Abstract
Ratiometric delivery of combination chemotherapy can achieve therapeutic efficacy based on synergistic interactions between drugs. It is critical to design such combinations with drugs that complement each other and reduce cancer growth through multiple mechanisms. Using hyaluronic acid (HA) as a carrier, two chemotherapeutic agents—doxorubicin (DOX) and camptothecin (CPT)—were incorporated and tested for their synergistic potency against a broad panel of blood-cancer cell lines. The pair also demonstrated the ability to achieve immunogenic cell death by increasing the surface exposure levels of Calreticulin, thereby highlighting its ability to induce apoptosis via an alternate pathway. Global proteomic profiling of cancer cells treated with HA–DOX–CPT identified pathways that could potentially predict patient sensitivity to HA–DOX–CPT. This lays the foundation for further exploration of integrating drug delivery and proteomics in personalized immunogenic chemotherapy.
Highlights
Academic Editor: Wei HuangCombination chemotherapy has played an active role in treating blood cancers such as acute myeloid leukemia (AML) and T-cell lymphoma (TCL)
Our proteomic studies in blood-cancer cells have revealed multiple candidates that might serve as biomarkers of prognosis and drug resistance
These findings can be utilized as a resource to guide the design of combination drug delivery while identifying mechanisms or pathways that promote multi-drug resistance and promote enhanced therapeutic efficacy
Summary
Academic Editor: Wei HuangCombination chemotherapy has played an active role in treating blood cancers such as acute myeloid leukemia (AML) and T-cell lymphoma (TCL). Over the past couple of decades, significant effort has gone into understanding the biological basis of blood cancers. This accelerated the development and use of drug cocktails in clinical oncology [1,2,3,4,5,6,7,8,9]. To achieve target cell accumulation of synergistic drug combinations, it is vital to maintain control over the differential pharmacokinetics, distribution, and metabolism of each drug following its systemic delivery in vivo. In addition to applications in multimodal in vivo imaging for disease diagnosis or single-drug delivery, nanotechnology can be used to achieve the ratiometric delivery of Received: 19 December 2021
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