We developed a custom-designed liposome carrier for co-delivery of a potent immunogenic cell death (ICD) stimulus plus an inhibitor of the indoleamine 2,3-dioxygenase (IDO-1) pathway to establish a chemo-immunotherapy approach for solid tumors in syngeneic mice. The carrier was constructed by remote import of the anthraquinone chemotherapeutic agent, mitoxantrone (MTO), into the liposomes, which were further endowed with a cholesterol-conjugated indoximod (IND) prodrug in the lipid bilayer. For proof-of-principle testing, we used IV injection of the MTO/IND liposome in a CT26 colon cancer model to demonstrate the generation of a robust immune response, characterized by the appearance of ICD markers (CRT and HMGB-1) as well as evidence of cytotoxic cancer cell death, mediated by perforin and granzyme B. Noteworthy, the cytotoxic effects involved natural killer (NK), which suggests a novel type of ICD response. The immunotherapy response was significantly augmented by co-delivery of the IND prodrug, which induced additional CRT expression, reduced number of Foxp3 + Treg and increased perforin release, in addition to extending animal survival beyond the effect of an MTO-only liposome. The outcome reflects the improved pharmacokinetics of MTO delivery to the cancer site by the carrier.

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Background: Edible plants belonging to the Zingiberaceae family display various antioxidative properties and widely used as folklore medicines. Three edible plants in Zingiberaceae family; namely Boesenbergia rotunda, Phaeomeria imperialis and Zingiber officinale were selected for secondary metabolites extraction using methanol. All crude extracts were investigated to evaluate their phenolics and flavonoids contents and further compare their antioxidant properties. Methods: Total phenolic content and total flavonoid content were evaluated using Folin-Ciocalteu method and Aluminium Complexation Reaction respectively. Conventional DPPH (2,2-diphenyl-1-picryl-hydrazyl), revolutionary CUPRAC (cupric ion reducing antioxidant capacity) and cellular antioxidant activity (CAA) in vitro assays were employed to evaluate the antioxidant activities of methanolic plant extracts for the first time. Results: DPPH and CUPRAC antioxidant assays resulted in similar trend to total flavonoid content in the order Z. officinale >P. imperialis>B. rotunda where as P. imperialis revealed highest phenols content and displayed highest CAA. Conclusion: Methanolic extract of Z. officinale showed highest free radical scavenging ability and hence flavonoids present may potentially act as natural source of antioxidant.

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