Induction of Immunogenic Cell Death via Nanoparticle-Mediated Dual Chemotherapy and Photothermal Therapy
Date
2020-05
Authors
Aghda, Niloofar Heshmati
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Abstract
Cancer is the second most common cause of mortality in the world. Several treatment modalities have been developed for cancer therapy. Recently, immune checkpoint (ICP) therapy has demonstrated promising results. However, low response rates, cancer recurrence and side effects are remaining problems. In this work, we aimed to develop formulations to enhance the effectiveness of ICP therapy which enables the patient’s immune system to attack cancer cells and, consequently, requires an environment conductive to a targeted immune response against the cancer cells. To achieve this aim, we developed two types of nanoparticles (NPs) for combinatory chemo-photothermal therapy (PTT) to induce immunogenic cell death (ICD) and target the medication to the tumor site. ICD overall causes the activation of dendritic cells (DC) and T cells to initiate an antitumor immune response and is characterized by the presentation of damage associated molecular patterns (DAMPs). NPs were made from biocompatible polymers, poly(lactic acid)-b-poly(ethylene glycol) and bovine serum albumin. Both NPs were loaded with doxorubicin, a chemotherapeutic agent, and indocyanine green, a PTT agent that can absorb the light in near infrared (NIR) region and convert it to heat. NPs were characterized and confirmed to be suitable for agent delivery. Both types of NPs were shown to significantly reduce the viability of model cancer cells, MDA-MB-231 breast cancer cells and B16F10 melanoma cells, in vitro. Analysis of DAMP presentation after treatment demonstrated that NPs could induce ICD. Next, the potential of NP fabrication on a large scale was studied using a high throughput fiber reactor. Poly(lactic-co-glycolic acid) was the polymer used in scale-up studies.
Description
Keywords
Immunogenic cell death, Photothermal therapy, Nanoparticle, Nanomedicine, Fiber reactor, Indocyanine green, Doxorubicin, Albumin, Poly(lactic-co-glycolic acid), NIR laser, Damage-associated molecular patterns, DAMP, ICD, PTT
Citation
Aghda, N. H. (2020). Induction of immunogenic cell death via nanoparticle-mediated dual chemotherapy and photothermal therapy (Unpublished dissertation). Texas State University, San Marcos, Texas.