A liquid immunogenic fiducial eluter for image-guided radiotherapy

Abstract

IntroductionFiducials are routinely used to provide image-guidance during radiotherapy. Here, a new nanoparticle-based liquid immunogenic fiducial is investigated for its potential to provide image-guidance, while also enhancing treatment outcomes.MethodsThis fiducial, liquid immunogenic fiducial eluter (LIFE) biomaterial, is formulated with natural biodegradable polymers, chitosan and sodium alginate with radio-sensitizing nanoparticles, and immunoadjuvant like anti-CD40 monoclonal antibody. Once administered intra-tumorally, this liquid smart radiotherapy biomaterial congeals within the calcium rich tumor microenvironment. The potential use of LIFE biomaterial for providing image guidance in magnetic resonance imaging (MRI) and computed tomography (CT) was investigated over different time period in a pre-clinical tumored mouse model.ResultsResults showed that the LIFE biomaterial can provide both MRI contrast and CT imaging contrast over 3-weeks, with gradual decrease of the contrast over time, as the LIFE biomaterial biodegrades. Results also showed the LIFE biomaterial significantly slowed tumor growth and prolonged mice survival (p < 0.0001) over time.DiscussionThe results highlight the potential use of the LIFE biomaterial as a multi-functional smart radiotherapy biomaterial that could be developed and optimized for hypo-fractionated radiotherapy applications and combining radiotherapy with immunoadjuvants.

Smart Radiotherapy Biomaterials for Image-Guided In Situ Cancer Vaccination

“…The second type of SRB under development is in the form of a liquid fiducial, called liquid immunogenic fiducial eluter (LIFE) Biomaterial [ 28 ]. The LIFE SRB technology is composed of a solution of sodium alginate (ALG) and chitosan that is rapidly transformed into an anchored hydrogel in the presence of calcium ions (Ca 2+ ) within the tumor, illustrated in Figure 3 [ 28 , 29 ].…”

“…The second type of SRB under development is in the form of a liquid fiducial, called liquid immunogenic fiducial eluter (LIFE) Biomaterial [ 28 ]. The LIFE SRB technology is composed of a solution of sodium alginate (ALG) and chitosan that is rapidly transformed into an anchored hydrogel in the presence of calcium ions (Ca 2+ ) within the tumor, illustrated in Figure 3 [ 28 , 29 ]. Immunotherapy drug payloads such as anti-CD40 and/or high-Z nanoparticles such as gold (GNP) or gadolinium nanoparticles can be incorporated into this biodegradable polymer to expand it from single function to multi-functional technology [ 28 ].…”

“…The LIFE SRB technology is composed of a solution of sodium alginate (ALG) and chitosan that is rapidly transformed into an anchored hydrogel in the presence of calcium ions (Ca 2+ ) within the tumor, illustrated in Figure 3 [ 28 , 29 ]. Immunotherapy drug payloads such as anti-CD40 and/or high-Z nanoparticles such as gold (GNP) or gadolinium nanoparticles can be incorporated into this biodegradable polymer to expand it from single function to multi-functional technology [ 28 ]. This enables a potent amount of the immunotherapeutic agent to diffuse locally for a sustained period within the tumor with minimal leakage into neighboring organs.…”

“…This has the potential for extending the role of RT from local palliation to lasting local and distant disease control of metastatic tumors, such as cervical cancer. Preclinical studies have demonstrated that both MRI and CT contrast gradually decrease over the span of 3 weeks, corresponding to the biodegradation of the LIFE biomaterial [ 28 ]. The study also notes significant decrease in tumor progression [ 28 ].…”

“…Preclinical studies have demonstrated that both MRI and CT contrast gradually decrease over the span of 3 weeks, corresponding to the biodegradation of the LIFE biomaterial [ 28 ]. The study also notes significant decrease in tumor progression [ 28 ].…”