one week. IP administration of the CPMV-in-hydrogel formulation boosted with soluble CPMV for combined immediate and sustained immune activation significantly inhibited colon cancer growth after CT26 IP challenge in BALB/c mice. The observed antitumor efficacy suggests that CPMV can be formulated in a chitosan/GP hydrogel to achieve prolonged immunostimulatory effects as single-dose immunotherapy against colon cancer recurrence. The present findings illustrate the potential of injectable hydrogel technology to accommodate plant virus nanoparticles to boost the translational development of effective antitumor immunotherapies.

Dataset Information

Dual Aptamer-Functionalized in Situ Injectable Fibrin Hydrogel for Promotion of Angiogenesis via Codelivery of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor-BB.

Publications

Dual Aptamer-Functionalized in Situ Injectable Fibrin Hydrogel for Promotion of Angiogenesis via Codelivery of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor-BB.

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