Extensive Review of Nanomedicine Strategies Targeting the Tumor Microenvironment in PDAC

Mar 24, 2025International journal of nanomedicine

Nanomedicine Approaches Targeting the Surrounding Environment of Pancreatic Cancer Tumors

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is associated with significant challenges in effective treatment due to its complex .

The tumor microenvironment in PDAC promotes tumor progression and metastasis through a dense connective tissue matrix and immune suppression.
Traditional therapies, including surgery, chemotherapy, and radiation, are limited by the tumor's location, the dense extracellular matrix, and the immunosuppressive environment.
Nanoscale drug delivery systems (NDDSs) offer potential benefits, such as improved drug stability, enhanced tumor penetration, and reduced systemic toxicity.
Challenges for the clinical application of NDDSs in PDAC include the need for targeted drug delivery, control over drug release, and addressing potential immune responses.
Current strategies in TME-targeted therapy show promise but also highlight limitations and the need for future research to overcome these challenges.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world, mainly because of its powerful pro-connective tissue proliferation matrix and immunosuppressive (TME), which promote tumor progression and metastasis. In addition, the extracellular matrix leads to vascular collapse, increased interstitial fluid pressure, and obstruction of lymphatic return, thereby hindering effective drug delivery, deep penetration, and immune cell infiltration. Therefore, reshaping the TME to enhance tumor perfusion, increase deep drug penetration, and reverse immune suppression has become a key therapeutic strategy. Traditional therapies for PDAC, including surgery, radiation, and chemotherapy, face significant limitations. Surgery is challenging due to tumor location and growth, while chemotherapy and radiation are hindered by the dense extracellular matrix and immunosuppressive TME. In recent years, the advancement of nanotechnology has provided new opportunities to improve drug efficacy. Nanoscale drug delivery systems (NDDSs) provide several advantages, including improved drug stability in vivo, enhanced tumor penetration, and reduced systemic toxicity. However, the clinical translation of nanotechnology in PDAC therapy faces several challenges. These include the need for precise targeting and control over drug release, potential immune responses to the nanocarriers, and the scalability and cost-effectiveness of production. This article provides an overview of the latest nanobased methods for achieving better therapeutic outcomes and overcoming drug resistance. We pay special attention to TME-targeted therapy in the context of PDAC, discuss the advantages and limitations of current strategies, and emphasize promising new developments. By emphasizing the enormous potential of NDDSs in improving the treatment outcomes of patients with PDAC, while critically discussing the limitations of traditional therapies and the challenges faced by nanotechnology in achieving clinical breakthroughs, our review paves the way for future research in this rapidly developing field.

Key numbers

66,440

Projected New Cases

Estimated new PDAC cases in the U.S. for 2024.

6.1 months

Survival Extension

Average survival with Onivyde plus 5-FU and leucovorin.

90%

Transferrin Receptor Overexpression

Percentage of malignant pancreatic cancer cells overexpressing transferrin receptors.

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Abstract

Key numbers

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