Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy

Abstract

Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration. Recent studies have shown that nanoparticle-based therapeutic strategies have more promising applications in improving drug delivery and reversing the immunosuppressive TME for PDAC. Therefore, nanomaterial-based therapeutic approaches are expected to enhance the effectiveness of immunotherapy and improve prognosis of patients with PDAC. Here, we outline the status and dilemma of PDAC immunotherapy, and summarize the latest advances in nanoparticle-based treatment strategies to enhance the efficacy of PDAC immunotherapy.

Systematic review and meta-analysis on safety and efficacy of immune checkpoint inhibitors and radiotherapy for advanced pancreatic cancer

“…In the SBRT studies,103 patients recorded an overall PR of 44% and SBRT + ICI involving 67 patients showed PR of 9%. Wanting Huo et al, described combination of SBRT plus ICIs with ORR of 5.1% (37).Therefore, combining dual ICI therapy with SBRT did not yield a better response. Study on 6 (14%) patients in combination with SBRT and ICIs arm attained a PR, which was confirmed in five patients and lasted for a median of 5.4 months, suggesting durable clinical benefit in some patients with metastatic pancreatic cancer(mPC) with the proposed strategy (29).…”

Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival

“…While PDAC is an inherently immunologically "cold" tumor, and at present, immunotherapy has not proven effective, several alternative and innovative immunotherapy-based strategies have been designed/ proposed to target this tumor [131]. Among them, targeting growth factors and growth factor receptors could be a promising approach for modifying the immunosuppressive TME.…”

Advancing Cancer Treatment Through Nanotechnology Driven Immunotherapy for Pancreatic Cancer

“…Nanotechnology has advanced to the forefront in the fields of therapeutic drug delivery, medical imaging, and diagnostics . The development of nanotechnology to formulate a nanoscale immunotherapeutic system provides the possibilities to enhance the safety and efficacy of cancer immunotherapy because of their excellent pharmacokinetic and biodistribution profiles, including high intratumoral accumulation, deep tumor penetration capacity, and prolonged systemic half-life. − This is due to their unique nanoscale characteristics, including surface area and the quantum effect such as size-dependent optical properties, plasmon resonance, and quantum confinement effects that are typically observed within a size range of 1–100 nm and vary depending upon the material and desired properties. , However, these nanocarrier systems penetrate the tumor via a well-known phenomenon called the enhanced permeability and retention (EPR) effect, resulting from immature and leaky blood vessels .…”