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Emerging nanomedicines for anti-stromal therapy against desmoplastic tumors
Xuexiang Han1, Ying Xu1, Marzieh Geranpayehvaghei2
1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, PR China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
Abstract:
Solid tumors, especially desmoplastic tumors, are characterized by a dense fibrotic stroma composed of abundant cancer-associated fibroblasts and excessive extracellular matrix. These physical barriers seriously compromise drug delivery to tumor cells, leading to suboptimal treatment efficacy and resistance to current tumor-centric therapeutics. The need to overcome these problems has driven extensive investigations and sparked the flourish of anti-stromal therapy, particularly in the field of nanomedicines. In this paper, we firstly review the major components of the tumor stroma and discuss their impact on drug delivery. Then, according to the different stromal targets, we summarize the current status of anti-stromal therapy and highlight recent advances in anti-stromal nanomedicines. We further examine the potential of nano-enabled anti-stromal therapy to enhance the anti-tumor efficacy of other therapeutic modalities, including chemotherapy, immunotherapy, phototherapy and radiotherapy. Finally, the potential concerns and future developments of anti-stromal nanomedicines are discussed.
Insights
Solid tumors have dense stroma that blocks cancer drugs. Anti-stromal nanomedicines offer a promising strategy to overcome these barriers and improve treatment efficacy.
Area of Science:
- Oncology
- Nanomedicine
- Biomaterials
Background:
- Solid tumors, particularly desmoplastic types, feature dense fibrotic stroma.
- This stroma, rich in cancer-associated fibroblasts and extracellular matrix, impedes drug delivery.
- Physical barriers in tumors lead to poor treatment outcomes and therapeutic resistance.
Purpose of the Study:
- To review tumor stroma components and their effect on drug delivery.
- To summarize anti-stromal therapies and nanomedicine advancements.
- To explore nano-enabled anti-stromal therapy's potential to enhance multimodal cancer treatments.
Main Methods:
- Literature review of tumor stroma composition and function.
- Analysis of current anti-stromal therapies and nanomedicine strategies.
- Examination of synergistic effects of nano-enabled anti-stromal therapy with chemotherapy, immunotherapy, phototherapy, and radiotherapy.
Main Results:
- Stromal density significantly hinders therapeutic agent penetration.
- Various anti-stromal strategies, especially nanomedicines, are emerging to target tumor microenvironment barriers.
- Nano-enabled anti-stromal approaches show potential to boost efficacy across diverse cancer treatment modalities.
Conclusions:
- Targeting tumor stroma is crucial for improving cancer therapy.
- Nanomedicines represent a key platform for developing effective anti-stromal strategies.
- Further research into anti-stromal nanomedicines is warranted to optimize combination cancer treatments.
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